natriuretic-peptide--brain and Aortic-Valve-Insufficiency

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

Topics: Aortic Valve Insufficiency; Humans; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Chronic aortic regurgitation (AR) creates a volume load on the left ventricle, which induces adaptive responses. With time, excessive left ventricular (LV) dilatation may precipitate heart failure. β-adrenergic receptor antagonists (β-blockers) are beneficial in patients with heart failure, but their effect in AR is unclear. This trial was designed to evaluate the effect of controlled release metoprolol on LV remodelling in patients with AR.. In this double blind trial, 75 asymptomatic patients aged 44±14 years, 89% males, fulfilling at least two echocardiographic criteria for moderate or severe chronic AR, were randomised to receive metoprolol CR/XL up-titrated to 200 mg/day, or matching placebo. The primary endpoint was LV end diastolic volume, measured by MRI after 6 months of treatment.. After 6 months, the difference in the baseline-adjusted LV end diastolic volume between patients allocated to metoprolol and those allocated to placebo was 8 (95% CI -8 to 25) mL (p=0.32). The adjusted LV ejection fraction was 2.7 (95% CI 0.1 to 5.3) percentage points higher in the metoprolol group than in the placebo group (p=0.04). The exercise capacity and peak oxygen consumption did not differ between treatment arms. Serum concentrations of N-terminal pro-B-type natriuretic peptide were 138 (95% CI 71 to 205) pg/mL higher in the metoprolol group (p<0.001). There were no serious adverse events in either treatment arm.. Treatment with metoprolol of adults with chronic, moderate to severe AR had no effect on LV volumes.. ClinicalTrials.gov Identifier: NCT01157572-results.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Aortic Valve Insufficiency; Asymptomatic Diseases; Delayed-Action Preparations; Double-Blind Method; Exercise Test; Female; Humans; Magnetic Resonance Imaging; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Severity of Illness Index; Treatment Outcome; Ventricular Remodeling

B-type natriuretic peptide is synthesized in response to increased ventricular wall stress (WS) and hypertrophy. To serially evaluate amino-terminal-pro-BNP (NT-pBNP) serum levels in patients undergoing aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR), blood samples were drawn preoperatively, 15 days postoperatively, at 6- and 12-month follow-up in 25 consecutive patients. Two-dimensional echocardiography was performed concomitantly, assessing left ventricular (LV) dimensional and functional parameters, including WS. Correlations between NT-pBNP, clinical and echocardiographic data were assessed by non-parametric statistics. Median preoperative NT-pro-BNP was 276 pg/ml (IQR=85-1056), being normal or mildly increased in 20 patients, overly increased in five. The most significant correlations of preoperative NT-pBNP were with diastolic (r=0.80, P<0.001) and systolic (r=0.75, P<0.001) meridional WS and inversely with time from symptom onset (r=-0.67, P=0.001). NT-pBNP increased 15 days postoperatively (568 pg/ml, P=0.006 vs. preoperative), then decreased at 6 months (144 pg/ml, P<0.001) to remain stable at 1 year (108 pg/ml, P=0.16). Long-term follow-up NT-pBNP showed direct correlation with diastolic WS (r=0.56, P=0.02). Higher preoperative levels of NT-pBNP predicted greater magnitude of total LV mass regression at follow-up (r=-0.65, P=0.002) independent of preoperative LV mass index, showing that NT-pBNP may have a potential prognostic usefulness in adjunct to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Predictive Value of Tests; Preoperative Care; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Function, Left; Ventricular Remodeling

