natriuretic-peptide--brain and Aortic-Valve-Stenosis

This review summarizes the current management of patients with newly diagnosed aortic stenosis.. Recent developments include detection of early myocardial dysfunction using serum B-type natriuretic peptide levels and global longitudinal strain, as well as ongoing trials of transcatheter aortic valve replacement in asymptomatic patients and patients with moderate aortic stenosis complicated by symptoms or left ventricular systolic dysfunction. Given the high mortality associated with severe symptomatic aortic stenosis, all symptomatic patients should be referred for aortic valve replacement. Asymptomatic patients with left ventricular systolic dysfunction, abnormal exercise stress test, high degree of stenosis, rapid disease progression, or elevated serum B-type natriuretic peptide level may also have an indication for valve replacement, based on established criteria. The progress in management of severe aortic stenosis has been in the direction of earlier detection and earlier valve replacement.

Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Risk Assessment; Severity of Illness Index; Ventricular Dysfunction, Left

Serum biomarkers have a potential role in the risk stratification of patients with heart valve disease and may help determine the optimal timing of intervention. Much of the published literature relates to biomarker sampling in a resting state, but the relationship of exercise biomarkers is less well described. We performed a systematic review to examine the significance of exercise natriuretic peptides on echocardiographic variables and cardiovascular events, in valvular heart disease.. A search for studies that assessed exercise biomarkers in patients with moderate to severe valve lesions was performed. We examined the relationship between rest and exercise BNP and also the endpoints of symptoms, haemodynamic or echocardiographic variables and clinical outcomes.. Eleven prospective studies were identified (844 participants). 61% were male and the mean age was 55.2 ± 9.6 years. The majority of the blood samples were taken at baseline and within 3 minutes of stopping exercise. There was a significant increase in exercise BNP compared with rest, in patients with aortic stenosis, mitral regurgitation and mitral stenosis. Elevated exercise BNP levels correlated with mean gradient and left atrial area, and there was a relationship between a higher exercise BNP and a blunted blood pressure response, in aortic stenosis. Furthermore, exercise BNP was independently associated with cardiac events, over and above resting values, in patients with mitral regurgitation and aortic stenosis.. The results suggesting that exercise natriuretic peptide levels may have additive prognostic importance over resting levels, as well as demographic and echocardiographic data.

Topics: Aortic Valve Stenosis; Biomarkers; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Natriuretic Peptides; Prospective Studies

The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95-3.44;

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Galectin 3; Humans; Natriuretic Peptide, Brain; Troponin

We performed a meta-analysis of currently available studies investigating impact of baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality after transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS). MEDLINE and EMBASE were searched through August 2018 using PubMed and OVID. Studies considered for inclusion met the following criteria: the design was a study researching impact of baseline NT-proBNP levels on survival; the study population was patients underwent TAVI for AS; outcomes included all-cause mortality. For each study, we directly extracted odds ratio (ORs) or hazard ratios (HRs) of mortality (for high vs low baseline NT-proBNP); and generated ORs using mortality rates in both patients with high and low levels of baseline NT-proBNP. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic ORs/HRs in the random-effects model. We identified 16 eligible studies including a total of 3,679 patients who underwent TAVI for AS. Pooled analyses demonstrated that high levels of baseline NT-proBNP were associated with a statistically nonsignificant increase in early (30-day or 2-month) mortality (pooled OR, 1.60; 95% confidence interval, 0.84 to 3.04; p = 0.15) and a statistically significant increase in midterm (6-month to 4-year) mortality (pooled OR/HR, 1.88; 95% confidence interval, 1.54 to 2.28; p < 0.00001). Although funnel-plot asymmetry suggesting publication bias was detected, adjusting for funnel-plot asymmetry indicated an association of high levels of baseline NT-proBNP with a still significant increase in midterm mortality. In conclusion, high levels of baseline NT-proBNP predict increased midterm, not early, mortality after TAVI for AS.

Topics: Aortic Valve Stenosis; Biomarkers; Global Health; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Protein Precursors; Risk Factors; Survival Rate; Transcatheter Aortic Valve Replacement

The purpose of this review is to outline the relationship between serum biomarkers of cardiac stress and the pathophysiologic progression of aortic stenosis, to identify studies exploring the utility of biomarkers in the risk stratification and management of patients with aortic stenosis, and to highlight the biomarkers most practical to management of patients with aortic stenosis.. Several biomarkers have been identified that reflect various aspects of the pathogenesis of calcific aortic stenosis, subsequent hemodynamic obstruction leading to myocardial remodeling, oxidative stress and injury, and concomitant systemic inflammation. These markers are associated with adverse outcomes in aortic stenosis and offer incremental value in risk prediction over traditional clinical assessment for aortic stenosis. NTproBNP and troponin are the most rigorously studied serum biomarkers in aortic stenosis, and only NTproBNP is currently reflected in any major guideline on aortic stenosis management. Serum biomarkers show promise in guiding management of aortic stenosis, but still require significant prospective investigation before they can be incorporated in major guidelines.

Topics: Aortic Valve Stenosis; Biomarkers; Cardiac Imaging Techniques; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Severity of Illness Index

Aortic stenosis is the most common primary valve problem. This article describes its assessment and clinical interpretation using echocardiography and also shows how magnetic resonance, cardiac computed tomography and stress testing may be useful.

Topics: Aortic Valve Stenosis; Cardiac Catheterization; Coronary Angiography; Echocardiography; Exercise Test; Heart Valve Prosthesis Implantation; Humans; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Severity of Illness Index; Tomography, X-Ray Computed

Aortic stenosis (AS) is one of the most common valvular diseases encountered in clinical practice. Current guidelines recommend aortic valve replacement (AVR) when the aortic valve is severely stenotic and the patient is symptomatic; however, a substantial proportion of patients with severe AS are asymptomatic at the time of first diagnosis. Although specific morphological valve features, exercise testing, stress imaging, and biomarkers can help to identify patients with asymptomatic severe AS who may benefit from early AVR, the optimal management of these patients remains uncertain and controversial. The current report presents a comprehensive review of the natural history and the diagnostic evaluation of asymptomatic patients with severe AS, and is followed by a meta-analysis from reported studies comparing an early AVR strategy to active surveillance, with an emphasis on the level of evidence substantiating the current guideline recommendations. Finally, perspectives on directions for future investigation are discussed.

Topics: Aortic Valve; Aortic Valve Stenosis; Asymptomatic Diseases; Biomarkers; Conservative Treatment; Death, Sudden; Diagnostic Imaging; Disease Progression; Echocardiography, Stress; Exercise Test; Heart Valve Prosthesis; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Severity of Illness Index; Stroke Volume

Topics: Aortic Valve Stenosis; Asymptomatic Diseases; Humans; Hypertrophy, Left Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Ventricular Pressure

The optimal timing of valve surgery remains controversial. Biomarkers can be serially monitored and are objective laboratory measurements. Plasma B-type natriuretic peptide (BNP) and its N-terminal pro-form are well known predictors in heart failure. Diastolic stretch induces cardiomyocyte BNP expression in volume-loaded conditions like aortic or mitral regurgitation (MR) or pressure-loaded conditions like aortic stenosis (AS). Here, we review the value of natriuretic peptide measurements in valve disease. Cardiac decompensation is reflected by increased BNP in AS and in MR. Repeated marked increases in natriuretic peptides are a potential indication for valve replacement in severe asymptomatic AS with normal ejection fraction and exercise test results. High BNP level also predicts postoperative outcome. Increased BNP level is associated with low-flow AS, impaired left ventricular longitudinal strain, and myocardial fibrosis. The BNP ratio to the reference value for age and sex incrementally predicts mortality in AS. Increased BNP reflects the hemodynamic consequences of MR and is associated with exercise-induced pulmonary-arterial hypertension and reduced contractile reserve. In severe primary MR, increased and serially increasing BNP or N-terminal pro-form BNP might be helpful in guiding early mitral replacement. In conclusion, baseline (N-terminal pro-form) BNP should be obtained in all severe valve disease patients and interpreted together with clinical and echocardiography findings. Very high BNP values are associated with increased mortality and should lead to close monitoring peri- and postoperatively. Progressively increasing BNP in asymptomatic patients points to advancing valve disease. BNP adds important incremental prognostic information that is useful for valve patient management and for optimal timing of surgery in particular.

Topics: Age Factors; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Female; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Male; Mitral Valve Insufficiency; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Sex Factors; Tricuspid Valve Insufficiency

Topics: Age Factors; Almanacs as Topic; Aortic Valve Insufficiency; Aortic Valve Stenosis; Austria; Biomarkers; Biomedical Research; Cardiac Surgical Procedures; Cardiology; Endocarditis; Fluorobenzenes; Heart Valve Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Mitral Valve Insufficiency; Natriuretic Agents; Natriuretic Peptide, Brain; Periodicals as Topic; Prevalence; Prognosis; Pyrimidines; Randomized Controlled Trials as Topic; Risk Factors; Rosuvastatin Calcium; Severity of Illness Index; Smoking; Sulfonamides; Tricuspid Valve Insufficiency

Valvular heart disease remains common in industrialized countries, because the decrease in prevalence of rheumatic heart diseases has been accompanied by an increase in that of degenerative valve diseases. Aortic stenosis and mitral regurgitation are the two most common types of valvular disease in Europe. The prevalence of valvular disease increases sharply with age, owing to the predominance of degenerative etiologies. The burden of heart valve disease in the elderly has an important impact on patient management, given the high frequency of comorbidity and the increased risk associated with intervention in this age group. Endocarditis is an important etiology of valvular disease and is most commonly caused by Staphylococci. Rheumatic heart disease remains prevalent in developing countries.

Topics: Adult; Age Factors; Aortic Valve; Aortic Valve Stenosis; Disease Progression; France; Global Health; Heart Valve Diseases; Humans; Mitral Valve; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Ultrasonography

B-type natriuretic peptide (BNP) and its prohormone NT-proBNP are released in response to myocardial wall stress and are established predictors of outcome in heart failure. This article discusses the prognostic value of BNP in aortic stenosis (AS). In recent studies, BNP and NT-proBNP were consistently related to AS severity and symptom status. High or serially rising BNP predicted the short-term need for valve replacement in asymptomatic severe AS. Preoperative BNP or NT-proBNP reflected postoperative outcome. In low-flow low-gradient AS, high BNP greater than 550 pg/mL predicted poor outcome independently of contractile reserve. BNP and NT-proBNP are easy to assess from plasma and improve risk stratification in the whole spectrum of AS.

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Heart Valve Prosthesis Implantation; Heart Ventricles; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Severity of Illness Index; Ventricular Function, Left

Topics: Aged; Aortic Valve Stenosis; Blood Gas Analysis; Cardiotonic Agents; Diagnosis, Differential; Female; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Lymphoma, Non-Hodgkin; Natriuretic Peptide, Brain; Nurse Practitioners; Nurse's Role; Nursing Assessment; Oncology Nursing; Oxygen Inhalation Therapy; Risk Factors; Vasodilator Agents

Aortic valve diseases, namely aortic stenosis (AS) and aortic regurgitation (AR), are common in developed countries with AS being the most common valvular heart disease. Symptomatic status and echocardiography are the most important clinical parameters to confirm the diagnosis, to assess the severity and to monitor progression of AS. Aortic valve replacement (AVR) is indicated in symptomatic patients with severe AS, but in asymptomatic patients with severe AS there is an ongoing controversial discussion whether these patients should undergo AVR or should be treated conservatively. For patients with moderate AS, surgical treatment is generally not recommended, even though recent data suggest that the outcome of these patients is worse than commonly assumed.In several studies that included patients with valvular AS, an elevation of BNP and NT-proBNP serum concentrations related to disease severity has been reported (Figure 1). Consequently, in a longitudinal study it was found, that NT-proBNP concentrations decrease after successful surgical therapy but increase in conservatively treated patients with AS (Figure 2). These changes of NT-proBNP values over time were related to changes of the transvalvular pressure gradient (Figure 3). Furthermore, it has been demonstrated in clinical outcome studies that elevated NT-proBNP and BNP values, respectively, were associated with an unfavorable clinical course especially in patients who were treated conservatively (Figure 4).Thus, these results suggest that natriuretic peptides can be used as biomarkers for the diagnostic work-up of patients with AS and might be helpful to decide on the optimal timing of AVR (Table 1).

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Severity of Illness Index; Statistics, Nonparametric; Time Factors; Treatment Outcome

Recent studies have questioned the presumed low-risk status of patients with asymptomatic nonsevere aortic stenosis (AS). Whether annual N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements are useful for risk assessment is unknown.. To assess the association of annual NT-proBNP measurements with clinical outcomes in patients with nonsevere AS.. Analysis of annual NT-proBNP concentrations in the multicenter, double-blind Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) randomized clinical trial was performed. SEAS was conducted from January 6, 2003, to April 1, 2008. Blood samples were analyzed in 2016, and data analysis was performed from February 10 to October 10, 2021. SEAS included 1873 patients with asymptomatic AS not requiring statin therapy with transaortic maximal flow velocity from 2.5 to 4.0 m/s and preserved ejection fraction. This substudy included 1644 patients (87.8%) with available blood samples at baseline and year 1.. Increased age- and sex-adjusted NT-proBNP concentrations at year 1 and a 1.5-fold or greater relative NT-proBNP concentration change from baseline to year 1. Moderate AS was defined as baseline maximal flow velocity greater than or equal to 3.0 m/s.. Aortic valve events (AVEs), which are a composite of aortic valve replacement, cardiovascular death, or incident heart failure due to AS progression, were noted. Landmark analyses from year 1 examined the association of NT-proBNP concentrations with outcomes.. Among 1644 patients, 996 were men (60.6%); mean (SD) age was 67.5 (9.7) years. Adjusted NT-proBNP concentrations were within the reference range (normal) in 1228 of 1594 patients (77.0%) with NT-proBNP values available at baseline and in 1164 of 1644 patients (70.8%) at year 1. During the next 2 years of follow-up, the AVE rates per 100 patient-years for normal vs increased adjusted NT-proBNP levels at year 1 were 1.39 (95% CI, 0.86-2.23) vs 7.05 (95% CI, 4.60-10.81) for patients with mild AS (P < .01), and 10.38 (95% CI, 8.56-12.59) vs 26.20 (95% CI, 22.03-31.15) for those with moderate AS (P < .01). Corresponding all-cause mortality rates were 1.05 (95% CI, 0.61-1.81) vs 4.17 (95% CI, 2.42-7.19) for patients with mild AS (P < .01), and 1.60 (95% CI, 0.99-2.57) vs 4.78 (95% CI, 3.32-6.87) for those with moderate AS (P < .01). In multivariable Cox proportional hazards regression models, the combination of a 1-year increased adjusted NT-proBNP level and 1.5-fold or greater NT-proBNP level change from baseline was associated with the highest AVE rates in both patients with mild AS (hazard ratio, 8.12; 95% CI, 3.53-18.66; P < .001) and those with moderate AS (hazard ratio, 4.05; 95% CI, 2.84-5.77; P < .001).. The findings of this study suggest that normal NT-proBNP concentrations at 1-year follow-up are associated with low AVE and all-cause mortality rates in patients with asymptomatic nonsevere AS. Conversely, an increased 1-year NT-proBNP level combined with a 50% or greater increase from baseline may be associated with high AVE rates.. ClinicalTrials.gov Identifier: NCT00092677.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Female; Humans; Male; Natriuretic Peptide, Brain; Oceans and Seas; Peptide Fragments; Prognosis

Left ventricular diastolic dysfunction is common in patients with aortic valve stenosis (AS) and reportedly affects prognosis after surgical aortic valve replacement (SAVR). Here we investigated whether and how diastolic function (assessed following the most recent guidelines) was affected by SAVR, and whether preoperative diastolic function affected postoperative outcome. We also examined whether long-term mortality was associated with preoperative NT-proBNP and postoperative heart failure (PHF).. We performed a prospective observational study of 273 patients with AS who underwent AVR with or without concomitant coronary artery bypass surgery. Of these patients, 247 were eligible for assessment of left ventricular (LV) filling pressure. Preoperatively and at the 6-month postoperative follow-up, we measured N-terminal pro-B type natriuretic peptide (NT-proBNP) in serum and assessed diastolic function with Doppler echocardiography. PHF was diagnosed using prespecified criteria. Multivariable logistic regression was performed to explore variables associated with high LV filling pressure. Cox regression was performed to explore variables associated with mortality, accounting for timeto-event.. At the time of surgery, 22% (n = 54) of patients had diastolic dysfunction expressed as high LV filling pressure. Of these 54 patients, 27 (50%) showed postoperative diastolic function improvement. Among the 193 patients with preoperative low LV filling pressure, 24 (12%) showed postoperative diastolic function deterioration. Increased long-term mortality was associated with PHF and high preoperative NT-proBNP, but not with preoperative or postoperative diastolic dysfunction. Cox regression revealed the following independent risk factors for long-term mortality: diabetes, renal dysfunction, preoperative NT-proBNP>960 ng/L, age, and male gender.. Surgery for aortic stenosis improved diastolic function in patients with high LV filling pressure in 50% of the patients. Our results could not confirm the previously suggested role of diastolic dysfunction as a marker for poor long-term survival after SAVR. Our findings showed that both PHF and high preoperative NT-proBNP were associated with long-term mortality.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Heart Valve Prosthesis Implantation; Humans; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ventricular Function, Left

Topics: Aged; Anticholesteremic Agents; Aortic Valve Stenosis; Cause of Death; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hypernatremia; Hyponatremia; Incidence; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models

B-type natriuretic peptide (BNP) is a cardiac neurohormone that is secreted in response to ventricular volume expansion and pressure overload. There are conflicting data regarding the association between BNP levels and outcomes after transcatheter aortic valve replacement (TAVR). We therefore sought to assess the association between baseline BNP and adverse outcomes in patients with symptomatic, severe aortic stenosis (AS), and left ventricular ejection fraction (LVEF) ≥50%, undergoing TAVR in the PARTNER 2 Trial and Registry.. A total of 1782 patients were included in the analysis, and BNP was evaluated both as a continuous log-transformed value and by a priori categories: low (<50 pg/mL), normal (≥50 and <100 pg/mL), moderately elevated (≥100 and <400 pg/mL), or markedly elevated (≥400 pg/mL). Clinical outcomes from discharge to 2 years were compared between patients according to their baseline BNP level, using Kaplan-Meier event rates and multivariable Cox proportional hazards regression models. After adjustment, spline curves revealed a non-linear association between log-transformed BNP and all-cause and cardiovascular mortality in which both the lowest and highest values were associated with increased mortality. Two-year all-cause mortality rates for those with low (n = 86), normal (n = 202), moderately elevated (n = 885), and markedly elevated (n = 609) baseline BNP were 20.0%, 9.8%, 17.7%, and 26.1%, respectively. In adjusted models, compared to a normal baseline BNP, low [adjusted hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.3-5.0, P-value 0.005], moderately elevated (adjusted HR 1.6, 95% CI 1.0-2.6, P-value 0.06), and markedly elevated (adjusted HR 2.1, 95% CI 1.3-3.5, P-value 0.003) BNP were associated with increased all-cause mortality, driven by cardiovascular mortality.. In a large cohort of patients with severe symptomatic AS and preserved LVEF undergoing TAVR, all-cause and cardiovascular mortality rates at 2 years were higher in patients with low and markedly elevated BNP levels.. https://clinicaltrials.gov/ unique identifier #NCT01314313, #NCT02184442, #NCT03222128, and #NCT03222141.

Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Registries; Risk Factors; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left

Inflammation is involved in initiation and progression of aortic stenosis (AS). However, the role of the complement system, a crucial component of innate immunity in AS, is unclear. We hypothesized that circulating levels of complement factor B (FB), an important component of the alternative pathway, are upregulated and could predict outcome in patients with severe symptomatic AS. Therefore, plasma levels of FB, Bb, and terminal complement complex were analyzed in three cohorts of patients with severe symptomatic AS and mild-to-moderate or severe asymptomatic AS (population 1,

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; C-Reactive Protein; Complement Factor B; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Troponin T

This study was conducted to assess expression of Galectin-3 (Gal-3) in patients with different types of left ventricle (LV) hypertrophy geometry, and the relationship between Gal-3 expression and LV remodelling in patients with aortic valve stenosis (AS).. Galectin-3 expression was measured in the plasma and myocardia of AS patients who underwent an aortic valve replacement procedure.. The study enrolled 77 consecutive patients with severe AS. Fifty-five (71.43%) of the enrolled patients had concentric hypertrophy (CH group), and had the highest degree of fibrosis (27.10±5.25%; p<0.001) and expression of Gal-3 in both plasma (19.11±2.06 ng/mL) and myocardial tissue (3.01±0.79). There was a strong positive correlation between the levels of fibrosis and Gal-3 expression in both plasma (r=0.584, p<0.001) and myocardium (r=0.522, p<0.001). Relative wall thickness (RWT) was strongly correlated with Gal-3 expression in both myocardium (r=0.594, p<0.001) and plasma (r=0.323, p=0.005). Additionally, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with both fibrosis (r=0.313, p=0.036) and LV mass index (r=0.559, p<0.001).. Concentric hypertrophy geometry was the most common type of myocardium remodelling, and AS patients with CH geometry showed the highest levels of Gal-3 expression. Galectin-3 levels were positively correlated with fibrosis and RWT, both of which are crucial indicators of geometric remodelling. Galectin-3 and NT-proBNP levels may be valuable prognostic predictors in AS patients with myocardial remodelling.

Topics: Adult; Aortic Valve Stenosis; Blood Proteins; Female; Galectin 3; Galectins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Remodeling

: In experimental aortic stenosis (AS), blockade of the renin-angiotensin system attenuates AS-related left ventricular (LV) dysfunction and improves survival. We tested whether candesartan, an angiotensin II type 1 receptor blocker, favorably influences LV structure and function and improves exercise capacity in AS patients. Fifty-one patients with severe AS were randomized to receive candesartan (target dose 16 mg/d) or placebo. Eight patients discontinued treatment and the remaining 43 patients underwent echocardiography, walking test, and measurement of plasma N-terminal B-type natriuretic peptide (Nt-proBNP) before and after an average of 5-month treatment. No statistically significant changes in LV diameters, mass, or function were seen. The median 6-minute walking distance decreased from 390 to 368 m with candesartan (P = 0.003) and from 380 to 370 m with placebo (P = 0.523), reflecting natural progression of AS. Concomitantly, median Nt-proBNP increased from 319 to 414 ng/L with candesartan (P = 0.170) and from 413 to 561 ng/L with placebo (P = 0.035). No change with candesartan was statistically significantly different from the corresponding change with placebo. In conclusion, candesartan was well tolerated but had no favorable effects on the LV or effort tolerance. The benefits found in experimental AS of blocking the renin-angiotensin system could not be reproduced in patients with severe AS.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Aortic Valve Stenosis; Benzimidazoles; Biomarkers; Biphenyl Compounds; Disease Progression; Exercise Tolerance; Female; Finland; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Recovery of Function; Renin-Angiotensin System; Severity of Illness Index; Tetrazoles; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

B-type natriuretic peptide (BNP) levels have shown a correlation with outcomes in studies of aortic valve surgery. Results from multicenter trials of BNP in transcatheter aortic valve surgery (TAVR) are lacking. The aim of this study was to investigate the prognostic role of serial measurement of BNP in transfemoral TAVR. A total of 1,097 patients who underwent TAVR via transfemoral access were analyzed by tertile of baseline BNP. Of those, 933 with BNP levels at 30 days were divided into 2 groups on the basis of increases (334 patients) or decreases or no change (599 patients) in BNP compared with baseline. Patients in the low-tertile BNP group had a lower rate of death at 1 year than those in the higher tertile group (15.0% vs 23.0%, p<0.01) which was not significant in multivariate analysis. Over 1 year, BNP decreased from 1,258.13±2,988.33 to 594.37±1,087.30 (p<0.01) in the entire group. Patients in the BNP-rise group had higher rates of death at 1 year (20.3% vs 11.4%, p<0.01) and an overall increase in moderate or severe aortic regurgitation over 1 year (p<0.01). Multivariate predictors of 1-year mortality were moderate or severe aortic regurgitation (hazard ratio 2.04, 95% confidence interval 1.36 to 3.05, p<0.01), increase in BNP at 30 days (hazard ratio 1.82, 95% confidence interval 1.26 to 2.62, p<0.01) and Society of Thoracic Surgeons score (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p=0.03). In conclusion, increase in BNP at 30 days from baseline and moderate or severe aortic regurgitation at 30 days in patients who undergo transfemoral TAVR are independently associated with 1-year mortality. Increase in BNP at 30 days should prompt evaluation for causes of elevated wall stress, including aortic regurgitation.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cohort Studies; Female; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Transcatheter Aortic Valve Replacement; Treatment Outcome

High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.. Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity.. In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.

Topics: Aged; Aortic Valve Stenosis; Biological Assay; Biomarkers; Contrast Media; Early Diagnosis; Female; Fibrosis; Follow-Up Studies; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Magnetic Resonance Angiography; Male; Myocardium; Natriuretic Peptide, Brain; Organometallic Compounds; Prognosis; Stroke Volume; Tomography, X-Ray Computed; Troponin I

Study elucidates and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis.. Twenty-two patients were prospectively randomized in two groups regarding the anesthetic regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac injury and brain natriuretic peptide (BNP) were measured preoperatively and postoperatively. In tissue samples, taken from the interventricular septum, key mitochondrial molecules were determined by Western blot, real time PCR, as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis.. The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content was higher in propofol than sevoflurane receiving patients. Propofol group also showed higher protein level of connexin 43 (Cx43) than sevoflurane group. Besides, immunogold analysis showed its mitochondrial localization. The mRNA level of mtDNA and uncoupling protein (UCP2) were higher in propofol than sevoflurane patients, as well. On the other hand, there were no significant differences between groups in hemodynamic assessment, intensive care unit length of stay, troponin I and BNP level.. Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms. It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase, while the effects of propofol occur through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2.

Topics: Aged; Anesthetics; Aortic Valve; Aortic Valve Stenosis; ATP Synthetase Complexes; Cardiopulmonary Bypass; Connexin 43; Cytochromes c; DNA, Mitochondrial; Female; Hemodynamics; Humans; Ion Channels; Male; Methyl Ethers; Middle Aged; Mitochondria; Mitochondrial Proteins; Natriuretic Peptide, Brain; Propofol; Prospective Studies; Sevoflurane; Troponin I; Uncoupling Protein 2

The study aims were to test the effect of rosuvastatin on the progression of left ventricular (LV) diastolic function in patients with aortic stenosis (AS), and to evaluate the use of beta-natriuretic-peptide (BNP) as a marker of diastolic dysfunction in this condition.. Sixty-one hypercholesterolemic, consecutive new referrals with moderate AS were administered rosuvastatin (Crestor) 20 mg/day for 18 months, while a further 60 subjects with normal cholesterol levels remained untreated. The LV diastolic function was determined using conventional Doppler echocardiography, tissue Doppler imaging (TDI); BNP plasma levels were monitored when subjects entered the study and then assessed prospectively at six-month intervals until the study end.. After an 18-month (mean 73 +/- 24 weeks) period of treatment with rosuvastatin (Tx group), patients showed a significantly better diastolic function than untreated subjects (uTx group), as indicated by an isovolumic relaxation time (IVRT) (Tx 102.0 +/- 42.8 versus 97.2 +/- 19.1; p < 0.001; uTx 99.7 +/- 21.7 versus 95.2 +/- 21.8 ms; p = 0.032), E/A ratio (Tx 1.0 +/- 0.6 versus 0.9 +/- 0.3, p = 0.52; uTx 1.2 +/- 0.40 versus 0.9 +/- 0.30 versus, p = 0.006), and E/E' ratio (Tx 11.4 +/- 1.5 versus 11.4 +/- 1.8, p = 0.19; uTx 15.4 +/- 1.2 versus 12.3 +/- 1.5, p < 0.001). Similarly, at study end, plasma levels of BNP were significantly lower in the Tx group than in the uTx group [median (1st-3rd quartiles): 37.0 pg/ml (20.1-65.2 pg/ml) versus 57.1 pg/ml (46.9-98.2 pg/ml); p = 0.017].. The results of this prospective follow up study of asymptomatic patients showed that rosuvastatin treatment delays the progression of diastolic dysfunction in moderate AS when assessed using hemodynamic echocardiographic parameters or by the release of plasma physiological markers. Hence, the benefits of statin treatment in AS, which are known to affect the valve endothelium, also extend to changes affecting myocardial function itself.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Calcinosis; Diastole; Disease Progression; Echocardiography; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure, Diastolic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Treatment Outcome; Ventricular Dysfunction, Left

One of the hemodynamic consequences of aortic valve stenosis is pressure overload leading to left atrial dilatation. Left atrial size is a known risk factor providing prognostic information in several cardiac conditions. It is not known if this is also the case in patients with aortic valve stenosis after aortic valve replacement.. A total of 119 patients with severe aortic valve stenosis scheduled for aortic valve replacement were evaluated preoperatively and divided into 2 groups according to left atrial volume index (≥40 mL/m(2)). Echocardiography was repeated 12 months after surgery. Patients were followed up for 24 months. The primary end point was the composite end point overall mortality and hospitalization due to congestive heart failure.. Preoperative left atrial dilation was associated with left ventricular hypertrophy and increased filling pressure. Preoperative left atrial volume index was associated with persistent abnormalities in left ventricular filling pressure and left ventricular mass index at 1 year after surgery. Event-free survival in patients with left atrial volume index of 40 mL/m(2) or more at 1 year was 71% compared with 88% in patients with left atrial volume index less than 40 mL/m(2) (P = .002). Patients with preoperative increased E/e' ratio and left ventricular hypertrophy were at increased risk. In Cox regression analysis after correcting for standard risk factors, left atrial volume index was found to be the only significant predictor of the composite end point. In a forward conditional multivariable model, left atrial volume index 40 mL/m(2) or greater (hazard ratio, 4.2 [1.6-10.7]; P = .003) remained an independent predictor, whereas E/e' was borderline significant (P = .06).. In patients with symptomatic severe aortic valve stenosis undergoing aortic valve replacement, left atrial volume provides important prognostic information beyond standard risk factors.

Topics: Aged; Aortic Valve Stenosis; Atrial Function, Left; Dilatation, Pathologic; Female; Heart Atria; Heart Failure; Heart Valve Prosthesis Implantation; Hospitalization; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Risk Factors; Treatment Outcome; Ultrasonography; Ventricular Remodeling

Recent trials have failed to show that statin therapy halts the progression of calcific aortic stenosis (AS). We hypothesized that statin therapy in younger patients with congenital AS would be more beneficial, because the valve is less calcified. In the present double-blind, placebo-controlled trial, 63 patients with congenital AS (age 18 to 45 years) were randomly assigned to receive either 10 mg of rosuvastatin daily (n = 30) or matched placebo (n = 33). The primary end point was the progression of peak aortic valve velocity. The secondary end points were temporal changes in the left ventricular mass, ascending aortic diameter, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The median follow-up was 2.4 years (interquartile range 1.9 to 3.0). The mean increase in peak velocity was 0.05 ± 0.21 m/s annually in the rosuvastatin group and 0.09 ± 0.24 m/s annually in the placebo group (p = 0.435). The annualized change in the ascending aorta diameter (0.4 ± 1.7 mm with rosuvastatin vs 0.5 ± 1.6 mm with placebo; p = 0.826) and left ventricular mass (1.1 ± 15.8 g with rosuvastatin vs -3.7 ± 30.9 g with placebo; p = 0.476) were not significantly different between the 2 groups. Within the statin group, the NT-proBNP level was 50 pg/ml (range 19 to 98) at baseline and 21 pg/ml (interquartile range 12 to 65) at follow-up (p = 0.638). NT-proBNP increased from 40 pg/ml (interquartile range 20 to 92) to 56 pg/ml (range 26 to 130) within the placebo group (p = 0.008). In conclusion, lipid-lowering therapy with rosuvastatin 10 mg did not reduce the progression of congenital AS in asymptomatic young adult patients. Interestingly, statins halted the increase in NT-proBNP, suggesting a potential positive effect of statins on cardiac function in young patients with congenital AS.

Topics: Adolescent; Adult; Aortic Valve; Aortic Valve Stenosis; Belgium; Blood Flow Velocity; Calcinosis; Disease Progression; Double-Blind Method; Echocardiography, Doppler; Female; Fluorobenzenes; Follow-Up Studies; Heart Valve Prosthesis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Young Adult

The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 +/- 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal-pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Atorvastatin; C-Reactive Protein; Calcinosis; Cholesterol; Disease Progression; Female; Heart Valve Prosthesis; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Pyrroles; Risk Factors; Tomography, X-Ray Computed

The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome.. BNP was measured in 69 patients with low-flow AS (indexed effective orifice area < 0.6 cm2/m2, mean gradient < or = 40 mm Hg, left ventricular ejection fraction < or = 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area < or = 1.0 cm2 or > 1.0 cm2). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient r(s)=-0.59, P<0.0001) and at peak stress (r(s)=-0.51, P<0.0001), effective orifice area at rest (r(s)=-0.50, P<0.0001) and at peak stress (r(s)=-0.46, P=0.0002), and mean transvalvular flow (r(s)=-0.31, P=0.01). BNP was directly related to valvular resistance (r(s)=0.42, P=0.0006) and wall motion score index (r(s)=0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP > or = 550 pg/mL was only 47+/-9% versus 97+/-3% with BNP < 550 (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP > or = 550 pg/mL (53+/-13% versus 92+/-7%).. BNP is significantly higher in truly severe than pseudosevere low-gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Pressure; Cardiac Output; Cardiovascular Abnormalities; Child; Heart Rate; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Ventricular Function, Left

The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in relation to clinical and echocardiographic variables and N-terminal pro-B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction > 50%.. LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk.. Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value.. In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Atrial Fibrillation; Heart Atria; Humans; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Stroke Volume; Ventricular Function, Left

Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR.. We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (<60% or ≥60% predicted) and NT-Pro-BNP (<1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years.. Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90-96)] and 5 [45.3% (95% CI: 35.4-58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69-83)] and 5 years [13.1% (95% CI: 7-25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6-3.2, P < 0.001) with 25.7% of patients in New York Heart Association class III-IV. Patients in groups B and C had intermediate outcomes.. The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Forced Expiratory Volume; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Transcatheter Aortic Valve Replacement

Patients undergoing transcatheter aortic valve replacement surgery (TAVR) are typically older adults with multiple chronic diseases and therefore have a high surgical risk. The N-terminal of brain natriuretic peptide (BNP) and pro-BNP, referred to as NT-pro-BNP, is an easily measurable biomarker of heart failure. Studies on correlation between higher NT-pro-BNP levels and adverse prognoses after TAVR have yielded inconsistent results. Here, we investigated whether preoperative NT-pro-BNP levels are correlated with outcomes among older adults undergoing TAVR.. This retrospective study included older adults with severe aortic stenosis (AS) who received TAVR from a medical center between January 2013 and June 2017. The patients' demographics, preoperative laboratory data, postoperative complications, and 1-year mortality were recorded. They were divided into two groups based on their preoperative NT-pro-BNP levels. The post-TAVR outcomes in the two groups were analyzed using a multivariate logistic regression analysis of the binary results.. Of the 132 patients included (mean age: 81.5 ± 8.1 years; 47% men), 96 (72.7%) had preoperative NT-pro-BNP levels ≤ 4853 ng/L, and 36 (27.3%) had preoperative NT-pro-BNP levels > 4853 ng/L. The postoperative outcomes were significantly better in the NT-pro-BNP≤4853 group than in the NT-pro-BNP>4853 group: postoperative extracorporeal membrane oxygenation fittings (4.2% vs 16.7%, p = 0.025), number of days in hospital (17.5 ± 21.0 vs 27 ± 17.0, p = 0.009), in-hospital mortality (4.2% vs 16.7%, p = 0.025), and 1-year mortality (11.5% vs 38.9%, p = 0.001); the significant differences persisted after controlling for other variables.. For older patients undergoing TAVR with NT-pro-BNP levels > 4853 ng/L, their postoperative outcomes and 1-year mortality were correlated. Thus, NT-pro-BNP is useful for the risk assessment of patients undergoing TAVR and should be regarded as a biomarker in future risk assessments.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Transcatheter Aortic Valve Replacement

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity.

Topics: Aortic Valve; Aortic Valve Stenosis; Fibroblasts; Gallium Radioisotopes; Humans; Hypertension; Molecular Imaging; Natriuretic Peptide, Brain; Pilot Projects; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left

We aimed to assess the incremental prognostic value of N-terminal-pro-B-type natriuretic peptide (Nt-proBNP) for risk stratification in mixed aortic valve disease (MAVD) patients.. We included 556 (73±12 years, 37% women) consecutive patients with at least a moderate aortic stenosis (AS) or aortic regurgitation (AR) lesion with a concomitant AS or AR of any severity in whom Nt-proBNP was measured and expressed as its ratio (measured Nt-proBNP divided by the upper limit of normal Nt-proBNP for age and sex). The primary endpoint was all-cause mortality.. Baseline median Nt-proBNP ratio was 3.8 (IQR: 1.5-11.3), and the median follow-up was 5.6 years (4.8-6.1). Early aortic valve replacement (AVR) was performed within 3 months in 423 (76%) patients, while 133 (24%) remained initially under medical treatment. In comprehensive multivariable analyses, Nt-proBNP ratio was significantly associated with excess mortality (continuous variable: HR (95% CI): 1.24 (1.04 to 1.47), p=0.02; Nt-proBNP ratio ≥3: 2.41 (1.33 to 4.39), p=0.004). The independent prognostic value was also observed in patients with severe or non-severe AS/AR, and those treated by early-AVR (all p<0.04). Nt-proBNP ratio as continuous and dichotomic (≥3) variables showed incremental prognostic value (all net reclassification index >0.42, all p≤0.008). After early-AVR, Nt-proBNP ratio ≥3 was associated with higher 30-day mortality (9 (4%) vs 1 (0.5%), p=0.02).. In this series of MAVD patients, Nt-proBNP ratio was a powerful predictor of early and long-term mortality, even in patients with both non-severe AS/AR. Moreover, early-AVR may be an option for patients with Nt-proBNP ratio ≥3. Further randomised studies are needed to validate this last point.

Topics: Aged; Aged, 80 and over; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Limited data on the prognostic value of periprocedural changes of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) after transcatheter aortic valve replacement (TAVR).. Data of plasma NT-proBNP were retrospectively collected in 357 patients before TAVR procedure and at discharge from January 1, 2018 to December 31, 2021 in our single center. Patients were grouped as responders and non-responders according to the NT-proBNP ratio (postprocedural NT-proBNP at discharge/ preprocedural NT-proBNP). Responders were defined as NT-proBNP ratio < 1 and non-responders were defined as NT-proBNP ratio ≥ 1. Outcomes were defined according to the Valve Academy Research Consortium (VARC)-3 criteria.. A total of 234 patients (65.5%) and 123 patients (34.5%) were grouped as the responders and the non-responders, respectively. Responders and non-responders were significantly different in both median preprocedural (2103.5 vs. 421.0 pg/ml, p < 0.001) and postprocedural (707.6 vs. 1009.0, p < 0.001) NT-proBNP levels. Patients in the non-responder group were more inclined to have comorbidities of hypertension (73.2% vs. 51.7%, p < 0.001), hyperlipidaemia (46.3% vs. 34.6%, p = 0.031), peripheral vascular disease (20.3% vs. 8.5%, p = 0.001) and pure aortic insufficiency (15.4% vs. 4.3%, p < 0.001). In the contrast, patients in the responder group had higher prevalence of maximum transvalvular velocity (4.6 vs. 4.2 m/s, p < 0.001), reduced left ventricular ejection fraction (58.0% vs. 63.0%, p < 0.001), heart failure (9.4% vs. 2.4%, p = 0.014), mitral regurgitation ≥ moderate (13.7% vs. 4.9%, p = 0.010), tricuspid regurgitation ≥ moderate (12.0% vs. 2.4%, p = 0.002), and pulmonary hypertension (32.9% vs. 13.0%, p < 0.001). Patients in the non-responder group were moderately longer than the responder group in total hospitalization length (14 vs. 12 days, p < 0.001). The non-responder group were significantly associated with cumulative all-cause mortality (p = 0.009) and cardiac mortality (p < 0.001) during the follow-up period.. Periprocedural changes of NT-proBNP is clinically useful for the risk stratification of survival in patients after TAVR.

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Stroke Volume; Transcatheter Aortic Valve Replacement; Ventricular Function, Left

The indications or timing of aortic valve replacement for symptomatic aortic stenosis (AS) are based on a patient's life expectancy and symptoms. However, clinical decision-making may be difficult because symptoms are subjective and cannot be quantitatively assessed and confirmed. This study aimed to evaluate the association between heart failure (HF)-related symptoms and cardiac hemodynamic left ventricular deformations in patients with severe AS using transthoracic echocardiographic assessments of left ventricular global longitudinal strain (LV-GLS). The medical records of patients hospitalized for AS between February 2017 and September 2019 were retrospectively screened. Independent cardiologists analyzed the transthoracic echocardiographic images of a digital echocardiography database. The cohort comprised 177 hospitalized patients with severe AS and no history of HF. The subgroup with HF-related symptoms included 87 patients, whereas that without HF-related symptoms included 90 patients. In 145 patients without atrial fibrillation, the left atrial volume index (LAVI) and LV-GLS were significantly associated with HF-related symptoms (odds ratio 1.033, 95% confidence interval 1.008 to 1.059, p = 0.011 and odds ratio 1.224, 95% confidence interval 1.118 to 1.340, p <0.0001, respectively). Moreover, the combination of brain natriuretic peptide level, LAVI, and LV-GLS showed better diagnostic accuracy than the combination of brain natriuretic peptide level and LAVI (p = 0.005). However, there were no such tendencies in 32 patients with atrial fibrillation. The HF-related symptoms in patients with severe AS were strongly linked to LV-GLS. LV-GLS showed incremental value for confirming HF-related symptoms.

Topics: Aortic Valve Stenosis; Atrial Fibrillation; Global Longitudinal Strain; Heart Failure; Humans; Natriuretic Peptide, Brain; Retrospective Studies; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Rapid progression of aortic stenosis (AS) is associated with poor outcomes, and the impact of B-type natriuretic peptide (BNP) on AS progression remains unknown.. The purpose of the present study was to investigate the association between BNP level and the AS progression rate.. From January 2016 to June 2021, 200 AS patients with progression who had at least two transthoracic echocardiograms with a maximum interval of 180 days were retrospectively analyzed. Rapid progression of AS was defined as the annual increase of aortic jet velocity (Vmax) ≥0.3 m/s/year. For analyses, both the log-transformed BNP and the BNP ratio were used. The linear regression and binary logistic regression analyses were used to determine the association between BNP and the AS progression.. At a median echocardiographic follow-up of 595 days, the annual median (interquartile) progression of Vmax was 0.26 (0.09-0.58) m/s/year. Patients with rapid progression had higher age, log BNP, and higher percentage of diabetes and male gender. Higher tertiles of log BNP and BNP ratio had more rapid increase in Vmax (. Higher BNP was independently associated with the rapid progression of AS.

Topics: Aortic Valve Stenosis; Biomarkers; Disease Progression; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Retrospective Studies

We investigated the prognostic significance of selected known and novel circulating biomarkers in aortic stenosis (AS).. N-terminal pro-BNP (NT-proBNP), high-sensitivity troponin-T (hsTnT), growth differentiation factor-15 (GDF-15), suppression of tumorigenicity-2 (ST2), mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) were measured in patients with moderate to severe AS, New York Heart Association (NYHA) class I-II and left ventricular ejection fraction ≥50%, recruited consecutively across five centres from 2011 to 2018. Their ability to predict both primary (all-cause mortality, heart failure hospitalisation or progression to NYHA class III-IV) and secondary (additionally incorporating syncope and acute coronary syndrome) outcomes was determined by competing risk analyses.. Among 173 patients with AS (age 69±11 years, 55% male, peak transaortic velocity (Vmax) 4.0±0.8 m/s), the primary and secondary outcomes occurred in 59 (34%) and 66 (38%), respectively. With aortic valve replacement as a competing risk, the primary outcome was determined consistently by the comorbidity index and each selected biomarker except ST2 (p<0.05), independent of NYHA class, Vmax, LV-global longitudinal strain and serum creatinine. MR-proADM had the highest discriminative value for both primary (subdistribution HR (SHR) 11.3, 95% CI 3.9 to 32.7) and secondary outcomes (SHR 12.6, 95% CI 4.7 to 33.5). Prognostic assessment of dual-biomarker combinations identified MR-proADM plus either hsTnT or NT-proBNP as the best predictive model for both clinical outcomes. Paired biomarker models were not superior to those including MR-proADM as the sole circulating biomarker.. MR-proADM most powerfully portended worse prognosis and should be further assessed as possibly the biomarker of choice for risk stratification in AS.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Aortic Valve Stenosis; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Stroke Volume; Ventricular Function, Left

There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively.. The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Topics: Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Female; Heart Valve Prosthesis Implantation; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Registries; Risk Factors; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome

Topics: Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Among patients with chronic kidney disease (CKD), aortic stenosis (AS) is associated with a significantly higher rate of mortality. We aimed to evaluate whether diffuse myocardial fibrosis, determined using native T1 mapping, has prognostic utility in predicting major adverse cardiovascular events (MACEs), including all-cause mortality or heart failure hospitalization, in patients with CKD and severe AS who are evaluated for transcatheter aortic valve implantation. Cardiac magnetic resonance with T1 mapping using the modified Look-Locker inversion recovery technique was performed in 117 consecutive patients with severe AS and CKD (stage ≥3). Patients were followed up to determine the occurrence of MACE. The mean age of the 117 patients in the cohort was 82 ± 8 years. Native T1 was 1,055 ms (25th- to 75th percentiles 1,031 to 1,078 ms), which is higher than previously reported in healthy controls. Patients with higher T1 times were more likely to have higher N-terminal pro-B-type natriuretic peptide levels (4,122 [IQR 1,578 to 7,980] pg/ml vs 1,678 [IQR 493 to 2,851] pg/ml, p = 0.005) and a history of heart failure (33% vs 9%, p = 0.034). After median follow-up of 3.4 years, MACE occurred in 71 patients (61%). The Society of Thoracic Surgeons predicted risk of mortality score (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.02 to 1.12, p = 0.006), native T1 >1,024 ms (HR 2.10, 95% CI 1.09 to 4.06, p = 0.028), and New York Heart Association class (HR 1.56, 95% 1.09 to 2.34, p = 0.016) were independent predictors of MACE. Longer native T1 was associated with MACE occurrence in patients with CKD and severe AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Fibrosis; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Humans; Natriuretic Peptide, Brain; Prospective Studies; Retrospective Studies; Stroke Volume; Transcatheter Aortic Valve Replacement; Troponin; Ventricular Function, Left

Presepsin is a rather novel blood parameter that is most commonly used for the detection of severe infections. However, in patients without infections who are undergoing elective surgery, elevated baseline presepsin levels were also found to be associated with worse survival. In this study, researchers wanted to know whether increased presepsin levels can also predict worse survival in patients who are planned for transcatheter aortic valve implantation. To do so, they looked at the 1-year death rate of these patients and distinguished between low and high presepsin levels determined before the procedure. Patients with elevated presepsin levels before the procedure had a worse outcome after 1 year compared with those with low presepsin levels. Measurement of presepsin before the transcatheter aortic valve implantation procedure could help identify patients who are at a higher long-term risk, and accordingly a closer monitoring of these patients during the follow-up period might be warranted.

Topics: Aortic Valve Stenosis; Biomarkers; Humans; Lipopolysaccharide Receptors; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome

The 2016 guidelines of the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) for evaluation of left ventricular (LV) diastolic dysfunction by Doppler flow and tissue Doppler- echocardiography do not adjust assessment of high filling pressures for patients with aortic stenosis (AS). However, most of the studies on this patient group indicate age independent specific diastolic features in AS. The aim of this study is to identify disease-specific range and distribution of diastolic functional parameters and their ability to identify high N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels as a marker for high filling pressures.. In this study, 169 patients who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Resting echocardiography was performed including Doppler of the mitral inflow, pulmonary venous flow, tricuspid regurgitant flow and tissue Doppler in the mitral ring and indexed volume-estimates of the left atrium (LAVI). Echocardiography, and NT-proBNP levels were assessed before TAVR/SAVR and at two postoperative visits at 6 and 12 months.. Diastolic echocardiographic parameters in AS indicate persistent impaired relaxation and NT-proBNP indicate elevated filling pressures in most of the patients, improving only modestly 6-12 months after TAVR and SAVR. Applying the 2016 ASE/EACVI recommendations for detection of elevated filling pressures to patients with AS, elevated NT pro-BNP levels could not be reliably detected. However, adjusting thresholds of the echocardiographic parameters increased specificities to useful diagnostic levels.. The study was prospectively approved by the regional ethical committee, REK North with the registration number: REK 2010/397-10 .

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Diastole; Echocardiography; Echocardiography, Doppler; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS.. We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure-related hospital admission (DHFA). We also utilized machine-learning methods (a tree-based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow-up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)-α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)-23 (HR 1.22, P < 0.0001), N-terminal pro B-type natriuretic peptide (NT-proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase-7 (HR 1.24, P = 0.0002), syndecan-1 (HR 1.27, P = 0.0002), suppression of tumorigenicity-2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)-8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)-3 (HR 1.17, P = 0.001), neutrophil gelatinase-associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF-23 (HR 1.36, P < 0.0001), TNF-α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin-2 (HR 1.26, P < 0.0001), syndecan-1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL-8 (HR 1.18, P = 0.0009), PTX-3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT-proBNP (HR 1.63, P < 0.0001). Machine-learning multimarker models were strongly associated with adverse outcomes (mean 1-year probability of death of 0%, 2%, and 60%; mean 1-year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL-6 (a biomarker of inflammation) and FGF-23 (a biomarker of calcification) emerged as the biomarkers of highest importance.. Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis.

Topics: Aortic Valve Stenosis; Biomarkers; Calcinosis; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Transcatheter aortic valve implantation (TAVI) is a valuable treatment option for patients with reduced left ventricular ejection fraction (LVEF) and low-flow/low-gradient (LF/LG) aortic stenosis (AS). According to current literature, the presence of severe AS is unlikely in case of severely reduced LVEF and mean pressure gradient (meanPG) below 30 mmHg. However, a considerable number of patients presenting with typical clinical symptoms of severe AS, show gradients below 30 mmHg. We hypothesized, that these patients undergoing TAVI do have a measurable clinical benefit and an improved LVEF.. In this single center retrospective cohort study, data from 1199 patients undergoing TAVI between 2013 and 2017 was analyzed. A 6-month follow-up was performed to assess changes in NT-proBNP, NYHA-class, and LVEF.. Based on our findings TAVI represents a valuable treatment option even in patients with LF/LG AS and PGmean below 30mmHg.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Regional Blood Flow; Retrospective Studies; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Aortic Valve Stenosis; Asymptomatic Diseases; Biomarkers; Clinical Decision-Making; Echocardiography; Exercise Test; Heart Valve Prosthesis; Heart Valves; Heart Ventricles; Humans; Natriuretic Peptide, Brain; Risk Assessment; Severity of Illness Index; Stroke Volume; Tomography, X-Ray Computed; Troponin

Topics: Aged, 80 and over; Anti-Bacterial Agents; Aortic Valve Stenosis; Ceftriaxone; Computed Tomography Angiography; Embolectomy; Embolism; Endocarditis; Fatal Outcome; Gentamicins; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Streptococcus salivarius; Thrombosis; Transcatheter Aortic Valve Replacement; Ultrasonography, Doppler

Brain or B-type natriuretic peptide (BNP) is an objective marker to diagnose the presence of heart failure (HF) and assess its severity. However, the determinants of serum BNP level in elderly patients with severe aortic valve stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) have not been well investigated.. We prospectively studied 106 AS patients who underwent TAVI. Cardiac catheterization, transesophageal echocardiography, and blood collection for plasma BNP level measurements were performed simultaneously just before the TAVI procedures.. Ninety-nine patients (83.9±5.0 years, 33% male) were studied. The natural logarithm of BNP (lnBNP) level was 5.4±0.9 pg/mL. Significant correlations with lnBNP level were observed in: 1) the history of syncope, prior HF medication, and New York Heart Association class III or IV (R=0.255, p=0.011) (R=0.210, p=0.037) (R=0.402, p<0.001), 2) albumin and hemoglobin level (R=-0.289, p=0.004) (R=0.263, p=0.009), 3) Left ventricular (LV) ejection fraction and global longitudinal strain (LVGLS) (R=-0.338, p<0.001) (R=0.447, p<0.001), 4) LV end-diastolic volume index (EDVI), LV mass index, and left atrial volume index (R=0.280, p=0.005) (R=0.366, p<0.001) (R=0.337, p<0.001), 5) the catheter-measured pressure gradient across the aortic valve (AVPG) (R=0.365, p<0.001). Note that LV wall stress was not significantly correlated with lnBNP level. LVGLS, AVPG, hemoglobin level, and LVEDVI were independently correlated with ln BNP level (R=0.652, LVGLS; β=0.395, p<0.006, AVPG; β=0.291, p=0.001, hemoglobin level; β=-0.216, p=0.011, and LVEDVI; β=0.203, p=0.016, respectively).. In severe AS patients candidate for TAVI, multiple factors, including the severities of AS and HF conditions and subclinical LV dysfunction determined by LVGLS affects plasma BNP level.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Cardiac Catheterization; Female; Humans; Male; Natriuretic Peptide, Brain; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left

ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS).. Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valve implantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software.. Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF < 50%) ST2 concentrations were significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations.. Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment.

Topics: Aortic Valve Stenosis; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Retrospective Studies; Stroke Volume; Transcatheter Aortic Valve Replacement; Ventricular Dysfunction, Left

There is conflicting data as to whether diastolic dysfunction (DD) affects the prognosis of patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).. Consecutive patients undergoing TAVR underwent assessment of DD with preoperative echocardiography and NT-pro BNP. Long-term survival was ascertained every 6 months by clinic visits or phone. DD was graded according to the new American Society of Echocardiography recommendations. Health status was assessed at baseline and 30 days post-procedure using the KCCQ-12 questionnaire. Long-term survival was displayed using Kaplan-Meier curves according to NT-pro BNP levels and DD grades.. We included 222 patients, mean age 78 (±8) years, median STS score 4 (interquartile range = 3-7), median follow-up time 385 days (IQR = 180-640). DD was absent in 25, Grade I in 13, Grade II in 74, Grade III in 24, and indeterminate in 86 patients. Advanced (Grades II-III) DD was associated with higher pre-procedural NT-pro BNP levels (p < .001), worse quality of life (p < .001) but similar surgical risk (p = .43). Advanced and indeterminate DD were associated with increased long-term mortality (25-28% vs. 5%, p = .02) and elevated NT-pro BNP levels (26.4% vs. 9.8%, p = .05). Improvements in quality of life measures were seen in all DD groups (median change in KCCQ score no or Grade I DD:14 [3-21] vs. Grades II-III DD: 15 [16-26; p = .37]).. Preoperative NT-pro BNP levels and echocardiographic indices of indeterminate or advanced DD are associated with increased long-term mortality after TAVR but similar improvements in quality of life.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Diastole; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Quality of Life; Recovery of Function; Risk Assessment; Risk Factors; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Higher B-type natriuretic peptide (BNP) levels at discharge predict higher cardiovascular events in transcatheter aortic valve implantation (TAVI) patients. However, it is not known whether the reduction in BNP levels effectively predicts prognosis. The purpose was to examine the predictive power of percentage changes in BNP levels for all-cause death and hospitalization of heart failure (HF) after TAVI in severe aortic stenosis (AS) patients. We analyzed 70 severe AS patients treated with TAVI who had a record of BNP > 200 pg/mL. Receiver operating characteristics (ROC) curves analysis for all-cause death and hospitalization for HF after TAVI revealed the cut-off percentage change in BNP, and we divided the study population into the "responder group" and the "non-responder group". The cut-off level for the percentage change in BNP evaluated by ROC analysis was a 40% decrease in BNP (AUC = 0.733, p < 0.001). There were 48 patients (68.6%) in the responder group and 22 patients (31.4%) in the non-responder group. Kaplan-Meier estimates showed that the responder group had lower all-cause death and hospitalization for HF than the non-responder group by a log rank test (all-cause mortality; p = 0.006, hospitalization rate for HF; p < 0.001). The predictor of the non-responder group using multivariate logistic regression analysis was AF (OR 4.2, 95% CI 1.15-16.2, p = 0.03). A reduction of BNP was associated with improved prognosis after TAVI.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Atrial Fibrillation; Biomarkers; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Retrospective Studies; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome

There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with aortic stenosis could influence the choice/timing of treatment in these patients.. Exercise testing was performed on semi-supine ergobicycle. Cardiopulmonary analysis during exercise testing, echocardiography, and laboratory analysis at rest was done. Standard clinical/electrocardiography criteria were assessed for symptoms/signs of ischemia during/after exercise testing. In patients with normal exercise testing coronary angiography was performed using standard femoral/radial percutaneous approach. Coronary stenosis was considered significant if >70% of vessel diameter or 50%-70% with fractional flow reserve ≤0.8.. Total of 96 patients with normal exercise testing were included (67.6 years, 50.6% males). No patient had any complication or adverse event. The Pmean was 52.7 mmHg, mean indexed aortic valve area was 0.36 cm/m and left ventricular ejection fraction, 69.5%. 19/96 patients (19.8%) had significant coronary artery disease on coronary angiography. Multivariate logistic regression analysis revealed brain natriuretic peptide and blood glucose as independent predictors of silent coronary artery disease. Brain natriuretic peptide value of 118 pg/ml had sensitivity/specificity of 63%/73% for predicting coronary artery disease (area under the curve 0.727, P = 0.006).. Our results are the first to show that in patients with severe aortic stenosis, normal left ventricular ejection fraction,, and normal exercise testing, significant coronary artery disease is present in as many as 1/5 patients. In such patients, further prospective studies are warranted to address the diagnostic value of brain natriuretic peptide in detecting silent coronary artery disease.

Topics: Aged; Aortic Valve Stenosis; Asymptomatic Diseases; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Exercise Test; Female; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Sensitivity and Specificity; Severity of Illness Index

Biomarkers may significantly improve risk stratification algorithms for patients undergoing transcatheter aortic valve implantation (TAVI). While N-terminal pro-B-type natriuretic peptide (NT-proBNP) is established as a biomarker in the context of heart failure, its prognostic implications in patients with normal left ventricular ejection fraction (LVEF) undergoing TAVI are unclear.. A total of 504 TAVI patients with normal LVEF were analyzed. Based on preprocedural NT-proBNP levels, patients were stratified into two groups comparing the upper quartile ("Q4", n = 126) with the lower three quartiles ("Q1-3", n = 378). The primary outcome of our study was survival.. The "Q4" group included more men (46.8% vs. 34.9%, p = 0.017), had higher rates of atrial fibrillation (55.6% vs. 28.3%, p < 0.001) and showed features of more advanced aortic stenosis (mean pressure gradient 49 mmHg vs. 40 mmHg, aortic valve area 0.6 cm. NT-proBNP is associated with survival in TAVI patients with normal LVEF. In this patient group, preprocedural NT-proBNP levels do not only correlate with aortic stenosis, but reflect advanced cardiovascular dysfunction, including HFpEF, that might not be completely reversible after TAVI.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Echocardiography; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Predictive Value of Tests; Prognosis; Reproducibility of Results; Risk Assessment; Stroke Volume; Transcatheter Aortic Valve Replacement; Ventricular Function, Left

Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Registries; Stroke Volume; Transcatheter Aortic Valve Replacement

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment

Patients with a bicuspid aortic valve (BAV) are at risk of developing valve deterioration and aortic dilatation. We aimed to investigate whether blood biomarkers are associated with disease stage in patients with BAV.. Serum levels of high sensitivity C-reactive protein (hsCRP), high sensitivity troponin T (hsTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and total transforming growth factor-beta 1 (TGF-ß1) were measured in adult BAV patients with valve dysfunction or aortic pathology. Age-matched general population controls were included for TGFß-1 measurements. Correlation analyses and multivariable linear regression were used to determine the association between (2log-transformed) biomarker levels and aortic valve regurgitation, aortic valve stenosis, aortic dilatation, or left ventricular function.. Higher NT-proBNP and hsTNT levels were associated with aortic valve disease in BAV patients. TGF-ß1 levels were lower in BAV patients than in the general population, and not related to aortic dilatation. Longitudinal data are needed to further investigate the prognostic value of biomarkers in these patients.

Topics: Adult; Aortic Valve; Aortic Valve Disease; Aortic Valve Insufficiency; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Biomarkers; C-Reactive Protein; Dilatation, Pathologic; Female; Heart Disease Risk Factors; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Transforming Growth Factor beta1; Troponin T; Young Adult

The prognostic value of biomarkers in aortic stenosis (AS) remains understudied. We investigated whether a combination of biomarkers related to cardiovascular stress, inflammation, and damage is associated with mortality in patients with severe AS undergoing surgical aortic valve replacement (SAVR).. From a prospective registry of patients with severe AS referred for SAVR, 499 participants (mean age, 68 ± 8.5 years; 292 male) with available preoperative echocardiograms and biomarker data were included. Preoperative concentrations of NT-pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, and C-reactive protein were dichotomized as high or low, according to calculated cut-off values.. The mean follow-up time was 775 ± 410 days; 25 patients died. Only patients with elevated levels of all three biomarkers (n = 55) showed increased mortality [hazard ratio (HR), 7.26; 95% confidence interval (CI), 2.52-20.93; p < 0.001; reference group, no elevated biomarkers, n = 159]. Patients with elevated levels of the three biomarkers had higher 3-year all-cause mortality (24% vs. 4.5%); this remained true after multivariable adjustment (HR, 4.08; 95% CI, 1.87-8.87; p < 0.001). Patients with EuroSCOREs (logES) >3.0% tended to exhibit a higher risk of all-cause mortality (HR, 2.19; 95% CI, 0.98-4.87; p = 0.055); the mortality rate was 12-fold higher when logES >3 was combined with the three elevated biomarkers. This combination also showed a net reclassification improvement of 33% and significant likelihood-ratio test results.. A multiple biomarker approach might be useful for predicting postoperative mid-term mortality in patients with severe AS undergoing SAVR. Further large-scale prospective validation should be performed.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Biomarkers; C-Reactive Protein; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Registries; Risk Factors; Severity of Illness Index; Treatment Outcome; Troponin T

B-type natriuretic peptide (BNP) levels have been shown to predict outcomes in surgical aortic valve replacement patients. BNP levels have not been well studied in patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study is to define the utility of baseline BNP levels in predicting short-term outcomes after TAVI. In this retrospective, observational, study from 2012 to 2019, we reviewed data on 1297 low-risk, intermediate-risk and high-risk patients who underwent TAVI. Patients were dichotomized into those with baseline BNP levels above or below 500 pg/ml. Our primary outcome was a composite of inpatient stroke and death. Our secondary outcome was a composite of 30-day stroke, death and readmission. There were 975 patients with a baseline BNP level of <500 pg/ml and of those, 2% had our primary composite outcome and 13% of patients had our secondary composite outcome. There were 322 patients with a baseline BNP level of ≥500 pg/ml and of those, 6% had our primary composite outcome and 19% of patients had our secondary composite outcome. Those with a baseline BNP level ≥500 pg/ml were 3.47 times more likely (confidence of interval [CI] 1.727, 6.993, p = 0.0005) to have our primary composite outcome and were 1.72 times more likely (CI 1.186, 2.506, p = 0.0043) to have our secondary composite outcome. In conclusion, after adjustments for discrepant baseline characteristics, baseline BNP levels were independently predictive of a composite of inpatient stroke or death and a composite of 30-day stroke, death or readmission after TAVI. Those low, intermediate and high-risk patients whose baseline BNP is ≥500 pg/ml may ultimately require closer post-TAVI monitoring.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Retrospective Studies; Transcatheter Aortic Valve Replacement

The aim of this study was to investigate the preoperative prevalence, relation to symptoms, and prognostic implications of elevated left ventricular (LV) apical-to-basal strain ratio (ABr) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement.. A total of 499 contemporary consecutive patients with AS treated with transcatheter aortic valve replacement were retrospectively included. Patients were included if they underwent preoperative echocardiography with adequate image quality for assessment of LV global longitudinal strain. Baseline clinical and echocardiographic data were collected and analyzed in ABr subgroups. From two-dimensional echocardiographic apical images, ABr was calculated as mean longitudinal strain of the five LV apical segments divided by the mean of the six basal segments.. Median follow-up time was 743 days. Mean age was 79.8 ± 7 years. The prevalence of severely increased ABr ≥4 was 16% (n = 78). Patients with ABr ≥4 had higher preoperative New York Heart Association functional class; 77% of those with ABr ≥4 were in New York Heart Association functional class III or IV compared with 59% of those with ABr of 0 to 1.9 (P < .01). Median preoperative N-terminal pro-brain natriuretic peptide level in patients with ABr ≥4 was 1,781 pmol/L, compared with 876 pmol/L in those with ABr of 0 to 1.9 (P = .003). N-terminal pro-brain natriuretic peptide levels at 3-month follow-up remained considerably elevated in patients with ABr ≥4 (the median in patients with ABr ≥4 was 1,262 pmol/L vs 645 pmol/L in those with ABr of 0 to 1.9, P < .01). AS severity was comparable across ABr subgroup levels. Overall, increased ABr ≥4 was associated with poor survival, as overall 3-year survival was 67% among patients with ABr ≥4 compared with 83% in those with ABr of 2 to 3.9 and 86% in those with ABr of 0 to 1.9 (P = .04).. Among patients with increased ABr ≥4, pre- and postoperative New York Heart Association functional class, serum N-terminal pro-brain natriuretic peptide level, and mortality were significantly increased, and ABr may thus serve as a new echocardiographic marker of high mortality risk among patients with AS treated with transcatheter aortic valve replacement.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Prevalence; Prognosis; Retrospective Studies; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left

Risk stratification in patients post-transcatheter aortic valve replacement (TAVR) is limited to and is based on clinical judgment and surgical scoring systems. Serum natriuretic peptides are used for general risk stratification in patients with aortic stenosis, reflecting the increase in their afterload and thereby stressing the need for valve intervention. The objective of this study was to determine the predictive value of pre- and post-procedural serum brain natriuretic peptide (BNP) on 1-year all-cause mortality in patients who underwent TAVR.. In this population-based study, we included 148 TAVR patients treated at the Poriya Medical Center between June 1, 2015, and May 31, 2018. Routine blood samples for serum BNP levels (pg/mL) were taken just before the TAVR and 24 h post-TAVR. Our primary clinical outcome was defined as 1-year all-cause mortality. We used backward regression models and included all variables that had a p value <0.1 in the univariable analysis. A receiver-operating characteristic curve was calculated for the prediction of all-cause mortality by serum BNP levels using the median as the cut-off point.. In this study cohort, BNP levels 24 h post-TAVR higher than the cohort median versus lower than the cohort median (387.5 pg/mL; IQR 195-817.6) were the strongest predictor of 1-year mortality (hazard ratio 9; 95% CI 2.72-30.16; p < 0.001). The statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables.. Serum BNP levels 24 h post-procedure were found to be a meaningful marker in predicting 1-year all-cause mortality in patients after TAVR procedure.