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

Both N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and soluble isoform of ST2 (sST2) have been identified as biomarkers of heart failure. We evaluated the plasma levels of NT-proBNP and sST2 in a rat model of severe aortic valve regurgitation (AR) and correlated these findings with echocardiographic measurements. We also examined the impact of omecamtiv mecarbil (OM) on these parameters.. The plasma levels of NT-proBNP and sST2 were measured in 18 rats both before and 2 months after surgical induction of AR, and at these same time points, in six rats assigned to a sham-procedure control group. Plasma biomarkers were then measured again after infusion of OM or placebo in rats with AR (n=8 and 10, respectively) and OM alone in the sham control rats (n=6). Echocardiographic measurements were collected before and 2 months after induction of AR.. Our results revealed increased levels of plasma NT-proBNP (219 ± 34 pg/mL vs. 429 ± 374 pg/mL; p<0.001) in rats with AR at day 7 after infusion of placebo, whereas plasma levels of sST2 were higher in this cohort after infusion of either OM or placebo. We identified a significant positive correlation between plasma sST2 with posterior wall thickness in diastole (r=0.34, p<0.05) and total body weight (r=0.45, p<0.01) in rats with surgically induced AR.. Because sST2 increased markedly, whereas NT-proBNP remained unchanged, when OM was administered, we hypothesize that sST2 has a distinct capability to detect deleterious effects of passive muscle tension, not reliably assessed by NT-proBNP, in the setting of AR.

Topics: Animals; Aortic Valve Insufficiency; Biomarkers; Natriuretic Peptide, Brain; Rats

Use of the current echocardiography-based indications for aortic regurgitation (AR) surgery might result in late valve replacement at the stage of irreversible myocardial damage. Therefore, we aimed to identify simple models combining multiple echocardiography or magnetic resonance imaging (MRI)-derived indices and natriuretic peptides (BNP [brain natriuretic peptide] or NT-proBNP [N-terminnal pro-B type natriuretic peptide]) to predict early disease decompensation in asymptomatic severe AR.. This prospective and multicenter study included asymptomatic patients with severe AR, preserved left ventricular ejection fraction (>50%), and sinus rhythm. The echocardiography and MRI images were analyzed centrally in the CoreLab. The study end point was the onset of indication for aortic valve surgery as per current guidelines.. The derivative cohort consisted of 127 asymptomatic patients (age 45±14 years, 84% males) with 41 (32%) end points during a median follow-up of 1375 (interquartile range, 1041-1783) days. In multivariable Cox regression analysis, age, BNP, 3-dimensional vena contracta area, MRI left ventricular end-diastolic volume index, regurgitant volume, and a fraction were identified as independent predictors of end point (all. In asymptomatic severe AR, multimodality and multiparametric model combining 2 imaging indices with natriuretic peptides, showed high accuracy to identify early disease decompensation. Further prospective studies are warranted to explore the clinical benefit of implementing these models to guide patient management.. URL: https://www.. gov; Unique identifier: NCT02910349.

Topics: Adult; Aortic Valve Insufficiency; Echocardiography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

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

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

N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality.. NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2.. The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.

Topics: Aged; Aged, 80 and over; Aortic Valve Insufficiency; Biomarkers; Female; Follow-Up Studies; Humans; Male; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Time Factors; Transcatheter Aortic Valve Replacement; Ventricular Dysfunction, Left

Topics: Aortic Aneurysm; Aortic Dissection; Aortic Valve Insufficiency; Biomarkers; Blood Vessel Prosthesis Implantation; Dyspnea; Heart Failure, Diastolic; Heart Murmurs; Heart Valve Prosthesis Implantation; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls.. The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated.. NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients.. Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.

Topics: Aged; Aortic Valve Insufficiency; Case-Control Studies; Echocardiography; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Wedge Pressure; Scleroderma, Systemic; Stroke Volume; Tricuspid Valve Insufficiency; Troponin I; Ventricular Dysfunction, Left

Transcatheter paravalvular leak closure (TPVLC) offers a viable alternative to reoperation but optimal technical strategy is still to be defined. We present a prospective TPVLC registry in which safety and efficacy of multi-plug, single-stage approach were assessed.. Patients with heart failure (HF) symptoms caused by PVL were qualified for TPVLC by Heart Team. Ante- or retrograde access was employed for mitral while retrograde only for aortic PVLs. Two to 4 AVP 3 devices were simultaneously implanted into each PVL. Endpoints were defined according to VARC-2.. From 64 referred patients 49, with either mechanical valves (n = 30) or stented bioprostheses, were eligible for TPVLC. PVL location was mitral (n = 29) or aortic (n = 20). In aortic group acute procedural success (APS) ratio was 100% and no MACCEs occurred. In mitral group, first-attempt TPVLC was successful in 22 cases (4/4 in transapical and 18/25 in transseptal access). Second-attempt transapical procedure followed transseptal failure in 5 patients. Mitral TPVLC ultimately proved efficient in 89.7% with 76.5% APS. Cumulatively, TPVLC was accomplished in 46 subjects (93.9%) with 78% APS. When successful, it led to a significant decrease of NT-proBNP concentration and HF symptoms regression. Periprocedural safety endpoints were met in three patients and included non-disabling stroke, and two access site-related complications. In device failure group two patients died (end-stage HF) and two others were rehospitalized.. TPVLC with simultaneous deployment of multiple AVP III occluders is feasible with high device success rate and no significant periprocedural complications. The clinical benefits of reduction of HF symptoms and hemolysis are evident after 30 days and persist up to 1 year without recurrence of PVL.

Topics: Aged; Aortic Valve; Aortic Valve Insufficiency; Biomarkers; Bioprosthesis; Cardiac Catheterization; Echocardiography, Doppler, Color; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Equipment Design; Female; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemolysis; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Patient Readmission; Peptide Fragments; Prospective Studies; Prosthesis Failure; Registries; Risk Factors; Stents; Time Factors; Treatment Outcome; Vascular Closure Devices

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

Few prospective data are available regarding long-term outcomes after surgical closure of a ventricular septal defect (VSD).. The objective of this study was to investigate clinical outcomes>30 years after surgical VSD closure.. Patients who underwent surgical VSD closure during childhood between 1968 and 1980 were reexamined every 10 years. In 2012, we invited eligible patients to undergo another examination, which included electrocardiography, Holter monitoring, echocardiography, bicycle ergometry, measurement of N-terminal pro-B-type natriuretic peptide, and subjective health assessment.. Cumulative survival was 86% at 40 years. Causes of mortality were arrhythmia, heart failure, endocarditis, during valvular surgery, pulmonary hypertension, noncardiac causes, and unknown causes. Cumulative event-free survival after surgery was 72% at 40 years. Symptomatic arrhythmias occurred in 13% of patients and surgical or catheter-based reinterventions in 12%. Prevalence of impaired right ventricular systolic function increased from 1% in 2001 to 17% in 2012 (p=0.001). Left ventricular systolic function was impaired but stable in 21% of patients. Aortic regurgitation occurred more often in the last 20 years (p=0.039), and mean exercise capacity decreased (p=0.003). N-terminal pro-B-type natriuretic peptide (median: 11.6 pmol/l [interquartile range: 7.0 to 19.8 pmol/l]) was elevated (>14 pmol/l) in 38% of patients. A concomitant cardiac lesion, for example, patent ductus arteriosus, and aortic cross-clamp time were determinants of late events (hazard ratio: 2.84 [95% confidence interval: 1.23 to 6.53] and hazard ratio: 1.47 per 10 min [95% confidence interval: 1.22 to 1.99], respectively). Patients rated their subjective health status significantly better than a reference population.. Survival up to 40 years after successful surgical VSD closure is slightly lower than in the general Dutch population. Morbidity is not negligible, especially in patients with a concomitant cardiac lesion.