Topics: Aortic Valve; Aortic Valve Stenosis; Cohort Studies; Humans; Natriuretic Peptide, Brain; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; ROC Curve; Symptom Assessment; Transcatheter Aortic Valve Replacement; Treatment Outcome

The 2017 European Society of Cardiology guidelines for valvular heart disease included changes in the definition of severe aortic stenosis (AS). We wanted to evaluate its influence on management decisions in asymptomatic patients with moderate-severe AS.. We reclassified the AS severity of the participants of the PRIMID-AS study (Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With AS), using the 2017 guidelines, determined their risk of reaching a clinical end point (valve replacement for symptoms, hospitalization, or cardiovascular death) and evaluated the prognostic value of aortic valve calcium score and biomarkers. Patients underwent echocardiography, cardiac magnetic resonance imaging, exercise tolerance testing, and biomarker assessment.. Of the 174 participants, 45% (56/124) classified as severe AS were reclassified as moderate AS. This reclassified group was similar to the original moderate group in clinical characteristics, gradients, calcium scores, and remodeling parameters. There were 47 primary end points (41 valve replacement, 1 death, and 5 hospitalizations-1 chest pain, 2 dyspnea, 1 heart failure, and 1 syncope) over 368±156 days follow-up. The severe and reclassified groups had a higher risk compared with moderate group (adjusted hazard ratio 4.95 [2.02-12.13] and 2.78 [1.07-7.22], respectively), with the reclassified group demonstrating an intermediate risk. A mean pressure gradient ≥31 mm Hg had a 7× higher risk of the primary end point in the reclassified group. Aortic valve calcium score was more prognostic in females and low valve area but not after adjusting for gradients. NT-proBNP (N-terminal pro-brain-type natriuretic peptide) and myocardial perfusion reserve were associated with the primary end point but not after adjusting for positive exercise tolerance testing. Troponin was associated with cardiovascular death or unplanned hospitalizations.. Reclassification of asymptomatic severe AS into moderate AS was common using the European Society of Cardiology 2017 guidelines. This group had an intermediate risk of reaching the primary end point. Exercise testing, multimodality imaging, and lower mean pressure gradient threshold of 31 mm Hg may improve risk stratification. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01658345.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Asymptomatic Diseases; Biomarkers; Cardiac Imaging Techniques; Clinical Decision-Making; Disease Progression; Exercise Test; Female; Heart Function Tests; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Multimodal Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Prospective Studies; Severity of Illness Index; Terminology as Topic; Troponin; United Kingdom

Transjugular intrahepatic portosystemic shunt (TIPS) is now a standard for the treatment of portal hypertension-related complications. After the TIPS procedure, incidence and risk factors of cardiac decompensation are poorly known. The main objectives were to measure the incidence of the onset of cardiac decompensation after TIPS and identify the predictive factors.. Hospitalization for cardiac decompensation is observed in 20% of patients in the year after TIPS insertion. Combining BNP or NT-proBNP levels and echocardiographic parameters should help improve patient selection.

Topics: Aged; Algorithms; Aortic Valve Stenosis; Echocardiography; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Portasystemic Shunt, Transjugular Intrahepatic; Prospective Studies

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Echocardiography; Feasibility Studies; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Preoperative Period; Prognosis; Prospective Studies; Reference Values; Risk Assessment; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome; Troponin I; Ventricular Dysfunction; Ventricular Function, Left

Topics: Aortic Valve Stenosis; Asymptomatic Diseases; Atrial Fibrillation; Biomarkers; Heart Valve Prosthesis Implantation; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Severity of Illness Index

Natriuretic peptide plasma levels help to manage patients with severe aortic stenosis (AS). The role of troponin plasma levels in this patient cohort remains speculative. A consortium of 4 university hospital centers in Austria analyzed retrospectively 3,595 patients admitted for valve replacement because of severe AS since 2007. The aim was to compare the additive preprocedural value of high-sensitivity troponin T (hsTnT) to N-terminal pro brain natriuretic peptide (NT-proBNP) plasma levels in predicting postoperative long-term survival in a large cohort undergoing either surgical (57.8%) or transcatheter (42.2%) aortic valve replacement. During a median follow-up of 2.93 (1.91 to 4.92) years, 919 patients (25.6%) died, in them 556 (15.5%) due to cardiovascular causes. Both normal hsTnT (<14 ng/l) and NT-proBNP (within age- and sex-corrected normal range) plasma levels were found in 481 patients (14.3%, group 1). Normal hsTnT but elevated NT-proBNP plasma levels were found in 748 patients (22.3%, group 2). Elevated hsTnT but normal NT-proBNP plasma levels were found in 258 patients (7.7%, group 3). Both elevated hsTnT and elevated NT-proBNP plasma levels were found in 1,869 patients (55.7%, group 4). Using Log Rank tests for comparison there was a highly significant difference in both cardiovascular mortality (p <0.0001) and all-cause mortality (p <0.0001). All-cause mortality rates after 1, 3, and 5 years were 2.1%, 5.4%, 7.7% in group 1; 4.0%, 7.5%, 11.5% in group 2; 5.8%, 8.9%, 14.0% in group 3; and 12.3%, 22.6%, 28.4% in group 4. In conclusion, hsTnT adds additional impact to NT-proBNP as a routinely available biomarker for risk stratification concerning postoperative survival in patients with severe AS admitted for valve replacement. The present study supports the concept to integrate hsTnT plasma levels in the management of severe AS.

Topics: Aged; Aortic Valve Stenosis; Austria; Biomarkers; Cohort Studies; Echocardiography, Doppler; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hospitals, University; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Preoperative Care; Prognosis; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Survival Rate; Time Factors; Treatment Outcome; Troponin T

N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels prior to transcatheter aortic valve implantation (TAVI) are known to be associated with outcomes of patients undergoing TAVI. However, little has been known about the NT-proBNP response after TAVI. Therefore, we aimed to clarify the role of the NT-proBNP response and identify the determinants of the NT-proBNP nonresponse among patients with severe aortic stenosis (AS) and heart failure (HF) undergoing TAVI. We examined 717 patients with severe AS and HF undergoing TAVI. NT-proBNP nonresponders were defined as patients whose NT-proBNP levels decreased by ≤ 30%. Mean NT-proBNP levels decreased from 7698 ± 7853 pg/mL (baseline) to 4523 ±  5173 pg/mL (post-TAVI); 269 patients (38%) were nonresponders. Female gender and prevalence of diabetes mellitus (DM), chronic kidney disease (CKD), atrial fibrillation (AF), and history of coronary artery revascularization were more common for NT-proBNP nonresponders. Permanent pacemaker implantation rate was higher for NT-proBNP nonresponders. In addition to the baseline NT-proBNP level > 7500 pg/smL (hazard ratio [HR], 1.8; p = 0.03), NT-proBNP nonresponse (HR 2.3; p = 0.001) was associated with lower survival rates. Baseline NT-proBNP level ≤ 7500 pg/mL (OR 3.2; p < 0.001), female gender (odds ratio [OR], 1.5; p = 0.049), DM (OR 1.6; p = 0.016), CKD (OR 1.8; p = 0.001), AF (OR 2.4; p < 0.001), history of coronary revascularization (OR 1.7; p = 0.003), and permanent pacemaker implantation after TAVI (OR 1.7; p = 0.034) were independent determinants of NT-proBNP nonresponse. In "conclusion", NT-proBNP response is important for long-term survival after TAVI. We should consider the aforementioned determinants, particularly permanent pacemaker implantation, as risk factors for NT-proBNP nonresponse.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Female; Germany; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Survival Analysis; Transcatheter Aortic Valve Replacement

Although careful monitoring of asymptomatic severe aortic stenosis (AS) is recommended to prevent missing the optimal timing of surgical or transcatheter aortic valve replacement, prophylactic treatment that could extend the asymptomatic period remains unknown. In a hypertensive population, high blood pressure (BP) measured at the doctor's office is known to be associated with B-type natriuretic peptide (BNP) level, a surrogate marker for symptomatic deterioration in AS. Little is known regarding the association between nocturnal BP variables and BNP in severe AS with preserved ejection fraction (EF). Methods and Results: The subjects consisted of 78 severe AS patients (mean age, 79±6 years) with preserved EF. Nocturnal BP was measured hourly using a home BP monitoring device. On multiple regression analysis, nocturnal mean systolic BP (SBP) remained independently associated with BNP after adjustment for age, sex, body mass index, estimated glomerular filtration rate, antihypertensive medication class, early diastolic mitral annular velocity, and left ventricular mass index (P=0.03), whereas diastolic BP (DBP) and variables of BP variability were not.. Higher nocturnal SBP rather than DBP or indices of BP variability was independently associated with BNP in AS patients with preserved EF. Intervention for nocturnal SBP may therefore extend the asymptomatic period and improve prognosis.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Systole

We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR).. We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50).. The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year.. Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy.. UMIN000012140.

Topics: Aged; Aortic Valve Stenosis; Asymptomatic Diseases; Biomarkers; Cause of Death; Echocardiography; Female; Heart Failure; Hospitalization; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Registries; Risk Assessment; Severity of Illness Index

Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Humans; Natriuretic Peptide, Brain

We aimed to assess longitudinal changes of B-type natriuretic peptide (BNP) in aortic stenosis (AS) patients treated by transcatheter aortic valve replacement (TAVR).. From our TAVR database, we identified 193 consecutive patients with severe symptomatic AS who underwent TAVR and were prospectively followed using serial BNP levels and echocardiography. Patients were divided into subgroups according to type of left ventricular (LV) remodeling as having normal LV mass and relative wall thickness, or showing concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH).. At baseline, 30 patients (16%) had EH, 115 (60%) had CH, 37 (19%) had CR, and 11 (6%) had normal LV geometry. After TAVR, BNP decreased in the first 30 days, with further improvement during follow-up. Patients with EH had higher BNP at baseline (P < 0.01) and a greater subsequent decrease (P < 0.001). During the median follow-up of 1331 days (interquartile range: 632-1678), 119 (62%) patients died. BNP showed a time-dependent association with all-cause mortality both in a univariable (hazards ratio [HR] 1.24, 95% confidence interval [CI]: 1.04-1.47, P = 0.017), and in a multivariable model with Society of Thoracic Surgeons score and baseline BNP forced into the analysis (HR 1.32, 95% CI: 1.001-1.73, P = 0.049). Elevated BNP was associated with a larger LV end-diastolic volume index (P < 0.001) and shorter 6-minute walk test distance (P = 0.013) throughout follow-up.. In patients with AS, BNP was associated with LV remodeling phenotypes and functional status before and after TAVR. Elevated BNP levels were associated with poor prognosis.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Echocardiography, Doppler; Exercise Tolerance; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Postoperative Period; Retrospective Studies; Stroke Volume; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

There is an ongoing debate regarding optimal management of patients with paradoxical low gradient severe aortic stenosis (PLG-SAS). We hypothesized that the presence of symptoms is closely associated with future adverse outcome. We aimed to determine the relation between symptoms and outcome in patients with PLG-SAS.. We prospectively enrolled 222 patients with PLG-SAS. Left ventricular (LV) volumes, mass, and strain were measured by three-dimensional echocardiography. The primary end-point was cardiac events including cardiac death, ventricular fibrillation, and heart failure leading to hospitalization.. There were 65 cases of symptomatic PLG-SAS and 157 cases of asymptomatic PLG-SAS. Patients with symptomatic PLG-SAS received beta-blockers, angiotensin blockers, and diuretics more frequently and showed higher levels of B-type natriuretic peptide than patients with asymptomatic PLG-SAS. Although LV chamber parameters were not different, patients with symptomatic PLG-SAS had significantly higher E-wave velocity and E/A ratio than patients with asymptomatic PLG-SAS. During the median follow-up of 18 months, 20 patients reached the primary end-point. Patients with symptomatic PLG-SAS had significantly worse prognosis than patients with asymptomatic PLG-SAS. A similar trend was observed while comparing with the propensity-score-matched cohort after adjusting for age, sex, stroke volume index, and severity of AS.. Symptomatic PLG-SAS is associated with poorer prognosis even after adjusting for flow status and severity of AS. Therefore, presence of symptoms is not always related to the severity of AS itself but might be related to the underlying comorbidities. Our results suggest a possible link between PLG-SAS and heart failure with preserved ejection fraction in some symptomatic patients.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography, Three-Dimensional; Female; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Propensity Score; Prospective Studies; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Background Cardiovascular biomarkers constitute promising tools for improved risk stratification and prediction of outcome in patients undergoing transcatheter aortic valve implantation. We examined the association of periprocedural changes of NT-proBNP (N-terminal pro-B-type natriuretic peptide) with survival after transcatheter aortic valve implantation. Methods and Results NT-proBNP levels were measured in 704 patients before transcatheter aortic valve implantation and at discharge. Patients were grouped as responders and nonresponders depending on an NT-proBNP-based ratio (postprocedural NT-proBNP at discharge/preprocedural NT-proBNP). Overall, 376 of 704 patients showed a postprocedural decrease in NT-proBNP levels (NT-proBNP ratio <1). Responders and nonresponders differed significantly regarding median preprocedural (2822 versus 1187 pg/mL, P<0.001) and postprocedural (1258 versus 3009 pg/mL, P<0.001) NT-proBNP levels. Patients in the nonresponder group showed higher prevalence of atrial fibrillation (47.0% versus 39.4%, P=0.042), arterial hypertension (94.2% versus 87.5%, P=0.002), renal impairment (77.4% versus 69.1%, P=0.013), and peripheral artery disease (24.4% versus 14.6%, P=0.001). In contrast, patients in the responder group had higher prevalence of moderately reduced left ventricular ejection fraction (17.3% versus 11.0%, P=0.017), lower calculated aortic valve area (0.7 versus 0.8 cm

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Female; Follow-Up Studies; Germany; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Preoperative Period; Protein Precursors; Retrospective Studies; Survival Rate; Transcatheter Aortic Valve Replacement

Severe aortic stenosis (AS) is considered as an independent risk factor for perioperative cardiac complications of non-cardiac surgery. Surgical aortic valve replacement should be considered before non-cardiac surgery in patients with symptomatic severe AS. However, recently, transcatheter aortic valve replacement (TAVR) has emerged as an alternative approach for selected AS patients. We sought to determine the safety and efficacy of TAVR in preparation for major non-cardiac surgery. From our retrospective database, seven patients who underwent TAVR in preparation for major non-cardiac surgery were identified, and their clinical and hemodynamic data were collected. After TAVR, a significant reduction in the mean transaortic pressure gradient from 54.0 (Interquartile range (IQR) 47.5-64.5) to 18.0 (IQR 12.5-19.0) mmHg (p = 0.016) and an increase in the calculated aortic valve area from 0.6 (IQR 0.6-0.7) to 1.3 (IQR 1.1-1.5) cm

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Retrospective Studies; Transcatheter Aortic Valve Replacement

Transcatheter aortic valve implantation (TAVI) is an alternative therapeutic option for severe aortic stenosis. Aortic regurgitation (AR) is commonly observed after TAVI and increases the mortality rate. We hypothesized that the influence of significant AR, defined as that more severe than mild AR, on survival rate after TAVI might differ according to the baseline left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) level. We categorized 856 patients who underwent transfemoral TAVI into 2 groups according to their baseline LVEF (<40 and ≥40%) and NT-pro BNP levels (≤5000 and >5000 pg/mL). Significant AR was observed in 92 patients (11%). Among patients with significant AR, the proportion of patients with CoreValve/EvolutR implantation was higher than that of patients with SAPIEN XT/3 implantation. Kaplan-Meier curves and the log-rank test showed that significant AR was not associated with 1-year mortality in patients with LVEF ≥40% and those with NT-pro BNP level ≤5000 pg/mL. On the other hand, it was significantly associated with a higher 1-year mortality in patients with LVEF <40% (p = 0.003) and those with NT-pro BNP level >5000 pg/mL (p = 0.011). Similarly, multivariate Cox regression analysis showed that the presence of AR was significantly associated with a higher 1-year mortality in patients with LVEF <40% [p = 0.005, hazard ratio (HR) = 3.626] and NT-pro BNP level >5000 pg/mL (p = 0.004, HR = 3.221). However, AR was not significantly associated with a higher 1-year mortality in patients with LVEF ≥40% and NT-pro BNP level ≤5000 pg/mL. Thus, the impact of significant AR on mortality after TAVI seems to be considerable in patients with reduced LVEF or high NT-pro BNP levels, but not those with preserved LVEF or low NT-pro BNP levels, suggesting that the influence of AR differs depending on the baseline LVEF and NT-pro BNP level.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Aortography; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Stroke Volume; Survival Rate; Transcatheter Aortic Valve Replacement

Topics: Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Risk Assessment; Stroke Volume; Troponin

Elevated carbohydrate antigen 125 (CA125) and N-terminal pro-brain natriuretic peptide (NTproBNP) have been associated with adverse outcome after transcatheter aortic valve implantation (TAVI). This study performs a comparison of both biomarkers for prognosis after TAVI. The study includes 363 patients. The primary end point was all-cause death or readmission for worsening congestive heart failure within 1 year after TAVI, and this end point occurred in 16% of the population. The optimal cutoff to predict the primary end point was 18.4 U/ml for CA125 and 2,570 ng/L for NTproBNP. Elevated CA125 levels were present in 52% and were associated with a higher rate of the primary end point (27% vs 3%; p <0.001). In parallel, elevated NTproBNP levels were present in 42% and were also associated with a higher rate of the primary end point (27% vs 8%; p <0.001). After multivariable adjustment, elevated CA125 (hazard ratio [HR] 5.26; p <0.001) and elevated NTproBNP (HR 2.12; p = 0.022) were independent predictors of the primary end point. To explore the utility of combining both biomarkers, CA125 was added to the model containing baseline variables and NTproBNP. Elevated CA125 (HR 4.62; p = 0.001), but not NTproBNP (HR 1.58; p = 0.194), persisted as an independent predictor of the primary end point. Addition of CA125 significantly improved the predictive capability of the model (C-statistic: 0.805 vs 0.776) and the net reclassification index (50%, 95% confidence interval [20 to 84]) with an integrated discriminative improvement of 3.0%. In conclusion, elevated CA125 and NTproBNP predict adverse clinical outcome after TAVI. However, when combining both biomarkers, the predictive capacity of CA125 was superior.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; CA-125 Antigen; Female; Germany; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Transcatheter Aortic Valve Replacement

Fetal aortic stenosis (AS) imposes pressure load on the developing left ventricle (LV) and leads to derangements in myocardial structure and function via mechanisms that are not well characterized.. We compared amniotic fluid NT-BNP and troponin levels in fetuses with AS prior to fetal valvuloplasty and controls. We estimated correlations between NT-BNP and fetal echo parameters and identify NT-BNP cutoff associated with biventricular outcome RESULTS: Median NT-BNP level was higher in fetal AS than controls (3858 vs 1737 pg/mL, P < 0.012). By contrast, troponin levels were lower in fetal AS, with troponin > detectable in 0/25 (0%) AS cases compared with 22/85 (26%) controls (P = 0.03). Of 25 fetal AS cases, 12 (48%) had biventricular outcome. Fetuses with NT-BNP < 910 pg/mL were more likely to have biventricular (OR =10) compared with those ≥910 pg/mL (P = 0.045). Higher NT-BNP correlated with earlier gestational age and measures of larger left heart size.. NT-BNP is elevated in fetal AS, suggesting that LV pressure load and increased wall stress lead to maladaptive stretch-related myocardial remodeling. Troponin is normal in mid-gestation fetal AS, suggesting that ischemia is not the primary factor in fetal response to LV pressure load.

Topics: Amniotic Fluid; Aortic Valve Stenosis; Female; Fetal Diseases; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Retrospective Studies; Troponin; Ventricular Remodeling

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Severity of Illness Index

The aim of this study was to investigate the 2-year prognostic impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at discharge following transcatheter aortic valve implantation (TAVI).. Multicentre prospective observational study.. Seven institutions from multicentre, observational registry of symptomatic patients with severe aortic stenosis who undergo TAVI.. We enrolled 500 consecutive patients who underwent TAVI with measurements of NT-proBNP at discharge between 2013 and 2016. Study patients were stratified into two groups according to survival classification and regression tree (CART) analysis: high versus low NT-proBNP groups.. The impact of high NT-proBNP on a 2-year composite endpoint consisting of all-cause mortality and heart failure hospitalisation was evaluated using a multivariable Cox model.. Elevation of NT-proBNP at discharge is associated with higher incidence of the 2-year composite endpoint after TAVI.. 000020423.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Female; Heart Failure; Hospitalization; Humans; Incidence; Japan; Male; Mortality; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Prognosis; Prospective Studies; Registries; Transcatheter Aortic Valve Replacement

Transcatheter aortic valve implantation (TAVI) is an emerging minimally invasive treatment modality in high surgical risk or inoperable patients.. The aim of this study was to ascertain the effect of TAVI on left ventricular (LV) systolic and diastolic function and serum B-type natriuretic peptide (BNP) levels in high surgical risk or inoperable patients with severe aortic stenosis.. Fifty-five patients were included in our retrospective study. LV systolic and diastolic function was assessed with conventional and tissue Doppler imaging (TDI) prior to and after TAVI. Additionally, BNP was measured 24 h before and three months after the procedure. Echocardiographic controls were performed at one, three and six months and one year and mean values were taken. At the end of the study, LV systolic and diastolic function, serum BNP levels and New York Heart Association functional capacity were assessed and compared to baseline parameters.. We found that LV structural changes and diastolic dysfunction occur in patients with severe aortic stenosis and that TAVI is able to reverse these abnormalities, which we demonstrated by both conventional echocardiography and TDI. In addition, serum BNP levels were decreased after TAVI.

Topics: Aged; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Retrospective Studies; Risk Assessment; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Ventricular Function, Left

Among patients with severe aortic stenosis (AS), we investigated the associations of N-terminal pro-natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), and high-sensitive C-reactive protein (hs-CRP) with 3-year mortality and major adverse cardiovascular events (MACE) during 1 year.. This observational cohort study prospectively enrolled 442 patients with severe AS who were referred for evaluation of possible valve replacement. Clinical data was recorded before the decision of whether to operate was made. We studied the prognostic value of assessing biomarkers by serum levels, and tested associations of NT-proBNP, hsTnT, and hs-CRP with clinical outcomes (3-year all-cause mortality and risk of MACE in the year following study inclusion) using adjusted multivariable analysis.. Elevated serum levels of these biomarkers at baseline evaluation were associated with increased all-cause 3-year mortality regardless of treatment assignment. Adjusted analysis showed that none of the studied biomarkers (NT-proBNP, hsTnT or hs-CRP) or any other covariates were associated with 3-year all-cause mortality following surgical aortic valve replacement (SAVR). However, adjusted analyses showed that hsTnT (HR, 1.51; 95% CI, 1.11-2.05; P = 0.008) and left ventricular ejection fraction (HR 0.97; 95% CI 0.94-0.97, P = 0.043) was associated with MACE for operated patients.. Whereas NT-proBNP, hsTnT and hs-CRP had no independently prognostic value in relation to all-cause mortality following SAVR, hsTnT was independently associated with MACE following operation. The use of these clinically available biomarkers, in particular hsTnT, should be clarified in larger studies.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; C-Reactive Protein; Cause of Death; Comorbidity; Female; Hemodynamics; Humans; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Troponin T

Topics: Aortic Valve Stenosis; Coronary Circulation; Humans; Microcirculation; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments

In this study, we sought to investigate the 2-year prognostic impact of B-type natriuretic peptide (BNP) levels at discharge, following transcatheter aortic valve replacement.. We enrolled 1094 consecutive patients who underwent transcatheter aortic valve replacement between 2013 and 2016. Study patients were stratified into 2 groups according to survival classification and regression tree analysis (high versus low BNP groups). We evaluated the impact of high BNP on 2-year mortality compared with that of low BNP using a multivariable Cox model, and assessed whether this stratification would improve predictive accuracy for determining 2-year mortality by assessing time-dependent net reclassification improvement and integrated discrimination improvement. The median age of patients was 85 years (quartile 82-88), and 29.2% of the study population were men. The median Society of Thoracic Surgeons score was 6.8 (4.7-9.5), and BNP at discharge was 186 (93-378) pg/mL. All-cause mortality following discharge was 7.9% (95% CI, 5.8-9.9%) at 1 year and 15.4% (95% CI, 11.6-19.0%) at 2 years. The survival classification and regression tree analysis revealed that the discriminating BNP level to discern 2-year mortality was 202 pg/mL, and that elevated BNP had a statistically significant impact on outcomes, with an adjusted hazard ratio of 2.28 (1.36-3.82,. Elevation of BNP at discharge is associated with 2-year mortality after transcatheter aortic valve replacement.

Topics: Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Chi-Square Distribution; Female; Humans; Japan; Kaplan-Meier Estimate; Linear Models; Logistic Models; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Patient Discharge; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Severity of Illness Index; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Up-Regulation

Once aortic stenosis (AS) is severe, patients develop symptoms at different stages. Indeed, symptom status may correlate poorly with the grade of valve narrowing. Multiple pathophysiological mechanisms, other than valvular load, may explain the link between AS and symptom severity. We aimed to describe the relationship between the severity of symptoms and the characteristics of a cohort of patients with severe AS already referred for aortic valve replacement (AVR).. We analyzed 118 consecutive patients (70±9 years, 55% men) with severe AS referred for AVR. We identified 84 patients with New York Heart Association (NYHA) I-II, and 34 with NYHA III-IV symptoms. Clinical and echocardiographic parameters were compared between these two groups. Left ventricular ejection fraction (LVEF), global longitudinal peak systolic strain (GLPS), NT-pro-B-type natriuretic peptide (BNP), and high-sensitive troponin T (hs-TNT) were determined at the time of admission.. AS severity was similar between groups. Compared with the NYHA I-II group, patients in NYHA III-IV group were older and more likely to have comorbidities, worse intracardiac hemodynamics and more LV damage. Variables independently associated with NYHA III-IV symptomatology were the absence of sinus rhythm, higher E/e' ratio, and increased hs-TNT. GLPS showed a good correlation not only with hs-TNT as a marker of myocardial damage, but also with markers of increased afterload imposed on LV, being not directly related with advanced symptoms.. Advanced symptoms in patients with severe AS referred for AVR are associated with worse intracardiac hemodynamics, absence of sinus rhythm, and more myocardial damage. It supports the concept of transition from adaptive LV remodeling to myocyte death as an important determinant of symptoms of heart failure.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Echocardiography; Female; Heart; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Symptom Assessment; Troponin T; Ventricular Function, Left

Tissue Doppler imaging (TDI) and N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP) provides useful non-invasive information about left ventricle filling pressures and both have demonstrated to be a prognostic marker in some valve disease as aortic stenosis (AS).. To assess the clinical value of combined TDI and NT-proBNP information in asymptomatic AS patients.. Prospective study of 350 initially asymptomatic moderate to severe AS patients with: Mean aortic valve area 0.8 (0.3) cm. After a mean follow-up of 29 (10) months, 165 (47%) patients suffered some clinical event. In order to predict clinical events, Bootstrap analysis determined the best cut-point value: E/E' ratio higher than 13 and NT-proBNP higher than 515pg/mL. E/E' ratio provides more specificity (78.9% vs 55.9%) and NT-proBNP provides more sensitivity (76.6% vs 43.7%). Combined use of both parameters provides the best prognostic information (sensitivity 75.6%, specificity 67.2%, negative predictive value 82.1%, positive predictive value 57.5%, accuracy 71.4%).. Combined use of TDI and natriuretic peptides information provides incremental prognostic value and is a useful tool to predict the prognosis in asymptomatic AS patients.

Topics: Aged; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; ROC Curve; Survival Analysis

The prognostic value of N-terminal fragment of pro B-type natriuretic peptide (Nt-proBNP) in aortic stenosis (AS) is still being debated. We sought to evaluate the determinants of Nt-proBNP in AS and its prognostic value in asymptomatic patients.. Patients with pure isolated at least mild degenerative AS enrolled in our prospective cohort (2006-2013) constituted our population. Clinical and biological measurements as well as echocardiographic evaluations were performed at study entry for all patients. Severe AS was defined by a valve area <1cm. We enrolled 809 patients. Nt-proBNP increased with AS severity (p<0.0001) and symptomatic status (p<0.0001) but there was a wide overlap between groups of AS severity or symptomatic status. Nt-proBNP was the result of complex interactions between multiple determinants, including AS severity and symptomatic status but also age (p=0.0008), history of coronary artery disease (p=0.03), rhythm (p=0.007) and diastolic function (p<0.0001). Consequently, in asymptomatic patients with moderate/severe AS, normal ejection fraction and in sinus rhythm, Nt-proBNP was associated with AS-related events in univariate analysis (p=0.009) but not after adjustment for AS severity (p=0.12). Repeated Nt-proBNP measurements at one year did not improve their predictive value (p=0.43).. This study highlights the limitations of Nt-proBNP in AS and raises caution regarding its use, at least as a single factor, in the decision-making process regarding asymptomatic patients with AS.

Topics: Age Factors; Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cohort Studies; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Severity of Illness Index; Sex Factors

Subcutaneous implantable electrocardiographs are highly effective in detecting covert atrial fibrillation (AF) in cryptogenic stroke. However, these invasive devices are not indicated for all cryptogenic stroke patients, and noninvasive improvements over conventional Holter-type ambulatory electrocardiography are needed. We evaluated the clinical application and effectiveness of Duranta (ImageONE Co., Ltd.), a wireless patch-type electrocardiographic monitoring system developed in Japan for chronically ill patients or home-based patients at the end of life. A Duranta device was used to detect covert AF in patients with acute ischemic stroke of undetermined source with no sign of AF during cardiographic monitoring ≥24 hours postadmission.. A 72-year-old man with severe aortic stenosis was admitted to our hospital with dysarthria and right upper limb weakness. Diffusion-weighted plain head magnetic resonance imaging (MRI) showed acute cerebral infarctions across the left middle cerebral artery territory. Twelve-lead electrocardiography, Holter-type ambulatory electrocardiography, and cardiographic monitoring for ≥24 hours revealed no AF, indicating a probable diagnosis of artery-to-artery embolism following left common carotid artery stenosis detected by carotid ultrasound imaging and cerebral angiography.. However, because of high blood brain natriuretic peptide (BNP) and valvular heart disease, continuous monitoring using Duranta was performed from the 2nd to 13th days after onset to exclude possible cardioembolic stroke. Waveform and heart rate trend graph analysis showed paroxysmal AF (PAF) occurred on the 5th and 9th days after onset. PAF did not occur at any other time during the observation period. The quality of the cardiograms sufficed for analysis and diagnosis of AF. The lightweight compact device can be placed quickly with no movement restriction. These features and our findings show the usefulness of the Duranta device for long-term continuous monitoring.. A noninvasive wireless patch-type electrocardiographic monitoring system, Duranta, placed at the precordium, was useful in detecting covert AF in cryptogenic stroke patients, warranting further investigation.

Topics: Acute Disease; Aged; Aortic Valve Stenosis; Atrial Fibrillation; Brain Ischemia; Carotid Stenosis; Electrocardiography, Ambulatory; Humans; Male; Natriuretic Peptide, Brain; Stroke

We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure.. Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as C. Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the C. These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomechanical Phenomena; Blood Flow Velocity; Collagen Type I; Collagen Type III; Diastole; Elastic Modulus; Extracellular Matrix; Female; Heart Failure; Humans; Immunohistochemistry; Male; Microscopy, Atomic Force; Microscopy, Confocal; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Stroke Volume

The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with ≥ moderate aortic stenosis (AS) and preserved left ventricular ejection fraction.. We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death.. During a follow-up of 30 ± 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 ± 9 vs 65 ± 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 ± 0.6 vs 3.5 ± 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 ± 2.5 vs 8.7 ± 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 ± 155 vs +7 ± 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 ± 8% vs 97 ± 3%; 3 years: 31 ± 8% vs 68 ± 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters.. In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement.