Topics: Adult; Aortic Valve Insufficiency; Arrhythmias, Cardiac; Echocardiography; Exercise Tolerance; Female; Health Status; Heart Septal Defects, Ventricular; Humans; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Patient Outcome Assessment; Peptide Fragments; Prospective Studies; Self Report; Ventricular Dysfunction

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

Topics: Aged; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Prolapse; Echocardiography, Transesophageal; Electrocardiography; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Thoracic Injuries; Treatment Outcome; Wounds, Nonpenetrating

Aortic regurgitation (AR) is an important complication of transcatheter aortic valve implantation (TAVI) and even moderate AR is associated with increased mortality after TAVI. The association with decreased survival is unclear. We aimed to analyse the impact of AR after TAVI as a function of baseline NT-proBNP.. We included 236 consecutive patients implanted in our centre with the SAPIEN and SAPIEN XT valves, via the transfemoral route. AR was evaluated by transthoracic echocardiography. NT-proBNP was measured 24h before implantation and patients were divided according to the median value.. Median age was 85 years (80-89) and 137 (58.1%) were women. Patients with high NT-proBNP had lower left ventricular ejection fraction: 52% (35-65) vs. 63% (55-70), p<0.001, larger telediastolic diameters: 56 mm (49-61) vs. 52 mm (46-56), p=0.01, and more severe aortic stenosis: 0.62 ± 0.15 cm(2) vs. 0.70 ± 0.2 cm(2), p<0.001. Pre-procedural moderate or severe AR (42% vs. 26%, p=0.013) and mitral regurgitation (56% vs. 36%, p=0.004) were more common in the high NT-proBNP group. After TAVI, moderate or severe AR occurred in 26% of patients and was associated with increased 2-year mortality only in the low NT-proBNP group, while patients in the high NT-proBNP group were not affected.. Moderate or severe AR after TAVI was not associated with increased 2-year mortality in patients with high baseline NT-proBNP. Our data suggest that the impact of AR after TAVI is absent in patients with significant pre-procedural AR or mitral regurgitation and more severe aortic stenosis.

Topics: Aged, 80 and over; Aortic Valve Insufficiency; Biomarkers; Cause of Death; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Registries; 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

To evaluate the transcatheter paravalvular leak closure (TPVLC) aptitude to reduce manifestations of heart failure caused by aortic paravalvular leak (PVL).. TPVLC is a valuable alternative to reoperation. While technical feasibility of the method is well established, data on long-term clinical outcome are less abundant.. We launched a prospective registry of patients with clinically significant aortic PVL. They were scheduled for TPVLC with Amplatzer vascular plug (AVP) II and III devices serving as occluders. The efficacy and safety were monitored at 6-month follow-up exam.. The occluder deployment reached a success rate of nearly 90%. Following the procedure, we recorded significant improvement both in terms of patient functional capacity and echocardiographic determinants of left ventricular performance. Simultaneously, NT-proBNP plasma concentration and hemolysis markers decreased. Only local complications related to puncture site occurred.. Heart failure caused by aortic PVL can be safely and efficiently treated with TPVLC using AVP II and III devices as occluders.

Topics: Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Echocardiography; Endovascular Procedures; Female; Fluoroscopy; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Registries; Septal Occluder Device; Treatment Outcome

Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) has been associated with poor outcomes, but little is known about how it evolves over time. We evaluated left ventricular (LV) function, remodeling, and the occurrence and evolution of AR after TAVI by using cardiac MRI.. Forty-three patients treated with transfemoral TAVI underwent cardiac MRI 1 week and 6 months after TAVI. LV volumes and function were assessed by using standard cine MRI sequences. Phase-contrast imaging was performed to quantify the degree of AR. The mean age of the evaluated patients was 80 years, and 65% of patients were women. At baseline MRI, the median LV ejection fraction was 58.1%, which improved significantly at follow-up to 63.4% (P<0.0001). A significant reduction of LV end-diastolic volume (149.7 ± 41.4-140.1 ± 43.9 mL; P=0.014) and of LV mass (156.3 ± 32.8-142.7 ± 39.3 g; P<0.001) was observed. Over time, aortic regurgitant fraction increased slightly but significantly from 5.2% to 7.8% (P=0.04). Subgroup analysis revealed that significant changes of LV ejection fraction, volumes, and mass only occurred in patients with no or mild AR at baseline MRI, whereas those parameters remained unchanged in patients with AR more than or equal to grade II.. By using cardiac MRI in patients with TAVI, a significant improvement of LV function, volume, and mass can be documented. Mild-to-moderate AR is commonly seen, and AR shows a small increase over time. More-than-mild AR seems to prevent LV functional and structural recovery after TAVI.

Topics: Aged; Aged, 80 and over; Aortic Valve Insufficiency; Cardiac Catheterization; Echocardiography; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left; Ventricular Remodeling

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

Aortic regurgitation (AR) is a chronic disease for which there is currently no approved medical treatment. We previously reported in an animal model that β-blockade with metoprolol exerted beneficial effects on left ventricular remodeling and survival. Despite the recent publication of promising human data, β-blockade in chronic AR remains controversial. More data are needed to support this potentially new treatment strategy. We hypothesized that carvedilol might be another safe treatment option in chronic AR, considering its combined β-blocking and α-blocking effects and proven efficacy in patients with established heart failure.. The effects of a 6-month treatment with carvedilol 30 mg/kg/d orally were evaluated in adult Wistar rats with severe AR. Sham-operated and untreated AR animals were used as controls. Carvedilol treatment resulted in less left ventricular hypertrophy and dilatation. Ejection fraction was improved and filling pressures were reduced by carvedilol. β1-Receptor expression was also improved as well as myocardial capillary density. Those beneficial effects were noted despite the presence of drug-induced bradycardia.. Carvedilol exerted protective effects against volume-overload cardiomyopathy in this model of aortic valve regurgitation with preserved ejection fraction. These results suggest a protective class effect of β-blockers. Combined with the recent publication of promising human data, our findings support the need to carefully design a prospective study in humans to evaluate the effects of β-blockers in chronic aortic valve regurgitation.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Bradycardia; Capillaries; Carbazoles; Carvedilol; Chronic Disease; Disease Models, Animal; Extracellular Matrix Proteins; Follistatin-Related Proteins; Gene Expression Regulation; Heart Rate; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Propanolamines; Rats; Rats, Wistar; Receptors, Adrenergic; RNA, Messenger; Stroke Volume; Time Factors; Ultrasonography; Ventricular Function, Left; Ventricular Pressure

This study aimed to examine the relationship between biochemical heart failure markers and conventional left ventricular (LV) measurements and strain assessed by speckle-tracking echocardiography in chronic aortic regurgitation (AR) patients.. LV strain, rotation assessed by speckle-tracking echocardiography, LV measurements, mitral annular plane excursion measured by M-mode, and systolic annular plane velocity measured by tissue Doppler echocardiography were analyzed in 64 controls and 65 chronic AR patients. Reduced LV longitudinal strain with increased apical rotation was seen in normal plasma NT-proBNP patients. Increased NT-proBNP (>400 pg/mL) was associated with reduced longitudinal and circumferential strain, diminished mitral annular plane excursions and systolic annular plane velocity. Global systolic longitudinal strain was an indepentent predictor of NT-proBNP level. Longitudinal strain less than 16.0% was the cutoff value for NT-proBNP>400 pg/mL (P<0.05).. LV strain analysis in conjunction with NT-proBNP evaluation is a useful tool in assessing LV function in AR patients.

Topics: Aortic Valve Insufficiency; Biomarkers; Data Interpretation, Statistical; Diastole; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Reproducibility of Results; Systole; Ventricular Dysfunction, Left