Topics: Aged; Aortic Valve Stenosis; Asymptomatic Diseases; Biomarkers; Disease Progression; Disease-Free Survival; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Stroke Volume; Time Factors; Ventricular Function, Left

Topics: Aortic Valve Stenosis; Female; Humans; Male; Natriuretic Peptide, Brain; Risk Assessment; Stroke Volume; Ventricular Function, Left

In aortic stenosis (AS), symptoms and left ventricular (LV) dysfunction represent a later disease state, and objective parameters that identify incipient LV dysfunction are needed. We sought to determine prognostic utility of brain natriuretic peptide (BNP) and left ventricular global longitudinal strain (LV-GLS) in patients with aortic valve area <1.3 cm(2).. Five-hundred and thirty-one patients between January 2007 and December 2008 with aortic valve area <1.3 cm(2) (86% with aortic valve area ≤1.1 cm(2)) and left ventricular ejection fraction ≥50% who had BNP drawn ≤90 days from initial echo were included. Society of Thoracic Surgeons (STS) score and mortality were recorded. Mean STS score, glomerular filtration rate, and median BNP were 11±5, 73±35 mL/min per 1.73 m , and 141 (60-313) pg/mL, respectively; 78% were in New York Heart Association class ≥II. Mean LV-stroke volume index (LV-SVI) and LV-GLS were 39±10 mL/m(2) and -13.9±3%. At 4.7±2 years, 405 patients (76%) underwent aortic valve replacement; 161 died (30%). On multivariable survival analysis, age (hazard ratio [HR] 1.46), New York Heart Association class (HR 1.27), coronary artery disease (HR 1.72), decreasing glomerular filtration rate (HR 1.15), increasing BNP (HR 1.16), worsening LV-GLS (HR 1.13) and aortic valve replacement (time dependent) (HR 0.34) predicted survival (all P<0.01). For mortality, the c-statistic incrementally increased as follows (all P<0.01): STS score (0.60 [0.58-0.64]), STS score+BNP (0.67 [0.62-0.70]), and STS score+BNP+LV-GLS (0.74 [0.68-0.78]).. In normal LVEF patients with significant aortic stenosis, BNP and LV-GLS provide incremental (additive not duplicative) prognostic information over established predictors, suggesting that both play a synergistic role in defining outcomes.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Severity of Illness Index; Stress, Mechanical; Stroke Volume; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left

Aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) are both frequent in elderly. The combination of these two diseases has never been investigated.. To describe patients with concomitant AS and TTR-CA.. Six cardiologic French centres identified retrospectively cases of patients with severe or moderate AS associated with TTR-CA hospitalized during the last 6 years.. Sixteen patients were included. Mean ± SD age was 79 ± 6 years, 81% were men. Sixty per cent were NYHA III-IV, 31% had carpal tunnel syndrome, and 56% had atrial fibrillation. Median (Q1;Q4) NT-proBNP was 4382 (2425;4730) pg/mL and 91% had elevated cardiac troponin level. Eighty-eight per cent had severe AS (n = 14/16), of whom 86% (n = 12) had low-gradient AS. Mean ± SD interventricular septum thickness was 18 ± 4 mm. Mean left ventricular ejection fraction and global LS were 50 ± 13% and -7 ± 4%, respectively. Diagnosis of TTR-CA was histologically proven in 38%, and was based on strong cardiac uptake of the tracer at biphosphonate scintigraphy in the rest. Eighty-one per cent had wild-type TTR-CA (n = 13), one had mutated Val122I and 19% did not had genetic test (n = 3). Valve replacement was surgical in 63% and via transcatheter in 13%. Median follow-up in survivors was 33 (16;65) months. Mortality was of 44% (n = 7) during the whole follow-up period.. Combination of AS and TTR-CA may occur in elderly patients particularly those with a low-flow low-gradient AS pattern and carries bad prognosis. Diagnosis of TTR-CA in AS is relevant to discuss specific treatment and management.

Topics: Aged; Amyloid Neuropathies, Familial; Aortic Valve Stenosis; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Stroke Volume; Treatment Outcome

Transcatheter aortic valve implantation improves survival in patients with severe aortic stenosis who are ineligible for surgical valve replacement; however, not all patients benefit from the procedure. We endeavoured to identify these patients using intraoperative echocardiography and hypothesized that intraoperative left ventricular function in response to the acute afterload reduction during the procedure was related to long-term outcomes.. We prospectively included 64 patients who were scheduled for transcatheter aortic valve implantation and divided them into responders and non-responders based on their left ventricular intraoperative responses to the acute afterload reduction after valve deployment. Responders were defined by increases of ≥20% in left ventricular longitudinal peak systolic velocities determined by tissue Doppler echocardiography. All patients were assessed for the following outcomes at 12 months: cardiac mortality, adverse cardiac events, quality of life, New York Heart Association class, N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiography.. Thirty-five patients (55%) were classified as responders and 29 patients (45%) as non-responders. Compared with responders, non-responders had higher risks of death (28 vs 9%, respectively, P = 0.04) and cardiac events (66 vs 26%, respectively, P < 0.01) during the 12-month follow-up. Significant long-term improvements in quality of life, NT-proBNP and left ventricular function were observed only in the responders. Preoperative risk stratification, intraoperative handling, aortic gradient and valve area were similar between groups.. Intraoperative assessment of left ventricular function by tissue Doppler echocardiography predicted long-term outcomes after transcatheter aortic valve implantation. Our results suggest that a preoperative test of myocardial contractile reserve might improve risk stratification and patient selection prior to the procedure.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Humans; Male; Monitoring, Intraoperative; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left

In Western countries heart disease is the leading cause of maternal death during pregnancy. The effect of pregnancy on the heart is difficult to study in patients with preexisting heart disease. Since experimental studies are scarce, we investigated the effect of pressure overload, produced by transverse aortic constriction (TAC) in mice, on the ability to conceive, pregnancy outcome, and maternal cardiac structure and function. Four weeks of TAC produced left ventricular (LV) hypertrophy and dysfunction with marked interstitial fibrosis, decreased capillary density, and induced pathological cardiac gene expression. Pregnancy increased relative LV and right ventricular weight without affecting the deterioration of LV function following TAC. Surprisingly, the TAC-induced increase in relative heart and lung weight was mitigated by pregnancy, which was accompanied by a trend towards normalization of capillary density and natriuretic peptide type A expression. Additionally, the combination of pregnancy and TAC increased the cardiac phosphorylation of c-Jun, and STAT1, but reduced phosphoinositide 3-kinase phosphorylation. Finally, TAC did not significantly affect conception rate, pregnancy duration, uterus size, litter size, and pup weight. In conclusion, we found that, rather than exacerbating the changes associated with cardiac pressure overload, pregnancy actually attenuated pathological LV remodeling and mitigated pulmonary congestion, and pathological gene expression produced by TAC, suggesting a positive effect of pregnancy on the pressure-overloaded heart.

Topics: Animals; Animals, Newborn; Aortic Valve Stenosis; Atrial Natriuretic Factor; Birth Weight; Capillaries; Disease Models, Animal; Echocardiography; Female; Fibrosis; Hypertrophy, Left Ventricular; Litter Size; Mice; Mice, Inbred C57BL; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Phosphatidylinositol 3-Kinases; Phosphorylation; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Rate; Proto-Oncogene Proteins c-jun; Real-Time Polymerase Chain Reaction; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; STAT1 Transcription Factor; Time Factors; Transcriptome; Ventricular Dysfunction, Left

INTRODUCTION The effect of asymptomatic severe aortic stenosis (ASAS) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels ar rest and during exercise, as well as their relevance for clinical practice remain controversial.  OBJECTIVES The aim of this study was to test the hypothesis of whether the evaluation of NT-proBNP concentrations during exercise provides additional information about the severity of aortic stenosis and left ventricular remodeling in patients with ASAS. PATIENTS AND METHODS A total of 50 patients with ASAS (mean age, 38.4 ±18.1 years) and 21 healthy subjects (mean age, 43.4 ±10.6 years) were enrolled. Rest and exercise echocardiography was performed to evaluate maximum velocity (Vmax), mean aortic gradient (AG), and aortic valve area (AVA). The left ventricular mass index (LVMI) was calculated. NT-proBNP concentrations at rest and during exercise were assessed, and the difference between the 2 values was calculated (ΔNT-proBNP). RESULTS NT-proBNP and ΔNT-proBNP levels at rest and during exercise were significantly higher in the ASAS group compared with the control group. In the ASAS group, NT-proBNP levels at rest significantly correlated with LVMI (r = 0.432; P <0.0001), AVA (r = -0.408; P <0.0001), Vmax (r = 0.375; P = 0.002), and mean AG (r = 0.257; P = 0.03). NT-proBNP levels during exercise significantly correlated with LVMI (r = 0.432; P <0.0001), mean AG (r = 0.401; P = 0.001), and AVA (r = -0.375; P = 0.001). In the multivariate logistic regression model, the factors independently associated with NT-proBNP both at rest and during exercise were age, AVA, and LVMI. CONCLUSIONS NT-proBNP levels at rest provide valuable information for identifying patients with more advanced left ventricular hypertrophy secondary to severe aortic stenosis. NT-proBNP levels during exercise do not provide new information on the severity of AS.

Topics: Adult; Aortic Valve Stenosis; Exercise; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Ventricular Remodeling; Young Adult

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Registries; Retrospective Studies; Severity of Illness Index; Transcatheter Aortic Valve Replacement

There is accumulating evidence that up to 20% of the implanted devices after TAVI are associated with a significant degree of paravalvular leaks, which appear to be associated with a negative clinical outcome.. A total of 355 patients with severe aortic valvular stenosis (AVS) were treated by TAVI (Corevalve n = 222, Edwards Sapien n = 133). Survival, NT-proBNP and the grade of PVL were quantified up to 12 months after implantation.. Technical success rate was 97.8%. Thirty-day mortality was 9.6%. Post-procedural transvalvular aortic regurgitation was seen only in a minority of cases (5%), whereas PVL were frequently observed (grade: <1+ in 58.2%, ≥1-<2 in 33.9%, and ≥2 in 7.9%). There was a clear relation-ship between PVL and adverse outcome (P < 0.001). After a transient increase, NT-proBNP showed a significant decline. Interestingly, a PVL ≥2+ was associated with a much higher rise in NT-proBNP compared to the other groups (P < 0.01), and a post-procedural increase in NT-proBNP by more than 1640 ng L(-1) within 5 days was associated with a significant increase in rate of death (P < 0.01).. TAVI is an efficient treatment option for high-risk patients with severe AVS. The incidence of PVL is an inacceptable clinical problem. Serial measurement of NT-proBNP can be used for risk-stratification in patients with a significant PVL. In general, PVL graded ≥2+ is associated with a dramatically increased 6-month mortality. Therefore, any action to reduce paraprosthetical regurgitation is highly recommended.

Topics: Aged; Aged, 80 and over; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Cardiac Catheterization; Female; Germany; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Prosthesis Failure; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome

We aimed to assess the impact of B-type natriuretic peptide (BNP) on short-term outcomes in patients undergoing transcatheter aortic valve implantation (TAVI).. Of 500 consecutive patients with severe aortic stenosis undergoing TAVI at our institution, we studied 340 patients who had a BNP assessment prior to TAVI. Patients were divided into tertiles - low: BNP ≤201 pg/mL (n=114), mid: BNP 202-595 pg/mL (n=113) and high: BNP ≥596 pg/mL (n=113). The primary endpoint was all-cause mortality, cardiac death and major adverse cardiac and cerebrovascular events (MACCE; death, major stroke and myocardial infarction) at 30 days. Compared with low tertile, high tertile patients were at higher baseline surgical risk (STS score 5.5±3.0 vs. 7.4±4.1, p=0.002). On echocardiography, high tertile patients had smaller valve areas (0.74±0.21 vs. 0.66±0.23 cm², p=0.008), higher left ventricular (LV) mass indices (123.40±33.66 vs. 168.22±47.96 g/m², p<0.001) and lower LV ejection fractions (61.59±7.18 vs. 42.65±15.41%, p<0.001) as compared with low tertile patients. At 30 days, a significantly higher incidence of death (hazard ratio [HR] 7.41, p=0.001) cardiac death (HR 5.82, p=0.006) and MACCE (HR 9.04, p<0.001) was observed among high as compared to low tertile patients.. In TAVI patients, higher BNP values at baseline are associated with an increased risk for an adverse event periprocedurally and after 30 days, respectively.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Cardiovascular Diseases; Cohort Studies; Databases, Factual; Female; Humans; Incidence; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Retrospective Studies; Severity of Illness Index; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome

Identification of heart failure (HF) symptoms in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF) is clinically important, but assessment of HF symptoms is challenging. It was recently reported that resting left atrium (LA) functions are related to exercise performance and are also important prognostic markers for patients with HF. The aim of this study was to assess the association of the HF symptoms with LA function in patients with severe AS and preserved LVEF.. We retrospectively studied 40 patients with severe AS and preserved LVEF (all ≥50%) who were referred for aortic valve replacement (AVR). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle tracking longitudinal strain rate from apical four- and two-chamber views. Twenty patients were symptomatic and 20 asymptomatic.. Aortic stenosis severity was similar for the 2 groups. Symptomatic status was associated with age, LV mass index, hemoglobin, B-type natriuretic peptide, LV end-systolic volume index, LVEF, LA volume index, SR-LAs, SR-LAe, and SR-LAa. Importantly, multivariate logistic regression analysis revealed that SR-LAa was the only independent determinant of symptomatic status (OR = 0.242, P = 0.002). Furthermore, significant improvement of SR-LAa was observed along with the reduction in LA volume index and LV mass index after AVR.. SR-LAa was found to be associated with the HF symptoms. Characterization of LA booster-pump function may be useful for the assessment of the symptomatic status in patients with severe AS patients and limited physical activity.

Topics: Age Factors; Aged; Aortic Valve Stenosis; Atrial Function, Left; Female; Heart Atria; Heart Failure; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Retrospective Studies; Severity of Illness Index; Ultrasonography; Ventricular Function, Left

We studied the prognostic value of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP)-ratio, which is independent of individual cutoff levels, in predicting mortality in patients undergoing transcatheter aortic valve replacement (TAVR).. Elevated levels of natriuretic peptides are associated with adverse outcomes across a wide spectrum of cardiovascular diseases. However, cutoff values differ according to age, gender, and body weight.. 244 TAVR patients with preprocedural NT-proBNP levels were analyzed, and the predictive value of NT-proBNP-ratio (measured NT-proBNP/maximal normal NT-proBNP values specific for age and gender) on all-cause-mortality was assessed in a multivariate model.. Median NT-proBNP-ratio was 4.2 [IQR 1.8-9.7]. All-cause mortality at 30 days was 3.4% in patients with less than median NT-proBNP-ratio, and 14.0% in patients with more than median NT-proBNP-ratio (P=0.02). All-cause mortality at 1 year was 8.5% in patients with less than median NT-proBNP-ratio, and 32.1% in those with more than median NT-proBNP-ratio (P=0.001). Cumulative survival declined with increasing quartiles of NT-proBNP-ratio (log rank P=0.001). All patients with a NT-proBNP-ratio below 1.5 survived at 1-year follow-up. In ROC analysis, NT-proBNP-ratio significantly predicted 30-day (AUC=0.72; P=0.002) and 1-year all-cause mortality (AUC=0.72; P<0.001). By multivariate Cox regression analysis, NT-proBNP-ratio, chronic obstructive pulmonary disease, and serum creatinine were the only independent predictors of all-cause mortality.. Elevated NT-proBNP-ratio was associated with increased short- and long-term mortality after TAVR, and independently predicted all-cause mortality. NT-proBNP-ratio should be considered in the risk stratification of patients undergoing TAVR.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Area Under Curve; Biomarkers; Cardiac Catheterization; Cause of Death; Chi-Square Distribution; Female; Heart Valve Prosthesis Implantation; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; ROC Curve; Severity of Illness Index; Switzerland; Time Factors; Treatment Outcome; Up-Regulation

Physicians utilize different types of information to predict patient prognosis. For example: confronted with a new patient suffering from severe aortic stenosis (AS), the cardiologist considers not only the severity of the AS but also patient characteristics, medical history, and markers such as BNP. Intuitively, doctors adjust their prediction of prognosis over time, with the change in clinical status, aortic valve area and BNP at each outpatient clinic visit. With the help of novel statistical approaches to model outcomes, it is now possible to construct dynamic event prediction models, employing longitudinal data such as AVA and BNP, and mimicking the dynamic adjustment of prognosis as employed intuitively by cardiologists. We illustrate dynamic prediction of patient survival and freedom from intervention, using baseline patient characteristics and longitudinal BNP data that are becoming available over time, from a cohort of patients with severe aortic stenosis.. A 3-step approach was employed: (1) construction of a mixed-effects model to describe temporal BNP progression, (2) jointly modeling the mixed-effects model with time-to-event data (death and freedom from intervention), and (3) using the joint model to build subject-specific prediction risk models. The dataset used for this purpose includes 191 patients with severe aortic stenosis who were followed over a 3-year time period.. In the mixed-effects model BNP was significantly influenced by time, baseline patient age, gender, LV fractional ejection fraction and creatinine. Additionally, the joint model showed that an increasing BNP trend over time was found to be a significant predictor of death.. By jointly modeling longitudinal data with time-to-event outcomes it is possible to construct individualized dynamic event prediction models that renew over time with accumulating evidence. It provides a potentially valuable evidence-based tool for everyday use in medical practice.

Topics: Age Factors; Aged; Aortic Valve Stenosis; Biomarkers; Creatinine; Female; Humans; Male; Models, Statistical; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Sex Factors; Stroke Volume; Time Factors

In heart failure populations without aortic stenosis (AS), the prognostic utility of multiple biomarkers in addition to clinical factors has been demonstrated. We aimed to determine whether multiple biomarkers of cardiovascular stress are associated with mortality in patients with AS undergoing aortic valve replacement (AVR) independent of clinical factors.. From a prospective registry of patients with AS, 345 participants who were referred for and treated with AVR (transcatheter (n=183) or surgical (n=162)) were included. Eight biomarkers were measured on blood samples obtained prior to AVR: growth differentiation factor 15 (GDF15), soluble ST2 (sST2), amino-terminal pro-B-type natriuretic peptide (NTproBNP), galectin-3, high-sensitivity cardiac troponin T, myeloperoxidase, high-sensitivity C reactive protein and monocyte chemotactic protein-1. Biomarkers were evaluated based on median value (high vs low) in a Cox proportional hazards model for all-cause mortality and a parsimonious group of biomarkers selected. Mean follow-up was 1.9±1.2 years; 91 patients died.. Three biomarkers (GDF15, sST2 and NTproBNP) were retained in the model. One-year mortality was 5%, 12%, 18% and 33% for patients with 0 (n=79), 1 (n=96), 2 (n=87) and 3 (n=83) biomarkers elevated, respectively (p<0.001). After adjustment for the Society of Thoracic Surgeons (STS) risk score, a greater number of elevated biomarkers was associated with increased mortality (referent: 0 elevated): 1 elevated (HR 1.47, 95% CI 0.60 to 3.63, p=0.40), 2 elevated (HR 2.89, 95% CI 1.24 to 6.74, p=0.014) and 3 elevated (HR 4.59, 95% CI 1.97 to 10.71, p<0.001). Among patients at intermediate or high surgical risk (STS score ≥4), 1-year and 2-year mortality rates were 34% and 43% for patients with three biomarkers elevated versus 4% and 4% for patients with 0 biomarkers elevated. When added to the STS score, the number of biomarkers elevated provided a category-free net reclassification improvement of 64% at 1 year (p<0.001). The association between a greater number of elevated biomarkers and increased mortality after valve replacement was similar in the transcatheter and surgical AVR populations.. These findings demonstrate the potential utility of multiple biomarkers to aid in risk stratification of patients with AS. Further studies are needed to evaluate their utility in clinical decision-making in specific AS populations.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cardiac Catheterization; Female; Growth Differentiation Factor 15; Heart Valve Prosthesis Implantation; Humans; Interleukin-1 Receptor-Like 1 Protein; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Receptors, Cell Surface; Registries; Risk Assessment; Risk Factors; Severity of Illness Index; Stress, Physiological; Time Factors; Treatment Outcome

Symptoms in the elderly patients with severe aortic stenosis (AS) and co-morbidities seem to lack in specificity. Therefore, objective parameters for increased left ventricular(LV) filling pressures are needed. The aim of this study was to investigate the correlation between the septal, lateral and average E/e' ratio and the value of the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP).. Two-hundred-fifty consecutive symptomatic patients (mean age 80 ± 8 years, 52% men) with severe AS underwent transthoracic echocardiography and NT-proBNP measurement.. In the overall population the septal E/e' (r = 0,459, r(2) = 0,21, P <0,0001), lateral E/e' (r = 0,322, r(2) = 0,10, P <0,0001), and the average E/e' (r = 0,432, r(2) = 0,18, P <0,0001) were all significantly correlated to NT-proBNP. After the exclusion of patients with confounders (more than mild aortic or mitral regurgitation, severe renal dysfunction, obesity or severe COPD) the septal E/e' (r = 0,584, r(2) = 0,34, P <0,0001), lateral E/e' (r = 0,377, r(2) = 0,14, P <0,0001), and the average E/e' (r = 0,487, r(2) = 0,24, P <0,0001) were all significantly better correlated to NT-proBNP. In obese patients no significant correlations were seen. Previous bypass surgery did not alter the correlations.. In elderly patients with severe symptomatic AS there is a significant correlation between the E/e' ratio and NT-proBNP, in particular after exclusion of confounders. The correlation was best for the septal E/e' ratio and was preserved in patients with a history of bypass surgery.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Echocardiography; Female; Geriatric Assessment; Humans; Image Interpretation, Computer-Assisted; Male; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Stroke Volume; Ventricular Dysfunction, Left

Patients with congenital aortic valve stenosis (AVS) can remain asymptomatic but may develop progressive and often underestimated exercise intolerance. The risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe AVS is clear, but optimal timing for moderate stenosis (modAS) is unknown. AVS often coexists with aortic regurgitation, which adds a volume overload to an already pressure-overloaded LV, adding an additional challenge to the estimation of disease severity. We investigated the possible value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) upon treadmill exercise challenge in children with asymptomatic modAS versus moderate regurgitation (modAR). The aim was to determine optimal timing of peak biochemical response. Blood samples were obtained at rest, and then at 20, 40 and 60 min after peak exercise comparing modAS and modAR to healthy controls. Exercise performance was equivalent in all groups, with no difference for biomarker levels at rest. The increase in NT-proBNP was significant in modAR at 40 min (99.2 ± 48.6 ng/L; p = 0.04) and 60 min into recovery (100.0 ± 53.7 ng/L; p = 0.01), but not in modAS. The increase in hs-cTnT was significant only at 60 min into recovery for modAS and modAR. NT-proBNP and hs-cTnT following exercise challenge are possible discriminant biomarkers of modAR from modAS and controls at 60 min into recovery despite comparable exercise performance. This offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.

Topics: Adolescent; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Child; Echocardiography; Exercise Test; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for morbidity and mortality after transcatheter aortic valve replacement (TAVR). We hypothesized that a portion of pulmonary dysfunction in patients with severe aortic stenosis may be of cardiac origin, and has potential to improve after TAVR.. A retrospective analysis was made of consecutive TAVR patients from April 2008 to October 2014. Of patients who had pulmonary function testing and serum B-type natriuretic peptide data available before and after TAVR, 58 were found to have COPD (26 mild, 14 moderate, and 18 severe). Baseline variables and operative outcomes were explored along with changes in pulmonary function. Multiple regression analyses were performed to adjust for preoperative left ventricular ejection fraction and glomerular filtration rate.. Comparison of pulmonary function testing before and after the procedure among all COPD categories showed a 10% improvement in forced vital capacity (95% confidence interval: 4% to 17%) and a 12% improvement in forced expiratory volume in 1 second (95% confidence interval: 6% to 19%). There was a 29% decrease in B-type natriuretic peptide after TAVR (95% confidence interval: -40% to -16%). An improvement of at least one COPD severity category was observed in 27% of patients with mild COPD, 64% of patients with moderate COPD, and 50% of patients with severe COPD. There was no 30-day mortality in any patient group.. In patients with severe aortic stenosis, TAVR is associated with a significant improvement of pulmonary function and B-type natriuretic peptide. After TAVR, the reduction in COPD severity was most evident in patients with moderate and severe pulmonary dysfunction.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vital Capacity

B-type natriuretic peptide (BNP) levels are elevated in patients with aortic stenosis (AS) and decrease acutely after replacement of the stenotic valve. The long-term prognostic value of BNP after transcatheter aortic valve implantation (TAVI) and the relative prognostic utility of single versus serial peri-interventional measurements of BNP and N-terminal prohormone BNP (NT-pro-BNP) are unknown. This study sought to determine the impact of BNP levels on long-term outcomes after TAVI and to compare the utility of BNP versus NT-pro-BNP measured before and after intervention. We analyzed 340 patients with severe AS and baseline pre-TAVI assessment of BNP. In 219 patients, BNP and NT-pro-BNP were measured serially before and after intervention. Clinical outcomes over 2 years were recorded. Patients with high baseline BNP (higher tertile ≥591 pg/ml) had increased risk of all-cause mortality (adjusted hazard ratio 3.16, 95% confidence interval 1.84 to 5.42; p <0.001) and cardiovascular death at 2 years (adjusted hazard ratio 3.37, 95% confidence interval 1.78 to 6.39; p <0.001). Outcomes were most unfavorable in patients with persistently high BNP before and after intervention. Comparing the 2 biomarkers, NT-pro-BNP levels measured after TAVI showed the highest prognostic discrimination for 2-year mortality (area under the curve 0.75; p <0.01). Baseline-to-discharge reduction, but not baseline levels of BNP, was related to New York Heart Association functional improvement. In conclusion, high preintervention BNP independently predicts 2-year outcomes after TAVI, particularly when elevated levels persist after the intervention. BNP and NT-pro-BNP and their serial periprocedural changes provide complementary prognostic information for symptomatic improvement and survival.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Severity of Illness Index; Time Factors; Transcatheter Aortic Valve Replacement

There are limited data on the effect of baseline B-type natriuretic peptide (BNP) on the outcome after transcatheter aortic valve implantation (TAVI). We investigated the influence of baseline BNP levels on the short-term and midterm clinical outcomes after TAVI. During a 3-year period, 780 patients with severe aortic stenosis underwent TAVI at our institute and had baseline BNP levels. We compared the high, mid, and low tertiles of BNP levels. TAVI end points, device success, and adverse events were considered according to the Valve Academic Research Consortium 2 definitions. Device success was significantly lower for patients with high BNP (98.1% vs 96.2% vs 91.9% for the low, mid, and high BNP tertiles, respectively; p = 0.003). All-cause mortality up to 30 days was 1.2% (3 of 260) versus 2.3% (6 of 260) versus 5% (13 of 260), respectively (p = 0.03). Six-month mortality rate was 4.1% (10 of 241) for the low BNP tertile, 5% (12 of 239) for the mid BNP tertile, and 17.1% (40 of 234) for the high BNP tertile (p <0.001). In the multivariate model, high tertile of baseline BNP was found to be significantly associated with all-cause mortality (hazard ratio 3.3, 95% confidence interval 1.64 to 6.48; p = 0.001). In conclusion, elevated BNP levels are associated with increased short-term and midterm mortality after TAVI. We recommend measurement of baseline BNP as part of risk stratification models for TAVI.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; California; Echocardiography, Transesophageal; Female; Humans; Imaging, Three-Dimensional; Male; Multidetector Computed Tomography; Natriuretic Peptide, Brain; Preoperative Period; Retrospective Studies; Survival Rate; Transcatheter Aortic Valve Replacement; Treatment Outcome

Patients with severe aortic stenosis (AS), high mean gradient (HMG), and preserved left ventricular ejection fraction (LVEF) may present with paradoxical "low flow" (LF).. The aim of the study was to assess the potential effect of cardiac collagen metabolism on the HMG/LF phenomenon in patients with severe AS and to determine a clinical and echocardiographic pattern of these patients.. We assessed a clinical status of 89 patients, aged over 64 years, with severe AS, HMG, and preserved LVEF (≥50%). Cardiac structure and function as well as systemic arterial hemodynamics were assessed with echocardiography, conventional Doppler, and tissue Doppler imaging. Moreover, plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), procollagen III N-terminal propeptide (PIIINP), carboxyterminal telopeptide of collagen type I, matrix metallopeptidase 9, and inhibitor of matrix metalloproteinase type 1 were evaluated. We analyzed 2 groups of patients: with normal flow (stroke volume index [SVI], ≥35 ml/m²; n = 70) and with LF (SVI, <35 ml/m²; n = 19).. Patients with LF were older, had a larger left atrium and left atrial volume index, smaller aortic valve area, lower energy loss index, stroke work, mitral flow E velocity, mitral annular E' and S' velocities and systemic arterial compliance, higher relative left ventricular wall thickness, E/E', systemic arterial resistance and valvulo-arterial impedance. We observed a correlation between SVI and NT-proBNP, PIIINP, and selected parameters of cardiac structure and function.. In patients with severe AS, HMG and preserved LVEF, the LF is related to a more severe obstruction, altered aortic hemodynamics, cardiac dysfunction, and higher blood levels of NT-proBNP. An inverse association between PIIINP and SVI may indicate enhanced tissue fibrosis as an underlying pathology.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Collagen; Echocardiography; Female; Humans; Male; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography, Stress; Exercise Tolerance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Little is known about the usefulness of evaluating cardiac neurohormones in patients undergoing transcatheter aortic valve implantation (TAVI). The objectives of this study were to evaluate the baseline values and serial changes of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) after TAVI, its related factors, and prognostic value. A total of 333 consecutive patients were included, and baseline, procedural, and follow-up (median 20 months, interquartile range 9 to 36) data were prospectively collected. Systematic NT-proBNP measurements were performed at baseline, hospital discharge, 1, 6, and 12 months, and yearly thereafter. Baseline NT-proBNP values were elevated in 86% of the patients (median 1,692 pg/ml); lower left ventricular ejection fraction and stroke volume index, greater left ventricular mass, and renal dysfunction were associated with greater baseline values (p <0.01 for all). Higher NT-proBNP levels were independently associated with increased long-term overall and cardiovascular mortalities (p <0.001 for both), with a baseline cut-off level of ∼2,000 pg/ml best predicting worse outcomes (p <0.001). At 6- to 12-month follow-up, NT-proBNP levels had decreased (p <0.001) by 23% and remained stable up to 4-year follow-up. In 39% of the patients, however, there was a lack of NT-proBNP improvement, mainly related to preprocedural chronic atrial fibrillation, lower mean transaortic gradient, and moderate-to-severe mitral regurgitation (p <0.01 for all). In conclusion, most patients undergoing TAVI presented high NT-proBNP levels, and a lack of improvement was observed in >1/3 of the patients after TAVI. Also, higher NT-proBNP levels predicted greater overall and cardiac mortalities at a median follow-up of 2 years. These findings support the implementation of NT-proBNP measurements for the clinical decision-making process and follow-up of patients undergoing TAVI.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Cardiac Catheterization; Diastole; Female; Heart Valve Prosthesis Implantation; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Protein Precursors; Stroke Volume; Ventricular Function, Left

This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation and survival after the diagnosis of aortic stenosis (AS).. In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting of BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series of patients have contributed to the uncertainty.. A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.. In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36 ± 19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p < 0.0001; hazard ratio [HR]: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (p < 0.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44 ± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 to 2.75), and 15 ± 2% with BNP ratio of ≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survival was confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 [95% CI: 1.57 to 3.56] for BNP clinical activation and 2.10 [95% CI: 1.32 to 3.36] for BNP ratio of 1 to 2, 2.25 [95% CI: 1.31 to 3.87] for BNP ratio of 2 to 3, 3.93 [95% CI: 2.40 to 6.43] for BNP ratio of ≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (p = 0.54) with BNP ratio of <2 (HR: 0.68; 95% CI: 0.52 to 0.89; p = 0.003) or BNP ratio of >2 (HR: 0.56; 95% CI: 0.47 to 0.66; p < 0.0001).. In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Prospective Studies; Survival Rate; Time Factors

Topics: Aortic Valve Stenosis; Female; Humans; Male; Natriuretic Peptide, Brain

Our objective was to assess the prognostic value of NT-proBNP in patients with asymptomatic moderate/severe aortic stenosis and to validate an adapted Monin score using natriuretic peptide levels in our setting.. Prospective study of 237 patients with degenerative asymptomatic moderate/severe aortic stenosis. NT-proBNP was determined in all patients, who were then followed up clinically. The adapted Monin score was defined as follows: (peak velocity [m/s]×2)+(logn NT-proBNP×1.5)(+1.5 if woman). A clinical event was defined as surgery, hospital admission due to angina, heart failure or syncope, or death.. A total of 51% were women, and the mean age was 74 years. Mean (SD) echocardiographic values were as follows: peak velocity 4.14 (0.87) m/s; mean gradient, 43.2 (16.0) mmHg; aortic valve area, 0.87 (0.72) cm(2), and aortic valve area index, 0.49 (0.14) cm(2)/m(2). The median NT-pro-BNP value was 490.0 [198.0-1312.0] pg/mL. There were 153 events during follow-up (median 18 months). The optimum NT-proBNP cut-point was 515 pg/mL, giving event-free survival rates at 1 and 2 years of 93% and 57%, respectively, in patients with NT-proBNP <515 pg/mL compared with 50% and 31% in those with NT-proBNP >515 pg/mL. Patients were divided into quartiles based on the Monin score. Event-free survival at 1 and 2 years was 87% and 79% in the first quartile, compared with 45% and 28% in the fourth quartile, respectively.. NT-proBNP determination provides prognostic information in patients with asymptomatic moderate/severe aortic stenosis. The adapted Monin score is useful in our setting and allows a more precise prognosis than does the use of NT-proBNP alone.