The purpose of this study was to determine the independent and additive prognostic value of B-type natriuretic peptide (BNP) in patients with severe asymptomatic aortic regurgitation and normal left ventricular function.. Early surgery could be advisable in selected patients with chronic severe aortic regurgitation, but there are no uniform criteria to identify candidates who could benefit from this strategy. Assessment of BNP has not been studied for this purpose.. We prospectively evaluated 294 consecutive patients with severe asymptomatic organic aortic regurgitation and left ventricular ejection fraction above 55%. The first 160 consecutive patients served as the derivation cohort and the next 134 patients served as a validation cohort. The combined endpoint was the occurrence of symptoms of congestive heart failure, left ventricular dysfunction, or death at follow-up.. The endpoint was reached in 45 patients (28%) of the derivation set and in 35 patients (26%) of the validation cohort. Receiver-operator characteristic curve analysis yielded an optimal cutoff point of 130 pg/ml for BNP that was able to discriminate between patients at higher risk in both cohorts. BNP was the strongest independent predictor by multivariate analysis in the derivation set (odds ratio: 6.9 [95% confidence interval: 2.52 to 17.57], p < 0.0001) and the validation set (odds ratio: 6.7 [95% confidence interval: 2.9 to 16.9], p = 0.0001).. Among patients with severe asymptomatic aortic regurgitation and normal left ventricular function, BNP ≥130 pg/ml categorizes a subgroup of patients at higher risk. Because of its incremental prognostic value, we believe BNP assessment should be used in the routine clinical evaluation of these patients.

Topics: Aortic Valve Insufficiency; Cohort Studies; Echocardiography; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Prognosis; Prospective Studies; Reproducibility of Results; ROC Curve; 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

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

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

Neurohormones are involved in the physiopathology of heart failure, but little is known about its behavior in significant chronic aortic regurgitation (AR). We aimed at analyzing the behavior of these mediators in AF.. We aimed at analyzing the behavior of these mediators in AF.. We analyzed 89 patients with AF, whose mean age was 33.6+/-11.5 years and of whom 84.6% were males, 60% asymptomatic, all with rheumatic etiology. After the clinical and echocardiographic assessment, plasma measurements of tumor necrosis factor (TNF), soluble TNF receptor types I and II (sTNFRI e sTNFRII), interleukin-6 (IL-6), its soluble receptor (sIL6R), endothelin-1 and B-type natriuretic peptide (BNP) were carried out; 12 healthy individuals were used as controls.. The mean values of the left ventricle diastolic diameter (LVDD) were 71.9+/-8.3mm, whereas the mean values of the LV systolic diameter (LVSD) were 50.4+/-9.3mm. The neurohormonal levels were elevated in patients with AF (TNF 92.65+/-110.24 pg/mL vs. 1.67+/-1.21 pg/ml in controls, p<0.001), (IL-6 7.17+/-7.78 pg/ml vs. 0.81+/-0.38 pg/mL in controls, p=0.0001) and TNFRI (894.75+/-348.87 pg/mL vs. 521.42+/-395.13 pg/ml, p=0.007). Except for the BNP levels, symptomatic and asymptomatic patients presented a similar neurohormonal profile. There was a correlation between TNFRII and LVDD (r=-0.329, p=0.038) and LVSD (r=-0.352, p=0.027). BNP levels were significantly higher in symptomatic patients and only in the latter it was possible to establish a correlation between BNP and ventricular diameters.. Patients with significant chronic AF present high neurohormonal levels, with no correlation with the symptomatic status. The TNFRII and BNP levels could be correlated with ventricular diameters, but only the latter could be correlated with symptoms.

Topics: Adult; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Female; Heart Failure; Humans; Interleukin-6; Male; Natriuretic Peptide, Brain; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Recent application of brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in cardiac valvular disease is very promising.. To test the usefulness of NT-proBNP in the assessment of patients with aortic or mitral regurgitation.. Sixty-seven patients - 23 with aortic and 12 with mitral regurgitation vs. 32 controls - were examined by color Doppler echocardiography, cardiopulmonary exercise testing, Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and plasma NT-proBNP assay at rest (T0) and after maximal physical exercise (T1).. NT-proBNP was significantly higher in patients than in controls, both at T0 (298 +/- 85 vs. 46 +/- 11 pg/ml; P < 0.01) and at T1 (366 +/- 106 vs. 50 +/- 12 pg/ml; P < 0.01). MLWHFQ score was significantly higher in patients (19 +/- 3 vs. 1 +/- 0.6; P < 0.001) with a significant inverse correlation with VO2max (r = -0.538, P < 0.001) and a direct correlation with NT-proBNP (T0: r = 0.415, P < 0.01; T1: r = 0.458, P < 0.01). NT-proBNP was inversely correlated with VO2max (T0: r = -0.444, P < 0.001; T1:r = -0.428, P < 0.001) and directly correlated with left atrial diameter (T0: r = 0.370, P < 0.01; T1: r = 0.409, P = 0.001), and left ventricular mass index (r = 0.279, P < 0.01, and r = 0.272, P < 0.01). No correlations were found between echocardiographic parameters of valvular disease severity and VO2max, NT-proBNP and MLWHFQ.. NT-proBNP is useful in the assessment of the cardiac functional damage secondary to mitral and aortic regurgitation.