Topics: Aged; Aged, 80 and over; Algorithms; Aortic Valve Stenosis; Biomarkers; Female; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies

Elevated plasma B-type natriuretic peptide (BNP) is a predictor of outcome and helpful for risk stratification in aortic stenosis (AS). However, left ventricular (LV) diastolic dysfunction progresses with aging and may also influence plasma BNP levels in elderly patients. We hypothesized that plasma BNP levels may be influenced by age in severe AS, and that factors that affect the elevation of plasma BNP levels may be different between elderly and younger patients with AS.. We performed echocardiography in 341 patients with severe AS [aortic valve area (AVA)<1.0cm(2)] and classified them into two groups by age (elderly ≥75 years old, n=201; younger patients <75 years old, n=140). We used multivariate linear regression analysis to assess the factors that determine plasma BNP levels in both groups.. Age was found to be one of the independent determinants of plasma BNP levels in all patients (β=0.135, p=0.005). Although AVA was similar in the two groups, plasma BNP levels and E/e' were significantly higher in elderly than younger patients [133.0 (IQR, 73.3-329.7)pg/dl vs 92.8 (IQR, 40.6-171.8)pg/dl, p<0.01; 20±8 vs 16±6, p<0.01, respectively). In multivariate stepwise linear regression analysis, AVA index, LV ejection fraction, mass index, E/e', estimated systolic pulmonary artery pressure (eSPAS), and the presence of atrial fibrillation were independent determinants of plasma BNP levels in younger patients. In contrast, the independent determinants of plasma BNP levels in elderly patients were LV ejection fraction, mass index, E/e', eSPAS, the presence of atrial fibrillation, age, and hemoglobin levels, but not AVA index.. There may be differences in the factors that influence plasma BNP levels between elderly and younger patients with severe AS. In elderly patients, plasma BNP levels may be influenced more by these factors than AS severity compared with younger patients.

Topics: Age Factors; Aged; Aging; Aortic Valve Stenosis; Biomarkers; Echocardiography; Female; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Severity of Illness Index

Cardiac function and myocardial strain are affected by cardiac afterload, which is in part due to the stiffness of the aortic wall. In this study, we hypothesize that aortic pulse wave velocity (PWV) as a marker of aortic stiffness correlates with conventional clinical and biochemical markers of cardiac function and perioperative myocardial strain in aortic valve replacement (AVR).. Patients undergoing AVR for aortic stenosis between June 2010 and August 2012 were recruited for inclusion in this study. PWV, NYHA class and left ventricular (LV) function were assessed pre-operatively. PWV was analysed both as a continuous and dichotomous variable according to age-standardized reference values. B-type natriuretic peptide (BNP) was measured pre-operatively, and at 3 h and 18-24 h after cardiopulmonary bypass (CPB). NYHA class, leg edema, and LV function were recorded at follow-up (409 ± 159 days).. Fifty-six patients (16 females) with a mean age of 71 ± 8.4 years were included, with 50 (89%) patients completing follow-up. The NYHA class of PWV-norm patients was significantly lower than PWV-high patients both pre- and post-operatively. Multiple logistic regression also highlighted PWV-cut off as an independent predictor of NYHA class pre- and post-operatively (OR 8.3, 95% CI [2.27,33.33] and OR 14.44, 95% CI [1.49,139.31] respectively). No significant relationship was observed between PWV and either LV function or plasma BNP.. In patients undergoing AVR for aortic stenosis, PWV is independently related to pre- and post-operative NYHA class but not to LV function or BNP. These findings provisionally support the use of perioperative PWV as a non-invasive marker of clinical functional status, which when used in conjunction with biomarkers of myocardial strain such as BNP, may provide a holistic functional assessment of patients undergoing aortic valve surgery. However, in order for PWV assessment to be translated into clinical practice and utilised as more than simply a research tool, further validation is required in the form of larger prospective studies specifically designed to assess the relationship between PWV and these functional clinical outcomes.

Topics: Aged; Aged, 80 and over; Aorta, Thoracic; Aortic Valve; Aortic Valve Stenosis; Blood Pressure; Echocardiography; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Preoperative Period; Prognosis; Pulse Wave Analysis; Retrospective Studies; Vascular Stiffness; Ventricular Function, Left

B-type natriuretic peptide (BNP) level may be a useful prognostic marker for the management of asymptomatic patients with aortic stenosis (AS). The aim of this study was to identify the echocardiographic determinants of BNP changes during follow-up in AS. We studied 61 asymptomatic patients with greater than moderate AS and preserved left ventricular (LV) ejection fraction who underwent rest and exercise Doppler echocardiography with concomitant BNP level measurement at baseline. BNP measurement was repeated after inclusion every 6 months. Patients were divided into 2 groups according to the median of BNP changes during follow-up. According to parameters at rest, patients in the high BNP changes group had significantly higher E/e' ratio. Statistically significant correlations were found between BNP changes and E/e' ratio and indexed left atrial area. According to exercise parameters, patients in the high BNP changes group had significantly lower exercise-induced increase in LV ejection fraction. Statistically significant correlations were found between BNP changes and exercise-induced changes in LV ejection fraction. After adjustment for age, mean aortic pressure gradient, and BNP level at baseline, multivariate analysis identified indexed left atrial area, E/e' at rest, and exercise-induced increase in ejection fraction as independent determinants of BNP changes during follow-up. In conclusion, this study shows that, in asymptomatic patients with preserved LV function and moderate AS, serial BNP measurements may widely vary. Subclinical LV diastolic and systolic dysfunctions are frequently present in patients with higher serial BNP changes.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Time Factors; Ventricular Function, Left

Exercise-stress echocardiography is useful in management and risk stratification of patients with asymptomatic aortic stenosis (AS). Resting B-type natriuretic peptide (BNP) level is associated with increased risk of adverse events. The incremental prognostic value of BNP response during exercise is unknown. Objective The purpose of this study was to assess the usefulness of plasma level of BNP during exercise to predict occurrence of events in asymptomatic patients with severe AS.. Resting and exercise-stress echocardiographic data and plasma BNP levels were prospectively collected in 211 asymptomatic AS patients in whom 157 had severe AS with preserved LVEF in two centres. The study end-point was the occurrence of death or aortic valve replacement.. Plasma BNP level increased from rest to exercise (p<0.0001). During a mean follow-up of 1.5 ±1.2 years, 87 patients with severe AS reached the predefined end-point. Higher peak-exercise BNP level was associated with higher occurrence of adverse events (p<0.0001). In multivariate analysis, second and third tertiles of peak-exercise BNP (T2: HR=2.9; p=0.002 and T3: HR=5.3; p<0.0001, respectively) were powerful predictors of events compared with the first tertile. Further adjustment for resting BNP provided comparable results (T2: HR=2.8; p=0.003 and T3: HR=5.0; p<0.0001). This relationship persisted in both subsets of patients with low or high resting BNP.. This study reports that peak-exercise BNP level provides significant incremental prognostic value beyond what is achieved by demographic and echocardiographic data, as well as resting BNP level.

Topics: Aged; Aortic Valve Stenosis; Asymptomatic Diseases; Exercise Test; Female; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Severity of Illness Index

Fibulin-1, a circulating extracellular matrix glycoprotein, has been associated with arterial disease and elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in diabetes. Soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation, has been associated with subclinical atherosclerosis. Therefore, we aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS).. In 374 patients with mild to moderate AS, we investigated the relationship of fibulin-1 with NT-proBNP, levels of suPAR and the degree of AS at baseline and after one and four years of treatment with Simvastatin 40 mg and Ezetimibe 10 mg or placebo.. During treatment, fibulin-1 became more closely associated with NT-proBNP (βyear0 = 0.10, p = 0.08, βyear1 = 0.16, p = 0.005, βyear4 = 0.22, p<0.001) and suPAR (βyear0 = 0.05, p = 0.34, βyear1 = 0.16, p = 0.006, βyear4 = 0.13, p = 0.03) at the expense of the association to aortic valve area index (AVAI) (βyear0 = -0.14, p = 0.005, βyear1 = -0.08, p = 0.11, βyear4 = -0.06, p = 0.22) independently of age, gender, creatinine, and serum aspartate aminotransferase (Adj.Ryear02 = 0.19, Adj.Ryear12 = 0.22, Adj.Ryear42 = 0.27). Fibulin-1 was unrelated to aortic regurgitation, left ventricular mass, and ejection fraction. In patients with baseline AVAI<0.58 cm2/m2 (median value), fibulin-1 was more closely associated to NT-proBNP (βyear0 = 0.25, βyear1 = 0.21, βyear4 = 0.22, all p<0.01), and suPAR (βyear0 = 0.09, p = 0.26, βyear1 = 0.23, βyear4 = 0.21, both p<0.01) independently of age, gender, AST and treatment allocation.. Increased levels of fibulin-1 were independently associated with higher levels of suPAR and NT-proBNP especially in patients with lower AVAI, suggesting that fibulin-1 may be an early marker of AS as well as cardiac fibrosis secondarily to elevated left ventricular hemodynamic load.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Calcium-Binding Proteins; Echocardiography; Extracellular Matrix; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Receptors, Urokinase Plasminogen Activator

Topics: Aortic Valve Stenosis; Asymptomatic Diseases; Exercise Test; Female; Humans; Male; Natriuretic Peptide, Brain

The aim of this prospective study was to determine the impact of plasma B-type natriuretic peptide (BNP) on long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI).. TAVI was performed either transfemorally or transaxillary using either the CoreValve prosthesis or Edwards SAPIEN prosthesis in 226 patients with symptomatic severe aortic valve stenosis and at high surgical risk. The examinations included measurements of plasma BNP and echocardiography before and at 30 days after TAVI. The primary study end-point was death from any cause after TAVI; the secondary end-point was defined as cardiovascular death.. During a mean follow up of 728 ± 549 days, 72 patients died; 52 deaths were cardiovascular-related. Those patients who died had higher preprocedural plasma BNP levels compared to those who survived (1,305 ± 1,238 pg/ml versus 716 ± 954 pg/ml; p < 0.001). Plasma BNP was the strongest independent predictor of all-cause mortality (BNP > 475 pg/ml, hazard risk [HR] 3.049; 95% confidence interval [CI] 1.804-5.151; p < 0.001) and cardiovascular mortality (BNP > 475 pg/ml, HR 3.479; 95% CI 1.817-6.662; p < 0.001). In surviving patients, plasma BNP levels were decreased by 30 days after TAVI (pre-TAVI 874 ± 1,122 pg/ml; post TAVI 471 ± 569 pg/ml; p < 0.001). A plasma BNP level > 328 pg/ml at 30 days postoperatively was also associated with all-cause mortality (HR 8.125; 95% CI 3.097-21.318; p < 0.001).. In patients undergoing TAVI, plasma BNP is the strongest independent predictor of all-cause mortality and cardiovascular mortality. Plasma BNP levels at 30 days after TAVI may provide prognostic information that should, potentially, lead to a more intensive therapy of these patients.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Cause of Death; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Transcatheter Aortic Valve Replacement

It was the aim of this study to assess the pathophysiological, prognostic role of aortic regurgitation (AR) in the 'mixed pictures' of degenerative aortic valve stenoinsufficiency (ASI) by a multimarker clinical approach.. We enrolled 112 consecutive surgical. 19 with pure valve stenosis (PAS), 39 with mild regurgitation, 29 with severe regurgitation, and 25 controls with annulo-ectatic AR. All underwent complete echocardiography, carotid ultrasound and aortic/coronary multislice computed tomography calcium score evaluation. We determined tissue semiquantitative osteopontin, metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and circulating brain natriuretic peptide. We evaluated major adverse cardiac events and cardiovascular early, long-term mortality after bioprosthetic valve implantation.. Tissue calcification, carotid and coronary atherosclerotic disease were prevalent in PAS versus ASI and AR patients. The multislice computed tomography calcium score (Agatston) was comparable between PAS and ASI (PAS 3,507.3 + 2,442.6; mild AR 4,270.7 + 2,213.5; severe AR 3,568.5 + 1,823.4), but much lower in AR (1,247.8 + 2,708.6). In ASI, a plasma/tissue 'profibrotic' MMP/TIMP balance prevailed, with circulating and echocardiographic indices of myocardial dysfunction. Percentages of major adverse cardiac events and early, long-term mortality were higher in ASI.. In ASI, different, still unknown, genetic and dysplastic factors could work synergically with cardiovascular risk factors, determining a much more adverse myocardial and valve remodeling, resulting in worse clinical outcome.

Topics: Aged; Aortic Valve Insufficiency; Aortic Valve Stenosis; Atherosclerosis; Biomarkers; Bioprosthesis; Carotid Stenosis; Case-Control Studies; Female; Heart Valve Prosthesis Implantation; Humans; Male; Metalloproteases; Natriuretic Peptide, Brain; Osteopontin; Prognosis; Prospective Studies; Tissue Inhibitor of Metalloproteinases; Vascular Calcification

NT-proBNP has been shown to be a reliable biochemical marker for left ventricular wall stress. The relationship between NT-proBNP and coronary flow reserve (CFR) was evaluated in patients with significant asymptomatic aortic stenosis (AS).. A total of 74 patients with moderate or severe AS, mean age 66.68 ± 10.02 years (56.75% males), were enrolled in this prospective study. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter). They had all undergone standard transthoracic Doppler-echo study and adenosine stress transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP measurement.. The median NT-proBNP value was significantly increased (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was significantly higher in the group with CFR ≤2.5 (median: 549.0 pg/ml; IQR: 311.5-1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452; p = 0.012). NT-proBNP showed significant negative correlation with CFR (ρ = -0.377, p = 0.001). There was also significant correlation between NT-proBNP and E/E´, S´ and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was determined as the best cut-off value for the diagnosis of CFR ≤2.5 (area under the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity were 74 and 64%, respectively.. Elevated NT-proBNP can indicate patients with impaired CFR in asymptomatic moderate or severe AS patients with preserved ejection fraction and nonobstructive coronary arteries.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Diagnostic Techniques, Cardiovascular; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Regional Blood Flow; Young Adult

Few data are available on diastolic function in patients with aortic stenosis (AOS) with indication of surgical treatment. A potential correlation between biomarkers and diastolic function has not been established.. The aim of our study was to evaluate diastolic function in patients with AOS waiting for aortic valve replacement (AVR) echocardiographically, and to verify its correlation with serum brain natriuretic peptide (NT-proBNP).. Thirty-one AOS patients (11 male), 21 to 81 years old (mean age, 61±15 years old) were studied before and after AVR. Diastolic function was assessed with Doppler methods: transvalvar mitral flow, tissue Doppler imaging (TDI) and pulmonary venous Doppler (PVD), correlating with serum brain natriuretic peptide (NT-proBNP) before and 6 months after AVR.. Comparing pre to post-operative period, we observed an increase of the left atrial ejection fraction and isovolumetric relaxation time (IRT), and the decrease of the mitral velocity to early diastolic velocity of the mitral annulus ratio (E/E'), the difference between the pulmonary A wave duration and mitral A duration, left atrial systolic volume, left atrial systolic volume index, left ventricular diastolic diameter, left ventricular systolic diameter, end diastolic volume (LVEDV), left ventricular mass index, left ventricular volume and mass index ratio. The values of NT-proBNP were positively correlated to diastolic dysfunction, both before and after surgery.. AOS patients' ventricular diastolic function improved after AVR. The biomarker NT-proBNP might be a useful biomarker of diastolic function in these patients, before and after AVR. NT-proBNP values show a positive correlation with echocardiographic variables that determine diastolic dysfunction, and is a good marker for the characterization of this dysfunction in AOS patients.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Aortic Valve Stenosis; Biomarkers; Echocardiography, Doppler; Female; Heart Valve Prosthesis Implantation; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Preoperative Period; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling; Young Adult

The aim of this study was to evaluate predictors of recovery after balloon aortic valvuloplasty (BAV) among patients with aortic stenosis and depressed left ventricular ejection fraction (LVEF). Predictors for recovery after BAV are not clearly defined. B-type natriuretic peptide (BNP) predicts outcome after surgical and transcatheter aortic valve replacement.. Among 151 consecutive patients treated in our institution by BAV, a total of 59 with poor LVEF underwent an echocardiography at 1 month. In these 59 patients, LVEF significantly improved in 22 patients (group 1) from 27 ± 5% to 45 ± 6% (P<.0001) and remained unchanged in 37 patients (group 2) from 29 ± 8% to 30 ± 11% (P=NS). BNP plasma levels at 24 hours only decreased in group 1 from 2170 ± 967 pg/mL to 1208 ± 662 pg/mL (P=.001). By multivariate analysis, BNP reduction >300 pg/mL was the strongest independent predictor of LVEF improvement at 30 days (hazard ratio, 5.459; 95% confidence interval, 1.580-18.860; P=.007). Kaplan-Meier analysis showed that 1-year survival after BAV was significantly higher in patients of group 1 than in group 2 (95 ± 4% vs 51 ± 8%, respectively; P=.02).. BAV in patients with poor left ventricular function resulted in LVEF improvement at 30 days in 37% of cases, which was detected by a reduction of BNP levels already seen at 24 hours. Survival at 1 year was significantly higher in patients with such an improved LVEF after BAV.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Balloon Valvuloplasty; Biomarkers; Comorbidity; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Recovery of Function; Retrospective Studies; Stroke Volume; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

OBJECTIVES Left ventricular (LV) diastolic dysfunction after aortic valve replacement (AVR) carries a substantial risk of development of heart failure and reduced survival. In addition to echocardiography, B-type natriuretic peptide (BNP) provides a powerful incremental assessment of diastolic function. This study evaluates BNP as a marker of LV diastolic dysfunction in a cohort of patients with preserved LV ejection fraction who underwent AVR for pure aortic stenosis and the relationship between BNP values and the grade of LV diastolic dysfunction. METHODS A total of 113 patients were included in the study. Echocardiographic evaluation was performed preoperatively, 5 days postoperatively and at 12-month follow-up, to assess LV dimensional and functional parameters. Diastolic function was labelled as normal, mild, moderate or severe dysfunction. Concomitantly, BNP levels were evaluated. RESULTS Mild to severe diastolic dysfunction occurred preoperatively in all patients. At 12-month follow-up, 65 (62.5%) patients had mild and 25 (24.1%) moderate to severe diastolic dysfunction. BNP values, categorized for quartile distribution, correlated with diastolic dysfunction grade (P<0.001 for each comparison). At receiver operating characteristic analysis, the BNP level of 120 pg/ml was 91% sensitive and 85% specific for diastolic disease, while 300 pg/ml was 80% sensitive and 91% specific for moderate or severe diastolic dysfunction. Twelve months after AVR, BNP values were strongly correlated with the significant echocardiographic parameters suggestive of diastolic dysfunction (P≤0.006 in all cases). CONCLUSIONS The BNP level following AVR is related to diastolic disease severity and may complement echocardiographic evaluation when symptoms are unclear and LV function is difficult to interpret.

Topics: Aged; Aortic Valve Stenosis; Asymptomatic Diseases; Biomarkers; Chi-Square Distribution; Diastole; Echocardiography, Doppler, Color; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Severity of Illness Index; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Brain natriuretic peptide (BNP) is a marker of systolic and diastolic dysfunction and a strong predictor of mortality in heart failure patients. The present study aimed to assess the relationship of BNP with aortic stenosis (AS) severity and prognosis. The cohort comprised 289 high-risk patients with severe AS who were referred for transcatheter aortic valve implantation. Patients were divided into tertiles based on BNP level: I (n = 96); II (n = 95), and III (n = 98). Group III patients were more symptomatic, had higher Society of Thoracic Surgeons and EuroSCORE scores, and had a greater prevalence of renal failure, atrial fibrillation, and previous myocardial infarction; lower ejection fraction and cardiac output; and higher pulmonary pressure and left ventricular end diastolic pressure. The degree of AS did not differ among the 3 groups. Stepwise forward multiple regression analysis identifies ejection fraction and pulmonary artery systolic pressure as independent correlates with plasma BNP. Mortality rates during a median follow-up of 319 days (range 110 to 655) were significantly lower in Group I compared with Groups II and III, p <0.001. After multivariable adjustment, the strongest correlates for mortality were renal failure (hazard ratio 1.44, p = 0.05) and medical/balloon aortic valvuloplasty (HR 2.2, p <0.001). Mean BNP decreased immediately after balloon aortic valvuloplasty from 1,595 ± 1,229 to 1,252 ± 1,076, p = 0.001 yet increased to 1,609 ± 1,264, p = 0.9 at 1 to 12 months. After surgical aortic valve replacement, there was a nonsignificant, immediate decrease in BNP level from 928 ± 1,221 to 896 ± 1,217, p = 0.77, continuing up to 12 months 533 ± 213, p = 0.08. After transcatheter aortic valve implantation, there was no significant decrease in BNP immediately after the procedure; however, at 1-year follow-up, the mean BNP level decreased significantly from 568 ± 582 to 301 ± 266 pg/dl, p = 0.03. In conclusion, a high BNP level in high-risk patients with severe AS is not an independent marker for higher mortality. BNP level does not appear to be significantly associated with the degree of AS severity but does reflect heart failure status.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cardiac Catheterization; Chi-Square Distribution; Comorbidity; Echocardiography; Female; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Male; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Prognosis; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Severity of Illness Index; Survival Rate

Aortic valve sclerosis (AVSc), the early asymptomatic stage of calcific aortic valve disease (CAVD), is characterized by a progressive thickening of the aortic cusps without obstruction of the left ventricular outflow. In spite of its high prevalence, there are no molecular markers to characterize the early stages of CAVD before it progresses to a severe, symptomatic stage of aortic valve stenosis (AVS). The study aim was to identify any correlation between circulating biomarkers and transesophageal echocardiography (TEE) evaluation.. A total of 330 patients with various degrees of CAVD was enrolled into the study. Blood was collected from each patient prior to surgery, and analyzed using ELISA kits following the manufacturers' instructions.. Significantly higher plasma osteopontin (OPN) levels were observed in AVSc patients (72.7 +/- 1.8 ng/ml; p < 0.001) and AVS patients (64.3 +/- 5.1 ng/ml; p < 0.001) when compared to controls (30.3 +/- 1.8 ng/ml). Parathyroid hormone (PTH) levels in AVSc and AVS patients (164.1 +/- 16.5 and 134.3 +/- 14.6 pg/ml; p < 0.001 and p = 0.04, respectively) were also significantly higher than in controls (61.8 +/- 4.92 pg/ml). Upon further analysis, plasma levels of OPN (p < 0.001) and PTH (p < 0.001) were found to be significantly higher in asymptomatic AVSc patients, even before calcium deposition was detected on TEE evaluation. Fetuin-A levels were lower at all stages of CAVD when compared to controls (p < 0.001 and p < or = 0.05, respectively), but were comparable among the patient groups. NT-proBNP levels were significantly higher in AVS patients than in controls (p < or = 0.01).. Serum levels of OPN, PTH, and fetuin-A showed a significant association with different stages of CAVD, with variations in their levels occurring before calcium nodules are visualized during TEE evaluation. The study results may help not only to provide a better understanding of the progression of CAVD but also to develop new tools that can be used to stage these patients.

Topics: Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Aortic Valve; Aortic Valve Stenosis; Arginine; Biomarkers; Calcinosis; Case-Control Studies; Echocardiography, Transesophageal; Female; Humans; Male; Natriuretic Peptide, Brain; Osteopontin; Parathyroid Hormone; Peptide Fragments; Sclerosis; Severity of Illness Index

We report a case of successful 2-stage percutaneous closure of severe paravalvular leak (PVL) in a patient with stentless aortic bioprosthesis. Threat of pliable prosthesis compression and long course of PVL posed main considerations. Accordingly, Amplatzer vascular plug (AVP) 2 was chosen as occluder. It was delivered transfemorally under fluoroscopy and transesophageal echocardiography guidance. No prosthesis distortion was provoked at the expense of moderate residual leak. Its symptoms after 3 months spurred another AVP 2 implantation, which lead to PVL closure with no effect on valve area. Marked reduction of left ventricle cavity size and NT-proBNP plasma concentration was promptly noted and remains stable in 12-month follow-up.

Topics: Aortic Valve Insufficiency; Aortic Valve Stenosis; Aortography; Biomarkers; Bioprosthesis; Cardiac Catheterization; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prosthesis Design; Prosthesis Failure; Radiography, Interventional; Time Factors; Treatment Outcome

Copeptin is a new biomarker of cardiovascular diseases. Its diagnostic value in degenerative aortic valve stenosis (AS) with preserved left ventricle systolic function is unknown. We aimed to assess the association of serum copeptin levels with AS severity and coexistence of coronary artery disease (CAD). Sixty-four patients with AS and preserved left ventricle systolic function including 40 with severe degenerative AS (group sAS, effective orifice area EOA = 0.67 cm(2)) and 24 with moderate degenerative AS (group mAS, EOA = 1.40 cm(2)) were enrolled into the study. Twenty-three patients without AS and heart failure, matched for age, sex, and CAD occurrence served as the control group (group C). Serum levels of copeptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using enzyme-linked immunosorbent assay. The mean serum copeptin concentrations were significantly higher in patients with AS: sAS (405 pg/ml) and mAS (351 pg/ml; sAS vs mAS P < 0.05), compared with group C (302 pg/ml, P < 0.05). Serum copeptin levels correlated inversely with EOA (r = -0.55; P < 0.001) in AS patients. There was no correlation between copeptin and NT-proBNP or association with the coexisting CAD. Receiver-operating characteristics analysis showed that copeptin was a good marker of severe/moderate AS (sensitivity 71 %; specificity 87 %), with the optimized cut-off value of 354 pg/ml. Serum copeptin concentration constitutes a novel biomarker of degenerative AS. Coexisting CAD does not interfere with copeptin level.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Case-Control Studies; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Glycopeptides; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; ROC Curve; Severity of Illness Index; Systole; Up-Regulation; Ventricular Function, Left

To evaluate the prevalence of cardiac troponin I (cTnI) and autoantibodies to cTn in children with congenital heart defects with volume or pressure overload fulfilling the criteria for treatment, and in healthy children.. The study groups comprised 78 children with volume overload caused by an atrial septal defect or a patent ductus arteriosus, and 60 children with pressure overload caused by coarctation of the aorta or stenosis of the aortic or the pulmonary valve, and 74 healthy controls. Serum levels of natriuretic peptides, cTnI, and autoantibodies to cTn were analyzed at baseline, prior to treatment and in 64 patients 6 months after treatment.. At baseline, one child with volume overload, 12 children with pressure overload, and one healthy control had positive cTnI. Further analysis of the pressure overload subgroup revealed that the children with positive cTnI were younger than those with negative cTnI, and had higher levels of natriuretic peptides. The pressure gradient at the coarctation site or stenotic valve was higher in those with positive TnI. Six months after treatment, 63 of 64 children examined were cTnI negative.. The cTnI release is more frequently associated with pressure than volume overload which resolves after treatment in most children.

Topics: Adolescent; Aortic Coarctation; Aortic Valve Stenosis; Atrial Natriuretic Factor; Autoantibodies; Biomarkers; Case-Control Studies; Child; Child, Preschool; Ductus Arteriosus, Patent; Female; Heart Defects, Congenital; Heart Failure; Heart Septal Defects, Atrial; Hemodynamics; Humans; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Pulmonary Valve Stenosis; Time Factors; Troponin I; Young Adult

Decision making in patients with low flow-low gradient aortic stenosis mainly depends on the actual stenosis severity and left ventricular function, which is of prognostic importance. We used 2-dimensional strain parameters measured by speckle tracking at rest and during dobutamine stress echocardiography to document the extent of myocardial impairment, its relationship with hemodynamic variables, and its prognostic value.. In 47 patients with low flow-low gradient aortic stenosis, global peak systolic longitudinal strain (PLS) and peak systolic longitudinal strain rate (PLSR) were analyzed. PLS and PLSR at rest and peak stress were -7.56±2.34% and -7.41±2.89% (P=NS) and -0.38±0.12 s(-1) and -0.53±0.18 s(-1) (P<0.001), respectively. PLS and PLSR inversely correlated with left ventricular ejection fraction at rest (rs=-0.52; P<0.0001 and -0.38; P=0.008) and peak stress (rs=-0.39; P=0.007 and -0.45; P=0.002). The overall 2-year survival rate was 60%. Univariate predictors of survival were peak stress left ventricular ejection fraction (P=0.0026), peak stress PLS (P=0.0002), peak stress PLSR (P<0.0001), and N-terminal pro-B-type natriuretic peptide (P<0.0001). Three hierarchically nested multivariable Cox regression models were constructed-model 1: The Society of Thoracic Surgeons score as an indicator of clinical risk (area under the receiver operating characteristic=0.59); model 2: model 1+N-terminal pro-B-type natriuretic peptide and peak stress left ventricular ejection fraction (area under the receiver operating characteristic=0.83; incremental P<0.0001); model 3: model 2+peak stress PLSR (area under the receiver operating characteristic=0.89; incremental P=0.035).. In patients with low flow-low gradient aortic stenosis, 2-dimensional strain parameters are strong predictors of outcome. Peak stress PLSR may add incremental prognostic value beyond what is obtained from N-terminal pro-B-type natriuretic peptide and peak stress left ventricular ejection fraction. A larger study is needed to confirm these findings.

Topics: Adrenergic Agonists; Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Chi-Square Distribution; Dobutamine; Echocardiography, Doppler; Echocardiography, Stress; Female; Heart Ventricles; Hemodynamics; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Severity of Illness Index; Stress, Mechanical; Stroke Volume; Survival Rate; Time Factors; Ventricular Function, Left

To determine the prognostic value of pro B-type natriuretic peptide (pro-BNP) to predict mortality after transcatheter aortic valve implantation (TAVI). Logistic EuroSCORE (LES) overestimates observed mortality after TAVI. A new risk score specific to TAVI is needed to accurately assess mortality and outcome.. Eighty-five patients were included. Indications for TAVI were nonoperable or surgically high-risk patients (LES>20%). Pro-BNP was measured 24h before the procedure. Cox proportional hazards model was used to evaluate clinical factors. The predictive accuracy of these Cox models was determined by using time-dependent receiver operating characteristic (ROC) curves.. Pro-BNP levels (log-transformed) were significantly higher in non-survivors than in survivors at 30 days (3.36 ± 0.43 vs. 3.81 ± 0.43, p<0.004) and at the end of follow-up (3.34 ± 0.42 vs. 3.63 ± 0.48, p<0.011). Multivariate analysis revealed that only increased log pro-BNP levels were associated with higher mortality rate at short [hazard ratio (HR) (95% confidence intervals (CI)]=5.35 (1.74-16.5), p=0.003] and long-term follow-ups [HR=11 (CI: 1.51-81.3), p=0.018]. LES was not associated with increased mortality at either time point [HR=1.03 (CI: 0.95-1.10), p=0.483 and HR=1.03 (CI: 0.98-1.07), p=0.230, respectively]. At 30, 90, 180, and 365 days, the c-index was 0.72 for log pro-BNP and 0.63 for LES (p=0.044).. Pre-procedure log transform of plasma pro-BNP levels are an independent and strong predictor of short- and long-term outcomes after TAVI and are more discriminatory than LES.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cardiac Catheterization; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Time Factors; Treatment Outcome

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been found to correlate with the severity of aortic valve stenosis and to provide prognostic information in aortic stenosis patients undergoing surgical aortic valve replacement. There is a paucity of data describing the association between clinical outcomes after TAVI and NT-proBNP levels. We investigated the evolution and prognostic value of NT-proBNP levels after TAVI.. We prospectively collected data on the baseline characteristics, NT-proBNP levels (baseline, post-treatment and discharge) and adverse clinical outcomes of patients undergoing TAVI from 2007 to 2010. Using a univariable and multivariable Cox regression model, pre- and postimplantation NT-proBNP tertile levels were correlated to 30-day and 1-year mortality. A total of 373 patients underwent TAVI with either the Medtronic CoreValve or Edwards SAPIEN prosthesis. The cumulative 30-day and 1-year mortality was 7.3% and 18%, respectively. Rehospitalization for heart failure was observed in 0.8% at 30 days and 7.8% at 1 year. The tertile baseline NT-proBNP levels were identified as ≤1570 ng/L, 1571 to 4690 ng/L and ≥4691 ng/L. In the univariable analysis, baseline (HR, 1.01; 95% CI, 1.001-1.02; P=.02) and post-treatment NT-proBNP (HR 1.02; 95% CI, 1.002-1.04; P=.04) were predictors for 1-year mortality. In the multivariable analysis, however, only baseline NT-proBNP and atrial fibrillation were identified as predictors for the 1-year mortality (HR, 1.02; 95% CI, 1.01-1.05; P=.006 and HR, 3.4; 95% CI, 1.25-9.5; P=.017, respectively).. NT-proBNP and atrial fibrillation were predictors for 1-year mortality, offer independent prognostic information, and identify patients being at increased risk for mortality. Thus, NT-proBNP reveals more incremental value for patient selection and should be included in the risk stratification of patients undergoing TAVI.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Atrial Fibrillation; Balloon Valvuloplasty; Biomarkers; Female; Follow-Up Studies; Heart Failure; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors

Previous studies suggested an independent prognostic value of B-type natriuretic peptide (BNP) in aortic valve stenosis (AS) but were impeded by small sample sizes and inclusion of relatively selected young patients. We aimed to evaluate the relationship among N-terminal fragment of proBNP (Nt-proBNP), AS severity, symptoms and outcome in a large cohort of elderly patients with AS.. Observational cohort study, COhorte Française de Retrecissement Aortique du Sujet Agé (clinicalTrial.gov number-NCT00338676) and GENEtique du Retrecissement Aortique (clinicalTrial.gov number-NCT00647088).. Single-centre study.. Patients older than 70 years with at least mild AS.. None.. A comprehensive clinical, biological and echocardiographic evaluation was performed at study entry. Asymptomatic patients were prospectively followed on a 6-months basis and AS-related events (sudden death, congestive heart failure or new onset of AS-related symptoms) collected.. We prospectively enrolled 361 patients (79±6 years, 230 severe AS). Nt-proBNP increased with the grade of AS severity and the NYHA class (all p<0.0001) but there was an important overlap between grades/classes. Consequently, diagnostic value of Nt-proBNP for the diagnosis of severe symptomatic AS was only modest (area under the curve of the receiver operator characteristic analysis=0.73). At 2 years, 28 AS-related events occurred among 142 asymptomatic patients prospectively followed. Nt-proBNP was associated with outcome in univariate analysis (p=0.04) but not after adjustment for age, gender and AS severity (p=0.40).. The present study clearly highlights the limitations of Nt-proBNP for the evaluation and management of AS patients. Our results suggest that Nt-proBNP should be considered cautiously, at least as a single criterion, in the decision-making process of AS patients especially in the elderly population.

Topics: Age Factors; Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Chi-Square Distribution; Decision Support Techniques; Disease Progression; Disease-Free Survival; Echocardiography, Doppler; Female; Follow-Up Studies; France; Heart Failure; Humans; Kaplan-Meier Estimate; Linear Models; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Severity of Illness Index; Time Factors

Severe autonomic failure (SAF) refers to combined abnormalities in reflex and tonic autonomic function. SAF indicates increased risk of death in post-infarction and heart failure patients, but has not been studied in aortic stenosis (AS). Here, we investigated SAF in patients with AS and tested its correlation with hemodynamic and biochemical markers.. We prospectively enrolled 174 patients with moderate to severe AS in sinus rhythm (age 76 ± 9 years; mean aortic valve area 0.9 ± 0.3 cm(2)). Heart rate turbulence (as marker of autonomic reflex activity) and deceleration capacity (as marker of autonomic tonic activity) were calculated from 24-h Holter recordings. According to the previously published technology, SAF was considered present if both factors were abnormal.. 44 (25.3%) of the 174 patients had signs of SAF. Patients with SAF had lower left ventricular ejection fraction (LVEF: 48.1 vs. 54.8%; p = 0.002), lower mean aortic gradients (28 vs. 34 mmHg, p = 0.019), higher systolic pulmonary artery pressures (46.8 vs. 40.9 mmHg, p = 0.028), higher levels of brain natriuretic peptide (905 vs. 407 ng/l; p = 0.003) and higher levels of high sensitive troponin I (0.65 vs. 0.24 μg/l; p = 0.013). Impaired LVEF (≤50%) was the only independent factor associated with SAF, but only explained autonomic abnormalities in less than half of the patients.. In patients with moderate to severe AS prevalence of SAF is high. SAF correlates with hemodynamic and biochemical markers indicating increased risk. Future studies should evaluate the prognostic value of SAF in patients with AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Autonomic Nervous System; Autonomic Nervous System Diseases; Biomarkers; Blood Pressure; Chi-Square Distribution; Electrocardiography, Ambulatory; Female; Germany; Heart Rate; Hemodynamics; Humans; Logistic Models; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prevalence; Prospective Studies; Reflex; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Troponin T; Ventricular Function, Left

Aortic stenosis (AS) and atherosclerosis share similarities when it comes to risk factors and disease progression. Like in other heart diseases, we hypothesized that biomarkers like high-sensitive troponin T (hsTnT), N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) and high-sensitive C-reactive protein (hsCRP) could be useful in risk stratification.. A total of 136 patients (57% men, mean age 74 years), referred for evaluation of AS (valve area 0.62 cm(2), left ventricular ejection fraction 64%) were consecutively enrolled in the study. The relationship between hsTnT, hsCRP and NT-proBNP, different echocardiographic parameters of AS and cardiac function were investigated as well as their relation to all-cause mortality.. In contrast to hsCRP, hsTnT and NT-proBNP were individually correlated with prognosis. Regression analysis identified diabetes and the combination of hsTnT and NT-proBNP as significant predictors of all-cause mortality. When analyzing patients without surgery separately, only the combination of hsTnT and NT-proBNP were identified as a significant predictor of all-cause mortality in multivariable analysis.. The combination of NT-proBNP and hsTnT came out as the strongest predictor of outcome irrespective of surgical treatment or not and could be of particular interest in risk-stratification in AS-patients. The results should be confirmed in prospective studies both in symptomatic and asymptomatic patients.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; C-Reactive Protein; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Troponin T

Prominent features of myocardial remodeling in heart failure with preserved ejection fraction (HFPEF) are high cardiomyocyte resting tension (F(passive)) and cardiomyocyte hypertrophy. In experimental models, both reacted favorably to raised protein kinase G (PKG) activity. The present study assessed myocardial PKG activity, its downstream effects on cardiomyocyte F(passive) and cardiomyocyte diameter, and its upstream control by cyclic guanosine monophosphate (cGMP), nitrosative/oxidative stress, and brain natriuretic peptide (BNP). To discern altered control of myocardial remodeling by PKG, HFPEF was compared with aortic stenosis and HF with reduced EF (HFREF).. Patients with HFPEF (n=36), AS (n=67), and HFREF (n=43) were free of coronary artery disease. More HFPEF patients were obese (P<0.05) or had diabetes mellitus (P<0.05). Left ventricular myocardial biopsies were procured transvascularly in HFPEF and HFREF and perioperatively in aortic stenosis. F(passive) was measured in cardiomyocytes before and after PKG administration. Myocardial homogenates were used for assessment of PKG activity, cGMP concentration, proBNP-108 expression, and nitrotyrosine expression, a measure of nitrosative/oxidative stress. Additional quantitative immunohistochemical analysis was performed for PKG activity and nitrotyrosine expression. Lower PKG activity in HFPEF than in aortic stenosis (P<0.01) or HFREF (P<0.001) was associated with higher cardiomyocyte F(passive) (P<0.001) and related to lower cGMP concentration (P<0.001) and higher nitrosative/oxidative stress (P<0.05). Higher F(passive) in HFPEF was corrected by in vitro PKG administration.. Low myocardial PKG activity in HFPEF was associated with raised cardiomyocyte F(passive) and was related to increased myocardial nitrosative/oxidative stress. The latter was probably induced by the high prevalence in HFPEF of metabolic comorbidities. Correction of myocardial PKG activity could be a target for specific HFPEF treatment.

Topics: Aortic Valve Stenosis; Biopsy; Cohort Studies; Comorbidity; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Diabetes Mellitus; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Obesity; Oxidative Stress; Stroke Volume; Tyrosine

The natriuretic peptides, brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP), can be used as diagnostic and prognostic markers for aortic stenosis (AS). However, the association between BNP, NT-proBNP, and long-term clinical outcomes in patients with severe AS remains uncertain.. A total of 64 patients with severe AS was prospectively enrolled into the study, and underwent clinical and echocardiographic assessments at baseline. Blood samples were drawn for plasma BNP and NT-proBNP analyses. The primary outcome was death from any cause, through a six-year follow up period. Cox proportional hazards modeling was used to examine the association between natriuretic peptides and long-term mortality, adjusting for important clinical factors.. During a mean period of 1,520 +/- 681 days, 51 patients (80%) were submitted to aortic valve replacement, and 13 patients (20%) were medically managed without surgical interventions. Mortality rates were 13.7% in the surgical group and 62% in the medically managed group (p < 0.001). Patients with higher plasma BNP (> 135 pg/ml) and NT-proBNP (> 1,150 pg/ml) levels at baseline had a greater risk of long-term mortality (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1-9.1; HR 4.3, 95% CI 1.4-13.5, respectively). After adjusting for important covariates, both BNP and NT-proBNP remained independently associated with long-term mortality (HR 2.9, 95% CI 1.5-5.7; HR 1.8, 95% CI 1.1-3.1, respectively).. In patients with severe AS, plasma BNP and NT-proBNP levels were associated with long-term mortality. The use of these biomarkers to guide treatment might represent an interesting approach that deserves further evaluation.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Disease Management; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome and Process Assessment, Health Care; Peptide Fragments; Prognosis; Severity of Illness Index; Survival Rate; Survivors

Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction.. One hundred thirty-five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty-nine patients (66%) had severe AVS (aortic valve area <0.6 cm(2) /m(2) BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R(2) = 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R(2) = 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R(2) = 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003).. In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se. 

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Comorbidity; Coronary Angiography; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Wedge Pressure; Regression Analysis; Risk Factors; Stroke Volume

The diagnostic and prognostic value of plasma B-type natriuretic peptide (BNP) level in isolated aortic stenosis (AS) has not been fully understood.. BNP level was determined in 109 consecutive patients with isolated severe AS (68.1 ± 10.6 years; 53 men; transvalvular peak gradient, 87.2 ± 37.0 mm Hg; valve area index, 0.43 ± 0.14 cm(2)/m(2)) and 12 healthy volunteers in their stable state. They were followed up for 36 months.. BNP level increased with New York Heart Association (NYHA) class (75.2 ± 95.9 pg/mL, 135.0 ± 112.0 pg/mL, 450.6 ± 366.3 pg/mL, and 1478.9 ± 941.5 pg/mL for NYHA I, II, III, and IV, respectively). Left ventricular (LV) mass index had the best relationship with BNP (r = 0.73, P < .0001). Aortic valve replacement (AVR) was eventually performed in 95 patients (male = 44, age = 67.8 ± 9.3 years). Echocardiography was repeated early (n = 88, 13.2 ± 6.2 day) and late (n = 62, 32 ± 10 months) after AVR. Preoperative BNP level correlated with LV mass index early (r = 0.74, P < .0001) and late (r = 0.78, P < .0001) after AVR. Patients with higher BNP level had a tendency to show cardiac symptoms (NYHA > I) late after AVR (NYHA I vs. > I = 160.8 ± 197.9 pg/mL vs. 504.3 ± 567.3 pg/mL, P < .0001). Preoperative BNP level predicted the occurrence of perioperative complications (P < .0001). During follow-up of the 94 patients (44 ± 10 months after AVR), 10 were readmitted for major cardiac and cerebrovascular events, including 9 patients with congestive heart failure and 1 patient with ischemic stroke. An event-free survival rate was significantly higher in patients with BNP ≤ 312 pg/mL than in patients with BNP > 312 pg/mL (log rank, χ(2) = 10.21, P = .001). Multiple logistic regression analysis revealed that BNP > 312 pg/mL was an independent predictor of AVR complication (odds ratio 5.58; confidence interval, 1.82-20.16; P = .002). Furthermore, BNP was the strongest predictor of major adverse cardiac and cerebrovascular events within 36 months after AVR (odds ratio 8.80; confidence interval, 1.83-42.35; P = .006).. Plasma BNP level reflects the degree of heart failure, is associated with LV structure and function in severe AS, and is an independent predictor of complication and outcome after AVR. BNP level may be useful in risk stratification of patients with AS in conjunction with other clinical and echocardiographic parameters.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Echocardiography; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Severity of Illness Index; Time Factors; Young Adult

To examine the prognostic value of osteoprotegerin (OPG) levels in relation to all-cause mortality in patients with symptomatic severe aortic stenosis (AS).. We measured plasma OPG levels in 136 patients with symptomatic severe AS and investigated associations with transvalvular gradients, valve area, valve calcification (using ultrasonic backscatter analysis as an estimate) and measures of heart failure. Then, we assessed the prognostic value of elevated plasma OPG in determining all-cause mortality (n = 29) in these patients.. Elevated OPG was poorly correlated with the degree of AS but was associated with increased backscatter measurements and impaired cardiac function. Furthermore, OPG was associated with all-cause mortality in patients with symptomatic AS, even after adjustment for conventional risk markers. The strongest association was obtained by using a combination of high levels of both OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP), suggesting that these markers may reflect distinct pathways in the development and progression of AS.. The level of circulating OPG is significantly associated with all-cause mortality alone and in combination with NT-proBNP in patients with severe symptomatic AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Female; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Osteoprotegerin; Peptide Fragments; Predictive Value of Tests

Severe aortic stenosis (AS) with preserved systolic function may coexist with 'low flow' and a lower stroke volume (SV). As the mechanisms of this phenomenon are not fully understood, the study aim was to assess the cardiac and vascular mechanisms of 'low-flow' severe AS with a preserved left ventricular ejection fraction (LVEF).. Forty-four consecutive patients (mean age 69.7 +/- 7.6 years) with severe degenerative AS [mean effective orifice area (EOA) 0.7 +/- 0.3 cm2] and preserved LVEF (> 50%) were enrolled into the study, and allocated to two groups depending on their stroke volume index (SVI) (< 35 and > or = 35 ml/m2, respectively). The clinical data, N-terminal pro-brain natriuretic peptide (NT-proBNP) serum levels and ultrasound assessment of LV geometry and function [stroke work (SW), relative wall thickness (RWT)], AS severity, indices of systemic arterial hemodynamics [systemic arterial compliance (SAC), systemic vascular resistance (SVR)] and remodeling [flow-mediated dilatation (FMD), pulse wave velocity (PWV)], as well as valvuloarterial impedance (Z(va)) were analyzed for all study patients.. Twenty-four patients (56%; 13 females, 11 males) had low-flow LV output, and 20 (44%; four females, 16 males) had a normal LV output. The mean NT-proBNP serum levels were comparable between the study groups. An analysis of LV remodeling and function revealed a lower LV end-diastolic volume (LVEDV; 85.5 +/- 24.1 versus 160.4 +/- 60.9 ml, p = 0.001), LV end-systolic volume (LVESV; 40.3 +/- 18.5 versus 66.8 +/- 44.2 ml, p = 0.03), LV mass index (LVMI; 150.1 +/- 53.4 versus 183.7 +/- 57.5 g/m2, p = 0.07) and SW (95.6 +/- 23.7 versus 183.2 +/- 50.6 mmHg x ml, p < 0.0001) in the group with SVI < 35 ml/m2. The average RWT was higher in the group with SVI < 35 ml/m2 (48.7 +/- 14.8 versus 40.0 +/- 7.5, p = 0.04). The indices of systemic arterial hemodynamics were significantly different between the groups: the SAC was lower, and the SVR and Z(va) were higher, in patients with SVI < 35 ml/m2 while FMD values were significantly greater in patients with SVI < 35 ml/m2 (11.85 +/- 6.4 versus 7.29 +/- 6.3%, p = 0.035). However, the brachial artery diameter (BAd) was smaller in the latter group, and no differences were found in the FMD x BAd index values. The PWV values were comparable in both study groups.. The low-flow phenomenon in severe AS with preserved LVEF is related to smaller LV dimensions, LV concentric hypertrophy, and an increased systemic arterial afterload without differences in plasma NT-proBNP levels. 'Paradoxically' higher values of FMD observed in this population may be associated with a higher proportion of females and a smaller BAd.

Topics: Aged; Analysis of Variance; Aortic Valve Stenosis; Biomarkers; Brachial Artery; Chi-Square Distribution; Compliance; Echocardiography, Doppler; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Pulsatile Flow; Regression Analysis; Risk Assessment; Risk Factors; Severity of Illness Index; Sex Factors; Stroke Volume; Vascular Resistance; Vasodilation; Ventricular Function, Left; Ventricular Remodeling

In aortic stenosis (AS), both reduced systemic arterial compliance and increased valvular load have been shown to contribute to impaired left ventricular (LV) function. However, the relationship between LV function and aortic stiffness has not yet been investigated. We aimed to assess the relationship between aortic stiffness and LV global longitudinal strain (GLS), LV filling pressures (E/E') and B-type natriuretic peptide (BNP) in AS.. A comprehensive echocardiogram was performed in 48 consecutive patients with severe AS (<0.6 cm(2)/m(2)) and preserved LV ejection fraction (≥50%). Aortic stiffness index (beta) was calculated based on aortic diameters measured by echocardiography and blood pressure. Systemic arterial compliance (SAC) and valvulo-arterial impedance (Z(va)) were also determined. Aortic beta index was significantly correlated with Z(va) (r = 0.30, P= 0.03) and SAC (r = -0.29, P = 0.04). GLS (r = 0.45, P = 0.001), E/E' (r = 0.48, P = 0.001) and BNP levels (r = 0.45, P = 0.001) were significantly related to aortic beta index. No significant correlation was found between GLS or E/E' and SAC or Z(va). In multivariate regression analysis, aortic beta index remained correlated with GLS, E/E', and BNP levels.. In patients with severe AS and preserved LV ejection fraction, independently of the valvular load, an increase in aortic rigidity, as assessed by aortic beta index, is independently correlated with reduced LV longitudinal function, increased LV filling pressures, and BNP levels.

Topics: Aged; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Severity of Illness Index; Vascular Stiffness; Ventricular Dysfunction, Left

Topics: Aortic Valve Stenosis; Female; Humans; Male; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Dysfunction, Left

This prospective study aimed to determine to what extent clinical symptoms and neurohumoral activation are improved in patients with severe aortic valve stenosis after transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis.. From June 2008 to June 2009 consecutive patients with symptomatic severe aortic valve stenosis (area<1 cm(2)), age>or=75 years with a logistic EuroSCORE >or=15% or age>60 years plus additional specified risk factors were evaluated for TAVI. Examinations of study patients were performed before and 30 days after TAVI and comprised assessment of quality of life (Minnesota living with heart failure questionnaire, [MLHFQ]) 6-minute walk test, measurement of B-type natriuretic peptide and echocardiography. Aortic valve prosthesis was inserted retrograde using a femoral arterial or a subclavian artery approach.. In 44 consecutive patients (mean age 79.1+/-7 years, 50% women, mean left ventricular ejection fraction 55.8+/-8.5%) TAVI was successfully performed. Follow-up 30 days after TAVI showed a significantly improved quality of life (baseline 44+/-19.1 vs 28+/-17.5 MLHFQ Score, p<0.001) and an enhanced distance in the 6-minute walk test (baseline 204+/-103 vs 266+/-123 m, p<0.001). B-type natriuretic peptide levels were reduced (baseline 725+/-837 vs 423+/-320 pg/ml, p=0.005).. Our preliminary results show a significant clinical benefit and a reduction of neurohormonal activation in patients with severe and symptomatic aortic valve stenosis early after TAVI.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Epidemiologic Methods; Exercise Test; Female; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Male; Middle Aged; Minimally Invasive Surgical Procedures; Natriuretic Peptide, Brain; Quality of Life; Treatment Outcome; Walking

Aortic valve implantation through peripheral vascular access is an option for high-risk patients with severe aortic valve stenosis. The authors aimed to compare the acute effect of endovascular and surgical aortic valve procedures on left ventricular diastolic function.. A case-matched, nonrandomized study.. A university hospital.. Patients with aortic stenosis.. B-natriuretic peptide was measured in 30 patients with a logistic EuroSCORE > or =20% undergoing endovascular aortic valve implantation. Patients were case matched (age, mitral flow propagation velocity, mitral annulus early diastolic velocity, and B-natriuretic peptide measurement) with 30 control patients undergoing surgical aortic valve replacement through sternotomy. Left ventricular diastole was evaluated initially and after valve procedures with echocardiography by mitral flow propagation velocity and mitral annulus early diastolic velocity.. B-natriuretic peptide was similar preoperatively in the 2 groups (346 [188-438] v 367 [211-458] pg/mL) and higher (p = 0.006) in the surgical group postoperatively (389.5 [237-479] v 710.5 [389-822] pg/mL), with a postprocedural statistically significant increase only in the surgical group. Diastolic function was similar in the 2 groups preoperatively, improved postoperatively in the endovascular group, and worsened in the surgical group.. B-natriuretic peptide increased after surgical but not after endovascular aortic valve replacement. Furthermore, endovascular aortic valve implantation acutely improved left ventricular diastolic function as documented by increases in mitral flow propagation velocity and mitral annulus early diastolic velocity.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Case-Control Studies; Diastole; Echocardiography, Transesophageal; Female; Heart Valve Prosthesis Implantation; Humans; Male; Monitoring, Intraoperative; Natriuretic Peptide, Brain; Prospective Studies; Sternotomy; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

The contribution of left ventricular (LV) untwisting to LV suction and early-diastolic filling was previously demonstrated, but this was not yet tested in patients with aortic stenosis (AS). We sought to assess the relationship between LV untwisting and LV filling pressures in patients with severe AS and normal left ventricular ejection fraction (LVEF) using speckle tracking echocardiography.. Sixty-one consecutive patients (66 +/- 9 years) with severe AS, preserved LVEF (63 +/- 6%), and 40 normal subjects (47 +/- 12 years) were prospectively enrolled. A comprehensive echocardiographic examination was performed in all. LV rotation and twisting were assessed using speckle tracking echocardiography. Peak apical back rotation rate, peak LV untwisting rate, and time intervals from QRS onset (ECG) to each of them were measured. Brain natriuretic peptide (BNP) levels were determined in 30 patients. Patients with AS were older than normal subjects (P < 0.001). LV mass, LA volume, LV filling pressures as well as peak apical back rotation rate and time to peak apical back rotation rate were increased in patients (P < 0.05 for all). In patients with AS, both time to peak LV untwisting rate and time to peak apical back rotation rate were significantly related to E/E' ratio and to BNP levels (P < 0.04 for all).. In patients with severe AS and preserved LVEF, there is a significant relationship between LV untwisting and LV filling pressures, suggesting a role for impaired LV untwisting in the pathophysiology of diastolic dysfunction in this setting.

Topics: Aged; Analysis of Variance; Aortic Valve Stenosis; Case-Control Studies; Diastole; Echocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Regression Analysis; Severity of Illness Index; Statistics as Topic; Stroke Volume; Torsion, Mechanical; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

In aortic stenosis (AS), the increased afterload results in progressive structural and functional changes that precede the development of symptoms. We hypothesized that the detection of abnormalities in left ventricular long-axis function could identify patients with asymptomatic AS at increased risk of events. We prospectively examined the outcome of 126 patients with asymptomatic AS who underwent a comprehensive echocardiographic examination, including tissue Doppler imaging. B-type natriuretic peptide (BNP) was measured in all patients. During a median follow-up period of 20.3 + or - 17.8 months, 6 patients died, 8 developed symptoms but did not undergo surgery, and 48 underwent aortic valve replacement. On multivariate Cox regression analysis, the parameters associated with the predefined outcome were gender (p = 0.048), left atrial area index (p = 0.011), systolic annular velocity (p = 0.016), E/Ea ratio (p = 0.024), late diastolic annular velocity (p = 0.023), and BNP (p = 0.012). Using receiver operating characteristics curve analysis, a left atrial area index of > or = 12.4 cm(2)/m(2), systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events. In conclusion, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis; Ventricular Dysfunction, Left

N-terminal pro-B-type natriuretic peptide (Nt-proBNP) is a peptide released from myocardium in response to ventricular wall stress and dysfunction. Nt-proBNP plasma levels are elevated in a variety of cardiovascular disorders and are largely used for diagnosis and treatment of cardiac diseases. The cardiac cycle efficiency (CCE) is a haemodynamic variable that represents the left ventricle wall stress and the heart's effort to maintain an adequate blood flow to tissues. We investigated the relationship between Nt-proBNP and CCE values in patients undergoing cardiac surgery. Twenty-five patients undergoing aortic valve replacement were studied. Plasma Nt-proBNP concentrations were performed by electroluminescence immunoassay before starting surgery (t0), at the end of extracorporeal circulation (t1) and 3 hours after surgery (t2). CCE measurements were acquired at the same intervals and correlations with Nt-proBNP levels were calculated. Nt-proBNP plasma concentration was 1430 ± 341 pg/ml at t0, peaked significantly at t1 (2129 ± 561 pg/ml, p<0.001) and moderately decreased at t2 (1924 ± 477 pg/ml, p<0.05). A direct correlation between Nt-proBNP measured at t0 and t1 was found (r=0.91, p<0.001). Overall, a negative correlation between CCE and proBNP values was found (r=-0.89, p<0.01). Correlations between CCE and Nt-proBNP were -0.91, -0.83 and -0.88, at t0, t1 and t2, respectively (p<0.01). Nt-proBNP levels reflect the severity of left ventricle dysfunction in patients undergoing cardiac surgery. CCE correlated well with serum Nt-proBNP levels and seems to be a useful variable to monitor the left ventricular stress and recovery during the various phases of surgery.

Topics: Aged; Algorithms; Aortic Valve; Aortic Valve Stenosis; Cardiac Surgical Procedures; Echocardiography; Female; Hemodynamics; Humans; Male; Monitoring, Physiologic; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Ventricular Function, Left

Transapical aortic valve replacement (TAVR) is increasingly being applied in conventionally inoperable patients with aortic stenosis. The utility of the cardiac marker NT-pro-BNP has yet not been assessed in this setting.. NT-pro-BNP was assessed preoperatively, postoperatively (day 1, 3, 5 and 8) and 2 months after the intervention in 31 consecutive patients (13 men, 18 women; median age 84) undergoing TAVR and the association with baseline characteristics and outcome was analysed.. Baseline NT-pro-BNP was associated with baseline creatinine, left-ventricular mass index and NYHA class and predicted regression of LV-mass after 2 months. There was no correlation of NT-pro-BNP with measures of the aortic valve function before or after replacement. The increase of NT-pro-BNP 3 days after TAVR was inversely associated with a functional improvement of >or=1 NYHA class at 2 months. Baseline NT-pro-BNP was not associated with 2-month mortality and major adverse events (death/neurological deficit), whereas the postoperative increase of NT-pro-BNP after TAVR showed a slightly significant inverse and the EuroSCORE a significant correlation.. In multimorbid patients undergoing TAVR, NT-pro-BNP independently predicted regression of LV-mass after 2 months and early decrease of NT-pro-BNP postoperatively indicated improvement of functional capacity at 2 months. There was no association of NT-pro-BNP with 2-month mortality.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Female; Heart Valve Prosthesis; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Treatment Outcome

The present study sought to assess the effect of global left ventricular (LV) afterload on LV myocardial systolic function in patients with aortic stenosis (AS) and preserved LV ejection fraction.. We prospectively examined the LV myocardial deformation (i.e. longitudinal, radial, and circumferential) by two-dimensional speckle tracking in 173 patients with asymptomatic severe AS. Thirty-eight patients (22%) had low flow as determined by a low stroke volume index (or=5 mmHg mL/m(2)). Systemic arterial compliance (P = 0.001), circumferential myocardial deformation (P = 0.024), and left atrial area index (P = 0.04) were independently associated with increased global LV load in multivariable analysis. Of note, LV ejection fraction was not identified as a determinant of low flow or increased afterload.. In asymptomatic patients with severe AS, LV ejection fraction markedly underestimates the extent of myocardial systolic impairment. Intrinsic myocardial dysfunction is particularly common in patients with increased global LV afterload, and especially in the subset of patients with low-flow AS.

Topics: Aged; Analysis of Variance; Aortic Valve Stenosis; Cardiac Output; Echocardiography; Female; Heart Ventricles; Hemodynamics; Humans; Linear Models; Logistic Models; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; ROC Curve; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

It has been shown previously that elevated plasma levels of B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-pro-BNP) are related to the degree and progression of native aortic valve disease. In addition, NT-pro-BNP levels have been shown to decrease after successful aortic valve replacement (AVR). The presence of a valve prosthesis-patient mismatch (PPM) may affect the beneficial effects of AVR, however. The study aim was to investigate the relationship between PPM and NT-pro-BNP plasma levels late after AVR.. A series of consecutive patients (42 males, 31 females; mean age 66 +/- 13 years) who had undergone isolated AVR between May 2004 and July 2007 was enrolled into the study. Patients with preoperative moderate to severe mitral regurgitation, coronary artery disease, left ventricular (LV) dysfunction (ejection fraction <45%) and serum creatinine >150 mmol/l were excluded. PPM was defined severe as an indexed effective orifice area (EOAi) < or = 0.65 cm2/m2, or moderate when the EOAi was 0.66-0.85 cm2/m2. Plasma NT-pro-BNP levels and echocardiographic assessments were performed in all patients during routine follow up after surgery.. The patients received either a biological (n = 42) or mechanical (n = 31) prosthesis. Among the patients, 21 had no PPM, 27 moderate PPM, and 25 severe PPM. At a median follow up of 18 months, the mean NT-pro-BNP plasma level was 532 pg/ml (95% CI: 393.1-671.6), and the mean LV mass index (LVMI) 120 +/- 4 g/m2, the LVEF 60 +/- 1%, the peak aortic prosthesis gradient 28 +/- 2 mmHg, and the EOAi 0.74 +/- 0.02 cm2/m2. Multivariate statistical analysis showed that NT-pro-BNP level correlated with age (beta = 0.57, p<0.0001), LVMI (beta = 0.32, p = 0.02), NYHA class (beta = 0.50, p = 0.003) and EOAi (beta = -0.38, p = 0.02).. The study results showed that NT-pro-BNP levels were independently related to PPM late after isolated AVR in patients with preserved LV function. However, further investigations are required to confirm these findings and to identify their clinical implications.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Echocardiography; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prosthesis Fitting; Ventricular Function, Left

To test whether symptoms revealed on exercise testing in patients with moderate or severe aortic stenosis are associated with changes in left ventricular systolic function and to investigate the ability of resting measures to predict peak cardiac index.. In a prospective study of asymptomatic aortic stenosis, 38 patients with a median age of 63 years (range 29-83) and an effective aortic orifice area by the continuity equation of less than 1.5 cm(2) had echocardiography, measurement of blood B-type natriuretic peptide (BNP) level and exercise haemodynamic testing using an inert gas rebreathing device.. Revealed symptoms occurred in 10 patients in whom peak cardiac index (p=0.002), stroke index (p=0.024) and maximum oxygen consumption (VO(2)) (p=0.003) were lower than in those without symptoms. Univariate predictors of peak cardiac index were Doppler tissue peak systolic velocity (p=0.004, r=0.45), the ratio of peak transmitral E velocity to Doppler tissue Ea velocity (p=0.039, r=-0.34) and log BNP (p<0.001, r=-0.71). The only independent predictor of peak cardiac index was the log BNP level (p<0.001, r=-0.71).. Revealed symptoms on treadmill exercise in apparently asymptomatic aortic stenosis were associated with lower peak myocardial VO(2) and lower peak stroke index during exercise. The strongest resting predictor of revealed symptoms and of peak cardiac index was the blood BNP level.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography; Exercise; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Ventricular Dysfunction, Left

This prospective study was designed to evaluate the hemodynamic results of transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) and the effects on left ventricular function.. From June 2008 to June 2009, consecutive patients with severe symptomatic aortic valve stenosis (aortic valve area <1 cm(2)) and the indication for TAVI were included. Aortic valve prosthesis was inserted retrograde. Examinations of study patients were performed before, 30 days, and 6 months after TAVI and comprised measurement of B-type natriuretic peptide and echocardiography. Severe prosthesis-patient mismatch was defined as an indexed effective aortic valve area < or =0.65 cm(2)/m(2).. In 39 patients, follow-up examinations were performed after TAVI. Severe prosthesis-patient mismatch seldom occurred (n = 1), but mild to moderate aortic valve regurgitation due to paravalvular leaks was common (n = 24, 62%). After 6 months, left ventricular mass index declined (158 +/- 46 vs 138 +/- 45 g/m(2), P = .001), and peak early diastolic mitral annular velocity (E') and peak systolic mitral annular velocity (S') increased (P = .004 and P < .001, respectively). B-type natriuretic peptide levels decreased (744 +/- 708 at baseline vs 367 +/- 273 at 30 days, P = .003, 279 +/- 186 pg/mL at 6 months, P = .001). Left ventricular diameters and ejection fraction remained unchanged.. Despite the high incidence of paravalvular regurgitation after TAVI, hemodynamic results were favorable. Furthermore, TAVI had positive effects on left ventricular remodeling and improved neurohormonal activity, myocardial hypertrophy, and diastolic function.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiac Volume; Echocardiography, Doppler; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Male; Natriuretic Peptide, Brain; Postoperative Complications; Prospective Studies; Ventricular Dysfunction, Left

Symptom onset is a critical point in natural course of aortic stenosis and the most important indication for aortic valve replacement. The aim of the study was to evaluate the role of natriuretic peptides level in the assessment of symtomatic status of patients with severe aortic stenosis and the preserved left ventricular systolic function.. In 67 patients with isolated severe aortic stenosis symptomatic status, transthoracic echocardiography, and BNP and NT-proBNP plasma level were assesed. Natriuretic peptides levels were also measured in 36 healthy controls.. BNP and NT-proBNP levels were significantly higher in the patients with aortic stenosis compared with the healthy controls. The symptomatic patients had a higher level of natriuretic peptides than the asymptomatic ones (BNP 118 [29-266] vs. 79 [44-90] pg/mL, p < 0.001; NT-proBNP 258 [67-520], vs. 79 [77-112] pmol/L, p < 0.0001). Natriuretic peptides levels increased with the severity of NYHA class. NT-proBNP level higher than 122 pmol/L was a cutoff value for detection of symptoms in the patients with severe aortic stenosis.. The levels of natriuretic peptides were significantly higher in the patients with symptomatic aortic stenosis, and increased with NYHA class. Measurement of natriuretic peptides levels could be important addition to clinical and echocardiographic assesment in determing optimal timing for valve replacement in aortic stenosis.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments

The aim of this study was to evaluate the value of clinical and echo-Doppler parameters for the prognosis of unoperated severe aortic stenosis (AS).. Approximately one-third of severe, symptomatic AS patients are denied surgery. Risk stratification of unoperated AS is important to determine eligibility for percutaneous aortic valve replacement, an evolving treatment option for AS patients deemed suboptimal for surgical aortic valve replacement.. We retrospectively compared clinical and echo-Doppler parameters between survivors and nonsurvivors of 125 patients with unoperated severe AS.. The 1-year survival rate was 62.4%. In univariate analysis, survivors compared with nonsurvivors were younger (80.0 ± 10.9 years vs. 84.9 ± 11.1 years, p = 0.02), had a greater left ventricular ejection fraction (LVEF) (55 ± 15% vs. 50 ± 16%, p = 0.042), a higher left ventricular stroke volume (63 ± 19 ml vs. 56 ± 13 ml, p = 0.015), a lower E/E' ratio (12.19 ± 5.7 vs. 16.87 ± 7.43, p < 0.001), and a lower prevalence of E/E' > 15 (20% vs. 55%, p < 0.001). Symptomatic status was nonsignificantly different between survivors and nonsurvivors. In patients with an LVEF ≥ 50%, the subgroup with E/E' ≤ 15 and with E/E' > 15 had a 73.8% and 47.8% 1-year survival rate, respectively (p = 0.027). In the patients with an LVEF < 50%, the patients with E/E' ≤ 15 and those with E/E' > 15 demonstrated a 70.6% and 22.3% 1-year survival rate, respectively (p = 0.003). In multivariate analysis, significant predictors of mortality were E/E' > 15 and a combination of E/E' > 15 and B-type natriuretic peptide > 300 ng/ml: adjusted mortality risk 2.34 (95% confidence interval (CI) 1.27 to 4.33, p = 0.0072) and 2.59 (95% CI 1.21 to 5.55, p = 0.014), respectively.. The E/E' ratio is the single most predictive clinical and echo-Doppler parameter in the assessment of overall prognosis in patients with unoperated severe AS. LVEF was a significant predictor of survival only in the univariate analysis. B-type natriuretic peptide alone was not a predictor of prognosis in the study population. However, the combination of E/E' and B-type natriuretic peptide is even more predictive of the 1-year prognosis.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Pressure; Echocardiography, Doppler; Female; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Pulmonary Artery; Retrospective Studies; Risk Assessment; ROC Curve; Severity of Illness Index; Stroke Volume; Treatment Outcome

Limited data are available regarding the impact of pressure or volume overload on the clinical or echocardiographic parameters and the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with chronic severe aortic valve diseases. We aimed to investigate and compare the relationships between these parameters in such patients.. One hundred twenty-four consecutive patients who underwent aortic valve replacement for chronic severe aortic valve diseases were enrolled. Plasma NT- proBNP was measured and echocardiographic parameters were recorded before surgery, before discharge and 12 months after surgery.. NT-proBNP levels were significantly higher in patients with aortic regurgitation (AR) (n = 63) than in those with aortic stenosis (n = 61) (1,836.0 ± 376.1 vs. 508.4 ± 74.5 pg/ml, p = 0.001). There was a significant relationship between NT-proBNP levels and left ventricular mass index (LVMI) in AR (r = 0.436, p = 0.002) and a weaker, but significant, relationship between NT-proBNP levels and LVMI in aortic stenosis patients (r = 0.290, p = 0.046). In the AR group, preoperative NT-proBNP levels positively correlated with LVMI regression during the 12 months after surgery (r = 0.488, p = 0.001).. NT-proBNP levels may reflect LVMI changes that are caused by volume overload rather than pressure overload in chronic aortic valve diseases. Higher preoperative NT-proBNP levels may predict left ventricular reverse remodeling early after surgery for chronic severe AR.

Topics: Aortic Valve Insufficiency; Aortic Valve Stenosis; Chi-Square Distribution; Comorbidity; Echocardiography; Female; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Statistics, Nonparametric; Treatment Outcome; Ventricular Dysfunction, Left

Apelin is a newly discovered inotropic peptide tentatively linked up with the pathophysiology of heart failure (HF). To further assess the role of apelin in HF, we measured its transcardiac arteriovenous gradients in patients with left ventricular pressure overload with or without HF and in patients with structurally normal hearts. Blood samples from the aortic root and coronary sinus were drawn from 49 adult patients undergoing preoperative cardiac catheterization for severe aortic valve stenosis (AS). Similar samples were taken from 12 control patients with structurally normal hearts undergoing electrophysiological studies. Plasma apelin was determined by enzyme immunoassay. In the control group, apelin decreased from a median of 0.39 (0.16-1.94) ng/ml in the aortic root to 0.18 (0.13-1.04) ng/ml in the coronary sinus (P = 0.004). In AS patients free of HF (n = 33), apelin concentration remained unaltered across the heart, but in those with HF (n = 15) apelin rose from a median of 0.26 (0.20-0.82) ng/ml in the aorta to 0.45 (0.24-1.17) ng/ml in the coronary sinus (P = 0.002). The transcardiac apelin gradients differed statistically highly significantly across the three groups (P = 0.00005), and each of the two-group differences was also statistically significant (P < 0.05). In conclusion, left ventricular pressure overload changes the transcardiac arteriovenous differences of circulating apelin. Although normal hearts extract apelin from the coronary blood, hearts failing due to left ventricular pressure overload release apelin into the circulation. Loss of cardiac apelin may be involved in the mechanisms of HF development in AS.

Topics: Aged; Aorta; Aortic Valve Stenosis; Apelin; Biomarkers; Case-Control Studies; Coronary Sinus; Echocardiography, Doppler; Female; Heart Failure; Humans; Hypertrophy, Left Ventricular; Immunoenzyme Techniques; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

To evaluate the diagnostic value of NT-proBNP in patients with aortic stenosis (AS), analyze the relation of NT-proBNP to NYHA functional class and echocardiographic findings.. Measured the whole venous blood of NT-proBNP with enzyme linked immuno sorbent assay in 40 aortic stenosis patients (AS group) and 76 normal subjects (control group). We assessed the diagnostic value of NT-proBNP for aortic stenosis, and related NT-proBNP to clinical NYHA functional class and echocardiographic findings.. Compared to controls, NT-proBNP levels had significantly higher in patients with aortic stenosis (P < 0.01). The level of NT-proBNP was gradually and significantly increased with the NYHA functional II, III and IV class compared to controls (all P < 0.01). NT-proBNP was significantly (3.5 times) higher in mild/moderate stenosis group than that in control group (2.95 ± 0.48 vs 2.63 ± 0.10, P < 0.05), and was significantly (6.0 times) higher in severe stenosis group than that in control group (3.16 ± 0.50 vs 2.63 ± 0.10, P < 0.01). LVMI was significantly (1.7 times) higher in mild/moderate stenosis group than that in control group (169 ± 51 vs 100 ± 22, P < 0.01), and was significantly (2.1 times) higher in severe stenosis group than that in control group (212 ± 86 vs 100 ± 22, P < 0.01). The NT-proBNP values of 1150 ng/L and 1356 ng/L were determined as the best cutoff values for the diagnosis of patients with mild/moderate (AUC = 0.657, P < 0.05) and severe aortic stenosis (AUC = 0.848, P < 0.01), the sensitivity, specificity and accuracy were 61.11% and 77.30%, 69.74% and 96.10%, 68.09% and 91.80%. Log (NT-proBNP) was significantly positively related with LVEDD, LVMI and mean transvalvular pressure gradient (MTPG) (all P < 0.05), and negatively related with LVEF (P = 0.01) in univariate analysis. In multiple regression analyses, NYHA functional class, LVEF and Log (MTPG) was independently associated with NT-proBNP.. NT-proBNP is valuable for the diagnosis of patients with aortic stenosis. NT-proBNP has correlation with the heart function and severity of the aortic stenosis.

Topics: Aged; Aortic Valve Stenosis; Case-Control Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

To evaluate the diagnostic value of NT-proBNP in aortic stenosis (AS) patients with heart failure.. We measured the whole venous blood of NT-proBNP with enzyme linked immuno sorbent assay (Biomedica, Vienna, Austria) in 40 AS patients with heart failure and 76 normal subjects and assessed the diagnostic value of NT-proBNP for heart failure.. NT-proBNP levels were significantly higher in AS patients with heart failure compared to controls (P < 0.01). The level of NT-proBNP increased in proportion to the increase of NYHA functional classes (all P < 0.01). The level of NT-proBNP was similar between compensated heart failure group and control group (P > 0.05) and significantly (8 times) increased in decompensated heart failure group (P < 0.01 vs. control group). NT-proBNP level was also significantly higher in LVEDD > 50 mm group than that in LVEDD ≤ 50 mm group (P < 0.05) and in LVEF ≤ 60% group than that in LVEF > 60% group (P < 0.01). Patients with atrial fibrillation also had higher NT-proBNP levels compared to those with sinus rhythm (P < 0.05). The NT-proBNP value of 1360 ng/L was determined as the best cutoff value for the diagnosis of AS patients with heart failure (AUC = 0.762, P < 0.01) and decompensated heart failure (AUC = 0.997, P < 0.01), the sensitivity, specificity and accuracy were 67.50% and 100.00%, 96.05% and 96.05% and 86.21% and 95.83%, respectively. Log (NT-proBNP) was positively related with NYHA functional class and negatively related with LVEF in univariate analysis and multiple regression analyses (P < 0.05). NT-proBNP was independent correlative with NYHA functional class and LVEF.. NT-proBNP has a fairly good diagnostic potential for the identification of AS patients with heart failure. The accuracy is 86.21% for the diagnosis of AS patients with heart failure and 95.83% for decompensated heart failure with the diagnostic cutoff value of 1360 ng/L.

Topics: Adult; Aged; Aortic Valve Stenosis; Case-Control Studies; Female; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

B-type natriuretic peptide (BNP) has been shown to predict outcomes after conventional aortic valve replacement. The aim of the present study was to investigate whether BNP also predicts the outcomes after transcatheter aortic valve implantation (TAVI). A total of 58 patients (36 men, age 84 ± 5 years) underwent TAVI in our institution for severe aortic stenosis (aortic valve area 0.6 ± 0.1 cm², mean gradient 41 ± 15 mm Hg) at high risk of surgery (logistic European System for Cardiac Operative Risk Evaluation 34 ± 17%). BNP was measured before and 24 hours after TAVI. The 30-day survival rate was 91%. Although the baseline clinical and hemodynamic characteristics were similar among the 30-day survivors (n = 53) and nonsurvivors (n = 5), the BNP levels were significantly lower in the 30-day survivors, at both baseline (463 ± 265 vs 1,067 ± 655 pg/ml; p = 0.005) and 24 hours after TAVI (488 ± 238 vs 1,632 ± 1,028 pg/ml; p <0.0001). The BNP levels were significantly greater in patients experiencing one major adverse event at 30 days. On multivariate analysis, only BNP levels (baseline value and change at 24 hours) were independent predictors of 30-day survival. Kaplan-Meier analysis showed that 30-day survival was significantly lower in patients with than in those without both a baseline BNP level >428 mg/dl (p = 0.04) and a significant BNP increase of >170 pg/ml at 24 hours after TAVI (p = 0.001). In conclusion, BNP is a strong predictor of 30-day outcomes after transcatheter aortic valve implantation, at both baseline and 24 hours after the procedure.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Belgium; Biomarkers; Cardiac Catheterization; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Survival Rate; Treatment Outcome

Older patients with aortic stenosis cannot always be offered conventional surgical aortic valve replacement at an acceptable risk. Transcatheter aortic valve implantation (TAVI) is currently considered an alternative treatment option with lower periprocedural risks. However, its effect on post-TAVI quality of life and clinical improvement has not been systematically and prospectively evaluated in those of advanced age. Thus, the aim of the present study was to assess the clinical improvement in geriatric patients after TAVI, with a special emphasis on quality of life. In the present study, we assessed the quality of life and brain natriuretic peptide in patients aged >80 years, before and 6 months after transfemoral CoreValve implantation. Of 87 prospectively studied patients with severe, symptomatic aortic stenosis at an age of ≥81 years, 80 survived for 6 months and were able to attend the follow-up visit with a quality of life assessment, using the Medical Outcomes Trust Short Form 36-Item Health Survey (average age 86 ± 2.9 years). The average scores of all 8 health components had improved significantly after TAVI. The greatest gain was seen in physical functioning (improvement from 23.4 ± 6.0 to 67.8 ± 13.7; p <0.001). The lowest gain was seen in bodily pain (improved from 37.5 ± 9.4 to 51.3 ± 11.5; p <0.05). Similarly, both the physical and the mental component summary scores improved significantly. This was consistent with significant improvement in brain natriuretic peptide levels (5,770 ± 8,016 to 1,641 ± 3,650 ng/L; p <0.0001). In conclusion, the results of the present study have shown a significant clinical benefit from TAVI in a patient population aged ≥81 years.

Topics: Age Factors; Aged, 80 and over; Aortic Valve Stenosis; Cardiac Catheterization; Female; Follow-Up Studies; Germany; Heart Valve Prosthesis Implantation; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Quality of Life; Risk Factors; Surveys and Questionnaires; Survival Rate; Treatment Outcome

Endothelin-1 (ET-1) and B-type natriuretic peptide (BNP) have been reported to be involved in numerous cardiovascular diseases. The study aim was to monitor the circulating plasma levels of these peptides in patients affected by aortic disease, and to identify any changes in such levels after surgical treatment.. A total of 81 patients (52 males, 29 females; mean age 64 +/- 11 years) with aortic disease underwent surgery. The conditions included aortic valve stenosis (n=36), aortic valve regurgitation (n=11), ascending aortic aneurysm (n=6), and combined ascending aortic aneurysm and valvulopathy (n=28). Circulating plasma levels of ET-1 and BNP were measured in all patients before and at 12 months after surgery.. Compared to the preoperative situation, significant decreases were found postoperatively in plasma levels of ET-1 (4.2 +/- 0.1 versus 3.1 +/- 0.1 pM; p < 0.001) and BNP (0.071 versus 0.017 ng/ml; p < 0.001), combined with an increased cardiac function and decreased ventricular dimensions. The preoperative levels of both peptides were similar in all patient groups, and were decreased to a similar extent regardless of the diagnosis. Basal levels of ET-1 were higher in the trileaflet aortic valve compared to the bicuspid valve (4.0 +/- 0.1 versus 3.6 +/- 0.1 pM; p = 0.04).. Circulating plasma levels of ET-1 and BNP were decreased after surgery for aortic valve disease. The decrease was unrelated to the presence of ascending aortic aneurysm, and most likely represents a response to cardiac remodeling and the improved functional status of the patients.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Blood Vessel Prosthesis Implantation; Down-Regulation; Endothelin-1; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Recovery of Function; Stroke Volume; Sweden; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Plasma levels of brain natriuretic peptide (BNP) have been shown to correlate to aortic stenosis severity and are predictive of symptom development and survival. They also predict postoperative outcomes after valve replacement in patients with aortic stenosis. The early evolution of N-terminal-pro-BNP (NT-pro-BNP) levels after 50 aortic balloon valvuloplasty procedures performed in 45 patients was investigated. The mean NT-pro-BNP concentration decreased from 7,048 +/- 7,636 pg/ml at baseline to 5,309 +/- 6,150 pg/ml at 1 to 3 days after the procedure (mean difference 1,739 pg/ml, 95% confidence interval 804 to 2,675, p = 0.001). The absolute reduction in NT-pro-BNP levels correlated to the reductions in the maximum and mean transvalvular pressure gradients (on echocardiography: c = 0.57, p = 0.004, and c = 0.54, p = 0.012, respectively; invasively: c = 0.54, p = 0.025, and c = 0.39, p = 0.019). In conclusion, NT-pro-BNP levels decrease early after aortic balloon valvuloplasty in patients with severe aortic stenosis at high surgical risk.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Catheterization; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Topics: Aortic Valve Stenosis; Elasticity Imaging Techniques; Exercise Test; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment

Exercise-induced symptoms are associated with early changes in left ventricular (LV) function. Blood B-type natriuretic peptide (BNP) and tissue Doppler indices (tDi) also reflect early LV dysfunction, and may therefore predict the development of symptoms. The study aim was to compare BNP levels and tDi for predicting symptoms on treadmill exercise in apparently asymptomatic aortic stenosis (AS).. A total of 65 patients (mean age 66 years) with an aortic effective orifice area <1.5 cm2 who were asymptomatic on formal questioning, underwent transthoracic echocardiography, measurement of blood BNP level, and exercise testing using a modified Bruce protocol.. A blood BNP level >58 pg/ml had a sensitivity of 86% and specificity of 64% (AUC = 0.81) for the development of symptoms on exercise testing. The combined tDi index of peak systolic shortening velocity <8 cm/s and E/Ea >15 had a sensitivity of 52% and specificity of 73%. In patients with no symptoms on exercise, 27% with a blood BNP level >58 pg/ml compared to 7% with a level < or =58 pg/ml developed symptoms during follow up.. The study results suggested that patients with a blood BNP level < or =58 pg/ml can be seen up to one year, while those with a BNP level >58 pg/ml required exercise testing and a more frequent follow up. The combined tissue Doppler indices gave a similar, but less accurate, stratification.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Aortic Valve Stenosis; Elasticity Imaging Techniques; Exercise Test; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Assessment; ROC Curve

The accuracy of the logistic EuroSCORE (logES), a widely used risk prediction algorithm for cardiac surgery including aortic valve surgery, usually overestimates observed perioperative mortality. Elevated brain natriuretic peptide (BNP) in symptomatic patients with aortic stenosis (AS) is associated with a poor short-term outcome after aortic valve replacement. We aimed to compare BNP with the logES for predicting short- and long-term outcome in symptomatic patients with severe AS undergoing aortic valve replacement. We prospectively studied 144 consecutive patients referred for aortic valve replacement (42% women, 73 +/- 9 years, mean aortic gradient 51 +/- 18 mm Hg, and left ventricular ejection fraction 61 +/- 11%) undergoing either isolated aortic valve replacement (58%) or combined to bypass grafting. Both plasma BNP and logES was estimated before surgery. The median BNP plasma level and logES were 157 pg/ml (interquartile range [IQR] 61 to 440) and 6.6% (IQR 4.2 to 12.2), respectively. The perioperative mortality was 6% and the overall mortality by the end of the study was 13%. Patients with logES >10.1% (upper tertile) had a higher risk of dying over time (hazard ratio [HR] 2.86, p = 0.037), as had patients with BNP >312 pg/ml (HR 9.01, p <0.001). Discrimination (based on C statistic) and model performance (based on Akaike information criterion) were better for BNP than for logES. At the bivariable analysis, only BNP was an independent predictor of death (HR 8.2, p = 0.002). Preoperative BNP was even more accurate than logES in predicting outcome. In conclusion, in symptomatic patients with severe AS, high preoperative BNP plasma level and high logES confirm their predicting value for short- and long-term outcome.

Topics: Age Factors; Aged; Aortic Valve; Aortic Valve Stenosis; Coronary Artery Bypass; Coronary Artery Disease; Female; Follow-Up Studies; Heart Valve Prosthesis; Hospital Mortality; Humans; Male; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Preoperative Care; Prospective Studies; Severity of Illness Index

A 34-year-old woman was in her 24th week of her second pregnancy when she suffered a recurrence of her congenital aortic valve stenosis (CAS), previously treated by surgical commissurotomy. She was dyspneic on only mild exertion. The first pregnancy had been uneventful.. RR was 110/70 mmHg. The electrocardiogram showed left ventricular hypertrophy and myocardial damage. Echocardiography revealed a maximal systolic gradient of 155 mm Hg (mean gradient 104 mm Hg). The blood picture showed a pregnancy-related mild anemia and haemodilution.. The patient was hospitalized as a precaution from the 31st week of pregnancy onwards. An elective section was performed under intubation aneasthesia in the 36th week of pregnancy. The aortic valve was electively replaced 13 weeks after delivery.. Patients with a CAS who had been treated palliatively with a commissurotomy should be carefully and regularly monitored to avoid recurrent stenosis. Close collaboration with the delivery team is essential.

Topics: Adult; Aortic Valve; Aortic Valve Stenosis; Cesarean Section; Echocardiography; Electrocardiography; Female; Heart Valve Prosthesis Implantation; Humans; Laser-Doppler Flowmetry; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications, Cardiovascular; Recurrence

In aortic stenosis (AS), serum levels of brain natriuretic peptide (BNP) are elevated, but the relation of this elevation to the degree of left ventricular hypertrophy (LVH) remains unclear. The study aim was to assess the relationship between BNP and LVH (expressed as LV mass index, LVMI) and LV wall thickness index (WThI) in a group of patients.. A total of 147 patients with AS (85 men, 62 women; mean age 61 +/- 12 years) each underwent echocardiography and serum BNP analysis. The correlation between serum BNP level and LVH was investigated, with patient gender, age, NYHA class, AS severity and presence of coronary artery disease also being taken into account.. Among AS patients, serum BNP levels ranged from 3 to 2010 pg/ml; mean BNP levels were similar in women and men (213 +/- 302 and 253 +/- 375 pg/ml, respectively). The BNP level also correlated directly with the LVMI (r = 0.55; p <0.0001), WThI (r = 0.26; p <0.001), end-diastolic dimension (r = 0.43; p <0.0001), mean aortic gradient (r = 0.25; p = 0.002), age (r = 0.27; p = 0.001); and correlated inversely with the LV ejection fraction (r = -0.52; p <0.0001). Eccentric LVH was associated with a significantly higher serum BNP level (506 +/- 558 pg/ml) than concentric-type hypertrophy (190 +/- 254 pg/ml; p = 0.002).. The measurement of serum BNP levels is of potential value when monitoring LVH in aortic stenosis patients.

Topics: Age Factors; Aortic Valve Stenosis; Biomarkers; Diastole; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ultrasonography

Patients with severe aortic stenosis (AS) require valve replacement before development of irreversible left ventricular (LV) dysfunction. It has been postulated that Doppler tissue imaging (DTI) parameters are more sensitive to detect subtle LV dysfunction compared with conventional echocardiographic parameters.. We sought to assess early LV dysfunction with DTI-derived echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with severe AS and normal LV ejection fraction.. A total of 29 patients (mean age 65 +/- 12 years, 15 male) with symptomatic severe AS and 17 control subjects were included in the study. DTI was performed at the level of the mitral lateral (m(lat)) and septal (m(sep)) annulus. Systolic (Sm), early (Em), and late (Am) diastolic velocities were measured, and E/Em ratio was calculated. NT-proBNP was determined by an electrochemiluminescence immunoassay.. Baseline characteristics between patients and control subjects were similar regarding LV ejection fraction and mitral inflow E/A ratio. However, patients with AS had significantly lower DTI values (Sm, Em, Am) compared with control subjects. Moreover, LV filling pressures, expressed by the E/Em ratio, were significantly higher in patients. Correlation analysis showed a relationship between the natural logarithm of NT-proBNP and aortic valve area, Sm(lat), and E/Em((sep)) ratio. Using stepwise multiple linear regression, Sm(lat) was found to be independently related to NT-proBNP.. In patients with severe AS and normal LV ejection fraction, DTI showed LV systolic and diastolic dysfunction compared with control subjects. DTI-derived variables, and especially Sm(lat), were correlated with NT-proBNP levels.

Topics: Aged; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) is related to symptomatic status and outcome in aortic stenosis (AS) patients. Carbohydrate antigen 125 (CA125) demonstrated recently a BNP-like behaviour in patients with congestive heart failure (CHF) but has never been studied in AS patients. We aimed to assess the role of CA125 and BNP in AS patients.. CA125 and BNP blood levels, transthoracic echocardiography and independent evaluation of CHF symptoms were obtained in 64 consecutive patients (76+/-9 years; 35 males) with AS (valve area 0.9+/-0.3 cm(2)). A pre-specified combined end-point consisting of cardiac mortality, urgent aortic valve replacement and hospitalization for CHF was considered. The median follow-up was 8 months (interquartile range 4.5-10 months).. Both CA125 and BNP have accurately identified patients with III-IV NYHA class: area under the ROC curve was 0.85 for CA125 and 0.78 for BNP (best cut-offs of 10.3 U/mL and 254.64 pg/mL respectively) and were independently correlated to left ventricular ejection fraction. Fifty-two percent of patients with CA125>or=10.3 U/mL vs. 13% with CA125<10.3 U/mL (p<0.01) and 65% patients with BNP>or=254 pg/mL vs. 7% with BNP<254 pg/mL (p<0.001) have reached the end-point.. Both CA125 and BNP levels are significantly correlated with NYHA class and outcome in patients with AS. CA125 blood level assessment (less expensive) may improve the clinical management in this setting.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; CA-125 Antigen; Female; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Research Design

Brain natriuretic peptide (BNP) levels correlate with prognosis in patients with cardiac disease and may be useful in the risk stratification of cardiac patients undergoing noncardiac surgery (NCS). The objective of this study was to examine whether BNP levels predict perioperative events in cardiac patients undergoing NCS.. Patients undergoing NCS with at least 1 of the following criteria were included: a clinical history of congestive heart failure (CHF), ejection fraction <40%, or severe aortic stenosis. All patients underwent echocardiography and measurement of BNP performed using the ADVIA-Centaur BNP assay (Bayer HealthCare). Clinical endpoints were death, myocardial infarction or pulmonary congestion requiring intravenous diuretics at 30 days of follow-up.. Forty-four patients were entered into the study; 15 patients (34%) developed cardiac postoperative complications. The mean BNP level was 1,366 +/- 1,420 pg/ml in patients with events and 167 +/- 194 pg/ml in patients without events, indicating a highly significant difference (p < 0.001). The ROC area under the curve was 0.91 (95% CI 0.83-0.99) with an optimal cutoff of >165 pg/ml (100% sensitivity, 70% specificity).. BNP levels may predict perioperative complications in cardiac patients undergoing NCS, and the measurement of BNP should be considered to assess the preoperative cardiac risk.

Topics: Aged; Aortic Valve Stenosis; Female; Heart Diseases; Heart Failure; Humans; Lung Diseases; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Postoperative Complications; Risk Assessment; Sensitivity and Specificity; Surgical Procedures, Operative

Both raised plasma levels of B-type natriuretic peptide (BNP) and an abnormal exercise response predict adverse clinical outcomes in aortic stenosis (AS). This study examines the relationship between the response to treadmill exercise and plasma levels of BNP in AS.. 34 asymptomatic patients with moderate or severe AS (mean valve area 0.96+/-0.3 cm(2)) and 15 age matched controls underwent echocardiography, treadmill exercise testing, and BNP analysis. Compared to control subjects, AS patients had a higher left ventricular mass index, (133+/-50 vs 106+/-24 g/m(2), p=0.03), higher E/E' ratio, (10.6+/-3.6 vs 6.7+/-1.8, p=<0.0001), higher ejection fraction, (65+/-6 vs 59+/-6%, p=0.03), elevated resting BNP (11.4+/-6.5 vs 7.4+/-4.0 pmol/L, p=0.03) and shorter exercise duration (8.2+/-3.0 min vs 10.9+/-2.6 min, p=0.002). AS patients with an increase in systolic BP of 20 mmHg (13.8+/-6.1 vs 8.6+/-6.0 pmol/L, p=0.003). The BNP measured at peak exercise was also associated with the BP response (p=0.003). The area under the receiver operator curve to predict an abnormal BP response to exercise was 0.82 for BNP measured at rest but only 0.46 for aortic valve area. There was a modest association between raised BNP and lower exercise capacity.. In patients with AS there is an association between BNP and an abnormal BP response to exercise. Further study is needed to determine the incremental prognostic value of BNP and exercise testing in asymptomatic AS.

Topics: Aged; Aortic Valve Stenosis; Blood Pressure; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain

To determine whether longitudinal left ventricular systolic function measured by Doppler tissue imaging (DTI) after exercise can identify early left ventricular dysfunction in asymptomatic patients with moderate-severe aortic stenosis.. Case-control study.. Outpatient cardiology departments.. 20 patients with aortic stenosis, with or without equivocal symptoms, a peak aortic valve velocity > or =3 m/s, and left ventricular ejection fraction >50% and 15 aged-matched normal controls.. Echocardiogram performed at rest and immediately after treadmill exercise.. The peak systolic velocity of the lateral mitral annulus (S') by DTI at rest and immediately after exercise, exercise capacity, exercise systolic blood pressure and the plasma level of B-type natriuretic peptide (BNP).. For patients with aortic stenosis, mean (SD) aortic valve area was 0.95 (0.3) cm(2). At rest, S' was similar for patients with aortic stenosis and controls, respectively (8.5 (1.5) vs 9.1 (1.8) cm/s, p = 0.15). However, after exercise, S' (12.2 (3.2) vs 17 (2.8) cm/s, p<0.001) and the increase in S' between rest and exercise (4 (3) vs 7.9 (1.5) cm/s, p<0.001) were lower in patients with aortic stenosis. In patients with aortic stenosis, a smaller increase in S' after exercise was associated with lower exercise capacity (r = 0.5, p = 0.02), a smaller increase in exercise systolic blood pressure (r = 0.6, p = 0.005) and higher plasma level of BNP (r = 0.66, p = 0.002).. In asymptomatic patients with moderate-severe aortic stenosis a lower than normal increase in peak systolic mitral annular velocity after treadmill exercise is a marker of early left ventricular systolic dysfunction.

Topics: Aged; Aortic Valve Stenosis; Blood Pressure; Case-Control Studies; Echocardiography, Doppler; Exercise; Exercise Tolerance; Female; Humans; Male; Mitral Valve; Multivariate Analysis; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left

In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and its precursor, the amino-terminal pro-hormone (NT-proBNP) are independent predictors of outcome. Deterioration of cardiac function in AS is currently assessed by symptomatology and echocardiography to determine the optimal time point for surgery. We investigated whether BNP or NT-proBNP may help to estimate the individual risk of patients for subendocardial ischaemia in patients with moderate and severe AS.. In 71 patients with AS and 24 controls, the association of plasma natriuretic peptides with invasively measured haemodynamic parameters, including the myocardial oxygen supply-to-demand ratio [diastolic pressure time index/systolic pressure time index (DPTI/SPTI)] was cross-sectionally assessed.. Levels of natriuretic peptides increased with severity of AS. In patients with moderate AS (n = 30), natriuretic peptides differentiated between symptomatic and asymptomatic status (P = 0.01). BNP and NT-proBNP values correlated negatively with DPTI/SPTI (r = -0.58 and -0.51, P < 0.001, respectively) and left ventricular (LV) ejection fraction (EF) (r = -0.52 and -0.59, P < 0.001, respectively). DPTI/SPTI correlated with aortic valve area (P < 0.0001) but not with EF. Receiver operating characteristic analysis determined cut-off values of > 450 pg mL(-1) for BNP and of > 1800 pg mL(-1) for NT-proBNP for those AS patients who were at highest risk for subendocardial ischaemia (i.e. DPTI/SPTI < 0.22) in combination with impaired LV systolic function (i.e. EF < 45%).. Elevated natriuretic peptides show cardiac deterioration in AS and may help to identify those patients in need for early valve replacement.

Topics: Adult; Aged; Aortic Valve Stenosis; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Oxygen

B-type natriuretic peptide (BNP) is synthesized in cardiac tissue in response to increased wall stress and myocardial hypertrophy.. In patients with severe aortic stenosis (AS) we examined the effect of aortic valve replacement (AVR) on plasma BNP and association between BNP and left ventricular mass index (LVMI) preoperatively and in the reverse-remodeling phase twelve months postoperatively. We also examined the correlation between BNP and NYHA-class and between BNP and age.. Plasma BNP analyses and echocardiographic measurements were performed preoperatively, before discharge after AVR, and at twelve months in twenty-two patients. BNP was additionally measured at six months. Preoperatively, BNP was 283+/-45 pg/ml (mean+/-SEM). Following an immediate postoperative increase (441+/-38 pg/ml), BNP values decreased towards normal values at six and twelve months (139+/-25 and 130+/-18 pg/ml, respectively). LVMI was 206.5+/-15.8 g/m(2) preoperatively and decreased to 119.7+/-7.2 g/m(2) at twelve months with a correlation between LVMI and BNP preoperatively only (r=0.45, p<0.05). There was no correlation between BNP and NYHA-class, whereas BNP correlated to age both pre- and post-operatively.. We report an increase in plasma BNP in patients with AS. Following a further transient increase postoperatively, BNP levels decreased at six and twelve months after AVR. BNP correlated with LVMI preoperatively, and with age both preoperatively and at twelve months.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Female; Follow-Up Studies; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain

Demonstration that aldosterone synthesis occurs in the myocardium would suggest that the clinical benefits of aldosterone receptor antagonists may extend to patients with normal circulating plasma levels of aldosterone. Previous studies have reported myocardial aldosterone synthesis in patients with heart failure. This study determined whether myocardial aldosterone and angiotensin II release occurs in patients with aortic stenosis (AS) and/or coronary heart disease (CHD) with normal left ventricular ejection fractions and no clinical heart failure. In 19 patients with severe AS and 18 patients with stable CHD, plasma levels of aldosterone, angiotensin II, B-type natriuretic peptide (BNP), and procollagen type III amino terminal peptide (PIIINP) were measured in blood samples taken from the coronary sinus and aortic root before diagnostic coronary angiography. Plasma aldosterone was approximately 20% greater in the coronary sinus than the aorta, respectively, in the 2 patient groups (AS: 120 vs 102 pmol/L, p <0.001; CHD: 94 vs 77 pmol/L, p <0.001). Plasma angiotensin II was also greater in the coronary sinus (AS: 16 vs 11 pmol/L, p <0.001; CHD: 12 vs 9 pmol/L, p <0.001). Plasma levels of BNP in the coronary sinus were approximately double those in the aorta in the 2 groups of patients (p <0.001). In contrast, there was no transmyocardial gradient in the plasma level of PIIINP for either AS or CHD. In conclusion, these results indicate that aldosterone, angiotensin II, and BNP are released into the coronary sinus in severe AS and in stable CHD, even when the left ventricular ejection fraction is normal and there is no clinical heart failure.

Topics: Aged; Aldosterone; Angiotensin II; Aorta; Aortic Valve Stenosis; Coronary Disease; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Stroke Volume; Venae Cavae

To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with aortic stenosis being treated conservatively or undergoing aortic valve replacement (AVR).. 159 patients were followed up for a median of 902 days. 102 patients underwent AVR and 57 were treated conservatively. NT-proBNP at baseline was raised in association with the degree of severity and of functional status.. During follow up 21 patients (13%) died of cardiac causes or required rehospitalisation for decompensated heart failure. NT-proBNP at baseline was higher in patients with an adverse outcome than in event-free survivors (median 623 (interquartile range 204-1854) pg/ml v 1054 (687-2960) pg/ml, p = 0.028). This difference was even more obvious in conservatively treated patients (331 (129-881) pg/ml v 1102 (796-2960) pg/ml, p = 0.002). Baseline NT-proBNP independently predicted an adverse outcome in the entire study group and in particular in conservatively treated patients (area under the curve (AUC) = 0.65, p = 0.028 and AUC = 0.82, p = 0.002, respectively) but not in patients undergoing AVR (AUC = 0.544). At a cut-off value of 640 pg/ml, baseline NT-proBNP was discriminative for an adverse outcome.. NT-proBNP concentration is related to severity of aortic stenosis and provides independent prognostic information for an adverse outcome. However, this predictive value is limited to conservatively treated patients. Thus, the data suggest that assessing NT-proBNP may have incremental value for selecting the optimal timing of valve replacement.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Disease-Free Survival; Echocardiography; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Recurrence; Sensitivity and Specificity; Treatment Outcome

Topics: Animals; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Clinical Trials as Topic; Disease Models, Animal; Echocardiography; Female; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Time Factors; Tomography, X-Ray Computed

While there is generell agreement that patients with aortic stenosis (AS) who have already developed symptoms, such as exertional dyspnea, angina or dizziness and syncope, require urgent surgery because of their otherwise very poor outcome, the management of asymptomatic severe AS remains controversial. Although prevention of sudden death, prevention of irreversible myocardial damage, lower operative risk and a possible short duration of the asymptomatic phase of the disease have been proposed as arguments for early elective surgery, currently available data do not support that the risk of surgery and prosthesis-related long-term complications can generally be outweighed by a potential benefit. Thus, surgery cannot be recommended for all asymptomatic patients. Since patients often do not report their symptoms immediately and waiting lists for surgery exist in some countries, risk stratification with selection of those patients who are likely to develop symptoms and require surgery within a short time period seems to be the ideal approach. The most important predictors of outcome are the degree of valvular calcification, the hemodynamic progression rate, the development of symptoms during exercise testing, and plasma levels of cardiac neurohomones.

Topics: Age Factors; Aged; Aortic Valve Stenosis; Calcinosis; Clinical Trials as Topic; Death, Sudden, Cardiac; Disease Progression; Echocardiography; Exercise; Exercise Test; Follow-Up Studies; Humans; Natriuretic Peptide, Brain; Patient Selection; Prognosis; Risk Assessment; Risk Factors; Time Factors

The pregnancy hormone relaxin has been raised as a new compensatory mediator of cardiac origin in heart failure (HF). We set out to assess the role of relaxin in pressure overload-induced human HF.. We studied 129 adult patients undergoing cardiac catheterization for isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 49 patients, from the coronary sinus for the determination of plasma relaxin by enzyme immunoassay. HF was diagnosed when the patient had dyspnea or fatigue on ordinary effort in association with pulmonary wedge pressure >14 mm Hg at catheterization.. Forty-one patients had HF, which was systolic (ejection fraction <50%) in 16 patients and diastolic in 25 patients. The median plasma relaxin was 32 pg/ml (<12-297 pg/ml) in 88 AS patients without HF, 28 pg/ml (<12-825 pg/ml) in the 41 AS patients with HF, and 42 pg/ml (range, <12-100 pg/ml) in 11 control patients free of heart disease (p=0.82). Plasma relaxin did not correlate with any measurement of cardiac structure or function. The concentration gradients of relaxin from the aortic root to the coronary sinus indicated relaxin extraction by the heart in the control patients (median change, -5 pg/ml, p=0.038) vs. relaxin production in patients with systolic HF (median change, +6 pg/ml, p=0.028) (p=0.002 between groups).. Although the heart may release relaxin into the circulation in certain forms of HF, this does not translate into elevated systemic concentrations. Relaxin is not a major player in human HF.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Cardiac Catheterization; Cardiac Output, Low; Case-Control Studies; Endothelin-1; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Relaxin

In 29 initially asymptomatic patients with aortic stenosis followed for an average of 18 months, patients with a N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level above the normal range at baseline were more likely to develop symptoms during follow-up compared with patients with NT-pro-BNP within normal limits. The average increase in NT-pro-BNP per year was greater for patients who developed symptoms compared with patients who remained asymptomatic. Aortic valve area, peak aortic velocity, and the ejection fraction were less reliable predictors of symptom onset. Measurement of NT-pro-BNP in addition to clinical assessment and echocardiography may allow more reliable follow-up and timing of valve replacement for aortic stenosis.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Disease Progression; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests

Recently an elevation of B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) in patients with aortic stenosis (AS) and aortic regurgitation (AR) has been described. The objective of this study was to evaluate the relation of NT-proBNP values to the progression of aortic valve disease.. One hundred and sixty-eight patients were included. NT-proBNP was elevated in patients with AS (n=109) and AR (n=37) linked to disease severity. Values for NT-proBNP, pressure gradient, and left ventricular mass were identical in patients (n=22) after previous valve replacement and in those patients with mild AS. NT-proBNP levels decreased in 86 patients after valve replacement (2292+/-353 vs. 785+/-101 pg/ml; P<0.01) but increased in 82 patients who were treated conservatively (616+/-120 vs. 1155+/-432 pg/mL; P=0.029), related to the progression of disease.. NT-proBNP is elevated in patients with aortic valve disease linked to disease severity and decreases after successful surgical therapy but increases in conservatively treated patients. These data underline the consistent relation of NT-proBNP to severity of aortic valve disease. Therefore, NT-proBNP should be considered as a biomarker for the monitoring of disease during follow-up, but further studies are warranted.

Topics: Aged; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Disease Progression; Echocardiography; Female; Heart Valve Prosthesis Implantation; Humans; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Prospective Studies

Topics: Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Humans; Natriuretic Peptide, Brain

Topics: Adolescent; Aortic Valve Stenosis; Biomarkers; Child; Humans; Natriuretic Peptide, Brain

Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS.. To assess the release of Nt-BNP in AS with focus on the identification of its main determinants.. We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay.. The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050).. LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.

Topics: Aged; Aortic Valve Stenosis; Cardiac Catheterization; Female; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography

Plasma natriuretic peptide type B (BNP) concentration increases in aortic stenosis (AS) but relation to severity of left ventricle hypertrophy (LVH) is unknown. We analyze the relation between BNP and the LVH (left ventricle mass index (LVMI)), left ventricle thickness (LVTh) in pts with significant aortic stenosis (AS).. 58 pts with AS (32 male), aged 62 +/- 12, underwent echocardiographic study before aortic valve replacement. BNP level was measured using SHIONORIA BNP test (immunoradiometric method). Results were expressed as a mean (+/- standard deviation). Control group consisted of 26 healthy people. Correlation between BNP level and age, gender, EF, MGA and LVH were also tested.. In pts with AS BNP level ranged from 11 to 2010 pg/ml. Mean BNP level was similar in men and women (mean level in whole group 344 +/- 480 pg/ml) and it was higher than in control group (6,1 +/- 3,9 pg/ml). BNP level was related with LVMI (r = 0,42; p<0,001), LVDD (r=0,61; p<0,0001), EF (r = -0,66; p<0,0001 - higher BNP level in lower EF) but not with LVTh (r = -0,08; p = ns), age (r = 0,06; p = ns) and MGA (r = -0,19; p = ns). BNP in 11 pts in eccentric type of hypertrophy was significantly higher (721 +/- 773 pg/ml) then in 47 cases with concentric type of remodeling (256 +/- 337; p = 0,04).. 1. BNP level increased in relation to left ventricle mass index (increase in left ventricle diastolic diameter) but not to wall thickness 2. BNP measurement could potentially be used to monitor left ventricle remodeling in aortic stenosis.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Case-Control Studies; Female; Humans; Hypertrophy, Left Ventricular; Immunoradiometric Assay; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index; Ventricular Remodeling

Patients with aortic stenosis (AS) may remain asymptomatic with good prognoses for many years but have poor prognoses once they develop symptoms. Because the presence of symptoms is subjective, B-type natriuretic peptide (BNP) may provide a more objective indication of the prognoses of patients with AS. We evaluated 124 patients with AS (valve area <1.2 cm(2)) with clinical evaluation, Doppler echocardiography, and BNP assessment and obtained up to 2 years of follow-up without valve replacement. Patients with syncope, angina, and/or heart failure were considered to have symptoms. The 24 patients without symptoms had lower BNP levels (187 +/- 193 pg/ml) than the 100 patients with symptoms (930 +/- 928 pg/ml, p <0.001). BNP indicated symptom status, with an area under the receiver-operating characteristic curve of 0.87 (p <0.001). The optimal discrimination of symptoms occurred with BNP >190 pg/ml. Survival was significantly influenced by the presence of symptoms (relative risk [RR] 7.5, p <0.01) and BNP tertile (RR 2.9, p <0.001). The 1-year mortality rate without surgery was 6% for BNP <296 pg/ml, 34% for BNP 296 to 819 pg/ml, and 60% for BNP >819 pg/ml. No patients with BNP <100 pg/ml died. The combination of BNP and symptoms provided a better prediction of survival than symptoms alone (chi-square 13.6, p <0.001). BNP significantly (RR 2.8, p <0.01) influenced survival after correction for other univariate predictors (coronary artery disease, symptoms, functional class, ejection fraction, and aortic valve area). In conclusion, elevated BNP indicates progressively worse survival in patients with AS treated medically. Thus, the measurement of BNP supplements the evaluation of symptoms in determining the prognoses of patients with AS.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Coronary Artery Disease; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Stroke Volume; Survival Analysis; Treatment Outcome

The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown.. B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70+/-12 years; mean gradient, 64+/-21 mm Hg; valve area, 0.64+/-0.15 cm2) who were followed up for 377+/-150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L]; P<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus > or =80 pmol/L was 100%, 88+/-7%, 88+/-7%, and 69+/-13% compared with 92+/-8%, 58+/-14%, 35+/-15%, and 18+/-15%, respectively (P<0.001). Seventy-nine patients eventually underwent surgery because of symptoms. Considering preoperative neurohormone levels, age, NYHA class, aortic valve area, EF, and presence of coronary artery disease, we found that neurohormones, EF, and NYHA class predicted survival; neurohormones predicted postoperative symptomatic status; and neurohormones and preoperative EF predicted postoperative EF. However, by multivariate analysis, NtBNP was the only independent predictor of outcome.. In severe AS, natriuretic peptides provide important prognostic information beyond clinical and echocardiographic evaluation. NtBNP independently predicts symptom-free survival, and preoperative NtBNP independently predicts postoperative outcome with regard to survival, symptomatic status, and left ventricular function. Thus, neurohormones may gain particular importance for timing of surgery in asymptomatic severe AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Atrial Natriuretic Factor; Biomarkers; Disease Progression; Disease-Free Survival; Dyspnea; Female; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Life Tables; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Severity of Illness Index; Single-Blind Method; Stroke Volume; Treatment Outcome; Ultrasonography

The aim of our study was to investigate the ability of BNP levels to reveal the immediate post-surgery cardiac function improvement. We measured the perioperative variations in BNP concentrations in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB), chronic mitral regurgitation, valvular aortic stenosis, or myocardial ischaemia.. Three groups were included: patients with coronary artery bypass graft (CABG, group I, n = 14), aortic (AVR, group II, n = 14) or mitral (MVR, group III, n = 7) valve replacement. BNP assay was performed at the induction of anesthesia, immediately after the CPB, at the arrival in the intensive care unit, 4 h, 8 h and 12 h after the arrival in ICU.. The occurring variation in BNP levels after the operation is an increase whatever the corrective surgery, underlying the relative lack of specificity of BNP with regard to the cardiac pathology. Besides iatrogenic cardioplegia one can supposes that cardiac surgery involves other major stimuli such as anesthesia, sternotomia, hemodynamics, post-operative that could influence in a non specific way BNP levels.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Cardiopulmonary Bypass; Coronary Artery Bypass; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Postoperative Period; Prospective Studies

The endoplasmic reticulum (ER) is recognized as an organelle that participates in folding secretory and membrane proteins. The ER responds to stress by upregulating ER chaperones, but prolonged and/or excess ER stress leads to apoptosis. However, the potential role of ER stress in pathophysiological hearts remains unclear.. Mice were subjected to transverse aortic constriction (TAC) or sham operation. Echocardiographic analysis demonstrated that mice 1 and 4 weeks after TAC had cardiac hypertrophy and failure, respectively. Cardiac expression of ER chaperones was significantly increased 1 and 4 weeks after TAC, indicating that pressure overload by TAC induced prolonged ER stress. In addition, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells increased, and caspase-3 was cleaved in failing hearts. The antagonism of angiotensin II type 1 receptor prevented upregulation of ER chaperones and apoptosis in failing hearts. On the other hand, angiotensin II upregulated ER chaperones and induced apoptosis in cultured adult rat cardiac myocytes. We also investigated possible signaling pathways for ER-initiated apoptosis. The CHOP- (a transcription factor induced by ER stress), but not JNK- or caspase-12-, dependent pathway was activated in failing hearts by TAC. Pharmacological ER stress inducers upregulated ER chaperones and induced apoptosis in cultured cardiac myocytes. Finally, mRNA levels of ER chaperones were markedly increased in failing hearts of patients with elevated brain natriuretic peptide levels.. These findings suggest that pressure overload by TAC induces prolonged ER stress, which may contribute to cardiac myocyte apoptosis during progression from cardiac hypertrophy to failure.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Aortic Valve Stenosis; Apoptosis; Cardiomegaly; Cells, Cultured; Disease Models, Animal; Disease Progression; Endoplasmic Reticulum; Gene Expression Regulation; Heart Failure; Humans; Imidazoles; Ligation; Male; Mice; Mice, Inbred C57BL; Molecular Chaperones; Myocytes, Cardiac; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Rats; Rats, Inbred WKY; RNA, Messenger; Signal Transduction; Stress, Physiological; Tetrazoles; Thapsigargin; Tunicamycin

N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been shown to be a reliable biochemical marker for left ventricular wall stress and is increased in patients with aortic stenosis (AS). We evaluated the role of NT pro-BNP as a biochemical marker in the diagnosis of AS and whether it contributes to the optimal timing for aortic valve replacement (AVR). Included in this study were 146 patients who had AS, 31 who underwent AVR, and 32 who had "normal valve function" (controls). Increased NT pro-BNP was closely linked to severity of AS (mild AS 612 +/- 151 pg/ml, moderate AS 1,441 +/- 32 pg/ml, severe AS 2,579 +/- 13 pg/ml, AVR 593 +/- 148 pg/ml, controls 140 +/- 27 pg/ml; p <0,01) and to New York Heart Association functional class (class I 601 +/- 116 pg/ml, class II 1,119 +/- 216 pg/ml, class III 1,998 +/- 459 pg/ml, class IV 5,107 +/- 1,512 pg/ml; p <0.01). Area under the receiver-operating characteristic curve for NT pro-BNP as a predictor for AVR was 0.73. Using an optimized cutoff of 550 pg/ml for NT-proBNP, the positive predictive value was 85%. Thus, NT pro-BNP is linked to severity of AS and New York Heart Association class and is an indication for AVR. Therefore, it is a useful biochemical marker to evaluate severity of AS, monitor disease progression at an early stage, and decide on the optimal time for AVR.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; Data Interpretation, Statistical; Echocardiography; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prospective Studies; Severity of Illness Index

In aortic valve stenosis (AS), heart failure (HF) omens a high risk of death and is an indication for prompt valve replacement. We studied whether its detection can be facilitated by measuring plasma N-terminal B-type natriuretic peptide (Nt-BNP) or by estimating pulmonary capillary wedge pressure (PCWP) using echocardiography.. A cross-sectional cohort study in a university hospital.. We studied 137 consecutive adult patients referred to our unit for invasive evaluation of isolated AS. All patients underwent cardiac catheterization, measurement of plasma Nt-BNP and estimation of PCWP by Doppler echocardiography of transmitral and pulmonary venous flow velocities. The final diagnosis of HF was based on the combined criteria of dyspnoea on ordinary effort and PCWP >14 mmHg at cardiac catheterization. The performance of Nt-BNP and the PCWP estimate in the detection of HF were studied using receiver operating characteristic (ROC) analysis.. Totally 42 patients had HF. A cardiologist's clinical diagnosis of HF had high specificity (94%) but poor sensitivity (66%). With an optimized cut-off point, plasma Nt-BNP had moderate sensitivity (77%) and specificity (79%) for HF; the ROC area was 0.83. The echocardiographic PCWP estimate classified 90% of patients correctly as having normal or truly elevated (>14 mmHg) PCWP. Its sensitivity and specificity for the diagnosis of HF were 80 and 95% respectively; the ROC area was 0.88. With a cut-off point of 12 mmHg, the sensitivity of the PCWP estimate was 85% and specificity, 88%.. The recognition of HF in patients with AS can be improved by estimating PCWP using Doppler echocardiography of transmitral and pulmonary venous flow velocities.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Cohort Studies; Cross-Sectional Studies; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain

Estrogen receptor (ER)-mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but ER expression in the human heart and its relation to hypertrophy-mediated gene expression have not yet been analyzed. We therefore investigated sex- and disease-dependent alterations of myocardial ER expression in human aortic stenosis together with the expression of hypertrophy-related genes.. ER-alpha and -beta, calcineurin A-beta, and brain natriuretic peptide (BNP) mRNA were quantified by real-time polymerase chain reaction in left ventricular biopsies from patients with aortic valve stenosis (n=14) and control hearts with normal systolic function (n=17). ER protein was quantified by immunoblotting and visualized by immunofluorescence confocal microscopy. ER-alpha mRNA and protein were increased 2.6-fold (P=0.003) and 1.7-fold (P=0.026), respectively, in patients with aortic valve stenosis. Left ventricular ER-beta mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-alpha and -beta were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-beta and calcineurin A-beta mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER-alpha or -beta and BNP mRNA.. ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Aortic Valve Stenosis; Calcineurin; Cell Nucleus; Cytoplasm; Diuretics; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation; Heart Ventricles; Hormone Replacement Therapy; Humans; Male; Microscopy, Fluorescence; Middle Aged; Natriuretic Peptide, Brain; Pressure; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

Topics: Aortic Valve Stenosis; Humans; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Survival Analysis

B-type Natriuretic Peptide (BNP) is activated in patients with severe, symptomatic aortic stenosis (AS), but the prognostic value of BNP in this setting has not been extensively studied. This study aimed to assess the prognostic value of the BNP level in symptomatic and asymptomatic patients with severe AS.. Seventy consecutive patients referred to our echocardiography laboratory for severe AS with preserved left ventricular function were prospectively enrolled (40 men, median age 74 years [62-82]; aortic valve area 0.7 cm2 [0.6-0.8]; transaortic gradient 48 mmHg [38-60], and left ventricular fractional shortening 38% [32-43]). C-terminal BNP serum level at enrollment was evaluated against baseline functional and echocardiographic parameters as well as clinical outcome.. BNP level was elevated in the presence of symptoms and increased with NYHA functional class. BNP serum level >66 pg/ml detected symptomatic patients with a sensitivity, specificity and accuracy of 84%, 82% and 84%, respectively. In symptomatic and asymptomatic patients, BNP level was a strong independent predictor for cardiovascular death by multivariable analysis adjusted to age and NYHA functional class.. BNP serum level allows to differentiate symptomatic from asymptomatic patients with severe AS. BNP is an independent predictor of outcome in these patients and may be helpful for risk stratification.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Survival Analysis; Ventricular Dysfunction, Left; Ventricular Function, Left

Brain natriuretic peptide (BNP) is a cardiac hormone secreted from the ventricular myocardium as a response to ventricular volume expansion and pressure overload. Rheumatic heart disease (RHD) is still an important cause of heart failure in developing countries.. To measure BNP levels in patients with RHD and to determine whether BNP concentrations correlate with clinical and echocardiographic findings.. Eighty-eight patients with rheumatic valve disease and 24 age- and sex-matched healthy subjects were entered in the study. BNP was measured using the Triage B-Type Natriuretic Peptide test (Biosite Diagnostics, San Diego, CA). Transthoracic echocardiography was performed in all patients to assess the severity of the valve disease and for the measurement of pulmonary artery pressure.. The plasma concentrations of BNP were significantly higher in patients with rheumatic heart disease than in control subjects (232+/-294 vs. 14+/-12 pg/ml, p<0.0001). The plasma BNP level was significantly higher in NYHA class III+IV than in class II (463+/-399 vs. 192+/-243 pg/ml, p<0.0001) and in NYHA class II than in class I (192+/-243 vs. 112+/-135 pg/ml, p<0.001). The independent determinants of higher BNP levels were NYHA functional class and systolic pulmonary artery pressure in multivariate analysis.. We found increased plasma BNP levels in patients with rheumatic heart disease compared with healthy subjects.

Topics: Adult; Aortic Valve Stenosis; Cross-Sectional Studies; Echocardiography, Doppler; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Rheumatic Heart Disease; Tricuspid Valve Stenosis

We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure.. In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial.. In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California).. A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011).. In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Diastole; Echocardiography; Female; Follow-Up Studies; Heart; Hemodynamics; Humans; Hypertension; Inpatients; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Stress, Mechanical; Stroke Volume; Systole; Ventricular Function, Left

The onset of symptoms is a critical point in the natural history of aortic stenosis and the cardinal indication for valve replacement. This study assessed the associations between natriuretic peptide levels, disease severity, and cardiac symptoms in aortic stenosis.. Seventy-four patients with isolated aortic stenosis underwent independent assessment of symptoms, transthoracic echocardiography, and measurement of plasma levels of atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-BNP. Natriuretic peptide levels were also measured in 100 clinically normal control subjects. The aortic valve area was smaller in symptomatic patients (n=45) than in asymptomatic patients (n=29; mean, 0.71+/-0.23 cm2 and 0.99+/-0.31 cm2, respectively; P<0.0001). Plasma natriuretic peptide levels were higher in symptomatic patients than in asymptomatic patients (for N-BNP: median, 112 versus 33 pmol/L; interquartile range, 70 to 193 versus 16 to 58 pmol/L, respectively; P=0.0002). After adjustment for age, sex, serum creatinine, aortic valve area, and left ventricular ejection fraction, N-BNP levels were 1.74 times higher (95% confidence interval, 1.12 to 2.69) for symptomatic than asymptomatic patients with aortic stenosis (P=0.014). Natriuretic peptide levels increased with the New York Heart Association class (for N-BNP median values were 13, 34, 105, and 202 pmol/L for normal control subjects, class I, class II, and class III/IV patients, respectively; interquartile ranges for the same patients were 8 to 21, 16 to 58, 57 to 159, and 87 to 394 pmol/L; P<0.0001). Similar associations were observed for BNP and atrial natriuretic peptide.. Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic stenosis. Measurement of natriuretic peptides may complement clinical and echocardiographic evaluation of patients with aortic stenosis.

Topics: Age Factors; Angina Pectoris; Aortic Valve Stenosis; Atrial Natriuretic Factor; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; ROC Curve; Sensitivity and Specificity; Sex Factors; Syncope

The study aim was to evaluate the relationship between plasma concentrations of brain natriuretic peptide (BNP) and the type or degree of stenosis in the left ventricular outflow tract (LVOT).. The relationship between BNP plasma level and pressure gradient (PG) in the LVOT and LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled ventricular septum. Three patients with AS showed LV systolic dysfunction (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak-systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic arterial pressure.. In AS patients without LV systolic dysfunction and HOCM patients, there was a significant positive correlation between BNP and LVPSP (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p = 0.001), but no correlation was found between BNP and LVWth in patients with HOCM. In AS patients including systolic LV dysfunction, BNP was negatively correlated with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and LVEF in patients with HOCM.. These results suggest that BNP level is closely associated with severity of stenosis in patients with HOCM, but mainly with severity of stenosis and also degree of LV systolic dysfunction in patients with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with uneven myocardial hypertrophy).

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Biomarkers; Cohort Studies; Echocardiography, Doppler; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Probability; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Ventricular Function, Left; Ventricular Outflow Obstruction; Ventricular Pressure

Increased plasma concentrations of natriuretic peptides have been demonstrated to be associated with increased intracardiac pressure and left ventricular (LV) hypertrophy. After aortic valve replacement (AVR) in aortic stenosis patients, there is a relief of the left outflow obstruction with a substantial hemodynamic improvement. This is followed by a gradual regression of the LV hypertrophy.. After AVR, reduction in LV filling pressure is expected to occur rapidly, while regression of LV hypertrophy will take place over a longer time period. On this basis we hypothesized that the plasma levels of N-terminal proatrial natriuretic peptide (NT-proANP) would be reduced early in the postoperative period, while N-terminal probrain natriuretic peptide (NT-proBNP), through its closer reflection of LV hypertrophy, would be sustained for a longer period.. Two groups of patients with aortic stenosis undergoing AVR were followed for 4 and 12 months, respectively. Plasma concentrations of NT-proANP and NT-proBNP were measured before and after AVR and related to preoperative findings and changes in the aortic valve area index.. Before AVR, the patients had significantly increased plasma levels of NT-proANP and NT-proBNP. After AVR, NT- proANP was decreased at 4 and 12 months but remained elevated compared with controls. N-terminal-proBNP tended to decrease, but did not change significantly. When the patients were followed for 12 months, only those with elevated preoperative pulmonary capillary wedge pressure had decreased peptide levels (NT-proANP: p = 0.017, NT-proBNP: p = 0.058). There was no regression of LV hypertrophy. The patients with the largest postoperative valve area index [1.27 (1.10-1.55) cm2/m2] had the largest reduction of NT-proBNP (47%). Those with the smallest valve area index [0.67 (0.54-0.73) cm2/m2] had no decrease in NT-proBNP.. Our study suggests that a reduction in left atrial pressure is the main factor causing the change of NT-proANP level after AVR. A small prosthetic valve orifice area with a high aortic valve gradient might prevent regression of LV hypertrophy, thus representing a stimulus for increased cardiac secretion of NT-proBNP.

Topics: Aged; Aortic Valve Stenosis; Atrial Natriuretic Factor; Female; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Protein Precursors; Pulmonary Wedge Pressure; Ventricular Pressure

Echocardiography with Doppler examination of the aortic valve provides a very accurate assessment of the transvalvular gradient and is used to monitor progression of aortic stenosis (AS). Plasma brain natriuretic peptide (BNP) has been shown to correlate with end-systolic wall stress in patients with AS.. We hypothesized that plasma N-terminal proBNP (NT proBNP) and a newly identified cytokine cardiotrophin-1 (CT-1), which has been shown to stimulate BNP production at a transcriptional level are elevated in patients with AS and correlate to the maximum trans-valvular aortic pressure gradient (TVPG).. We compared plasma NT proBNP and CT-1 in 15 AS patients [five males, mean age 79 years [range 60-94], mean TPVG 39.3 mmHg (20-100)] with 10 controls (five male, mean age 68 years [56-79]). Results are expressed as mean [ranges] and comparisons were by the Mann-Whitney test.. NT proBNP levels were elevated in AS patients [252.9 fmol/ml (79.2-541.8)] when compared with the controls (157.2 fmol/ml [104.7-236.9], P<0.005). Also CT-1 levels were elevated in AS patients (57.3 fmol/ml [33-86.3] when compared with the controls [28.3 fmol/ml (6.9-48.3), P<0.0005]. Both NT proBNP and CT-1 levels were correlated to the TVPG (r=0.53 and r=0.65, P<0.05 and P=0.009, respectively). On best subset analysis the strongest correlate with TVPG was CT-1 (R2=38%). The addition of NT proBNP did not improve diagnostic accuracy (R2=39%).. These results suggest NT proBNP and CT-1 levels increase in proportion to the TVPG and could potentially be used to monitor progression of disease non-invasively. These markers may also be useful to identify the optimum time for surgery in AS.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Case-Control Studies; Cytokines; Echocardiography, Doppler; Female; Humans; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Statistics, Nonparametric

Whereas atrial natriuretic peptide (ANP) is secreted mainly from cardiac atria, brain natriuretic peptide (BNP) is produced to a larger extent in ventricles. Their relative importance as markers of cardiac function and myocardial hypertrophy is not yet clarified. This study evaluated circulating BNP and ANP and the N-terminal part of their propeptides (NT-proBNP and NT-proANP) as markers of left ventricular hypertrophy and atrial pressure increase in patients with aortic stenosis.. The plasma concentrations of BNP, NT-proBNP, ANP, and NT-proANP were measured by radioimmunoassay in 67 patients with aortic stenosis. Peptide plasma concentrations were related to measurements obtained by cardiac catheterization and echocardiography.. Receiver operating characteristic curves indicated that BNP and NT-proBNP performed best in the detection of increased left ventricular mass and NT-proANP in the detection of increased left atrial pressure. NT-proBNP was significantly increased in mild left ventricular hypertrophy (left ventricular mass index, 78 to 139 g/m(2)), whereas NT-proANP was not increased until left ventricular mass index was 141 to 180 g/m(2).. Plasma BNP and NT-proBNP may serve as early markers of left ventricular hypertrophy, whereas ANP and NT-proANP reflect left atrial pressure increase. The repeated and combined measurements of natriuretic peptides might provide diagnostic information relevant to the evaluation of the stage of aortic stenosis.

Topics: Adult; Aged; Aortic Valve Stenosis; Atrial Function, Left; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; ROC Curve

Brain natriuretic peptide (BNP) is a novel cardiac hormone secreted predominantly from the ventricle. We examined the plasma levels of BNP and atrial natriuretic peptide (ANP) in 13 patients with aortic stenosis undergoing corrective surgery. Preoperative plasma BNP and ANP levels correlated highly with preoperative left ventricular end-systolic wall stress (ESS) (r = 0.96, p < 0.0001 and r = 0.95, p < 0.0001, respectively). Moreover, between preoperative and late postoperative states, the difference of the plasma levels of BNP and ANP correlated with the difference of ESS. In two patients with elevated ESS and quite high preoperative plasma BNP (> 1000 pg/ml), rapid decrease of the plasma level after operation was observed. These results suggest that synthesis and secretion of BNP and ANP are stimulated by the increase of left ventricular end-systolic wall stress in patients with aortic stenosis.

Topics: Aged; Aortic Valve Stenosis; Atrial Natriuretic Factor; Echocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Postoperative Period; Systole; Ventricular Function, Left

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Atrial Natriuretic Factor; Cardiac Catheterization; Case-Control Studies; Echocardiography, Doppler; Female; Heart Valve Prosthesis; Humans; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Predictive Value of Tests