Topics: Aortic Valve Insufficiency; Biomarkers; Case-Control Studies; Exercise; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments

To determine whether plasma levels of B-type natriuretic peptide (BNP) predict left ventricular (LV) dysfunction on exercise echocardiography in patients with moderate to severe aortic regurgitation (AR).. Case-control study.. Outpatient cardiology departments.. 39 asymptomatic or mildly symptomatic patients with chronic moderate to severe AR and a normal LV ejection fraction (>50%), and 10 normal controls.. Plasma level of BNP and echocardiographic measures of LV function at rest and immediately after treadmill exercise.. LV end systolic volume index (LVESVI) was significantly increased in AR patients with normal BNP (0.05 for all). However, there were modest but statistically significant associations between the plasma level of BNP and severity of AR indicated by a greater AR:LV outflow tract width ratio (r = 0.37, p = 0.02) and lower diastolic blood pressure (r = -0.44, p = 0.004). Increased BNP was also associated with a greater LVESVI (r = 0.33, p = 0.04) and lower LV longitudinal strain rate (r = -0.037, 0.02) on echocardiography after exercise.. In moderate to severe AR compensatory LV remodelling can occur with no increase in plasma BNP. Increased BNP is associated with more severe regurgitation and changes consistent with early LV dysfunction on exercise echocardiography.

Topics: Adolescent; Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Case-Control Studies; Chronic Disease; Echocardiography, Stress; Exercise Test; Humans; Middle Aged; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR.. This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p<0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001).. NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

Topics: Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Severity of Illness Index; Stroke Volume

To assess plasma B-type natriuretic peptide (BNP) levels in patients with univentricular hearts late after volume unloading by total cavopulmonary connection (TCPC).. Plasma BNP was measured by sandwich immunoassay in 67 patients after a modified Fontan procedure. BNP levels were compared with age and sex-specific normal values, clinical and echocardiographic data, and results of exercise testing.. BNP had a wide range of 5-290 pg/ml, but was normal in 81% of patients, and median BNP was only 13 pg/ml. There was no difference between males and females, between patients with left or right ventricular morphology, and no correlation was found between BNP and age, post-operative follow-up period, maximum exercise capability, peak oxygen uptake, or blood oxygen saturation. New York Heart Association class I patients had lower BNP than class II patients (p=0.04). Plasma BNP concentration was positively correlated to the number of specific sequelae (r=0.59, p<0.001), and to severity of atrioventricular regurgitation (r=0.38, p=0.002). 5/13 patients with elevated BNP died during follow-up.. BNP plasma concentration was normal in the majority of patients up to 15 years after TCPC. Elevated and increasing BNP levels were associated with increased morbidity and late mortality.

Topics: Adolescent; Adult; Aortic Valve Insufficiency; Child; Child, Preschool; Female; Fontan Procedure; Heart Defects, Congenital; Humans; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Pulmonary Artery; Risk Factors; Treatment Outcome; Vena Cava, Inferior

Topics: Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Heart Valve Prosthesis Implantation; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Period; Predictive Value of Tests; Preoperative Care; Severity of Illness Index; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Aortic regurgitation (AR) causes left ventricular (LV) volume overload, leading to progressive LV dilatation and dysfunction. In the present study it was examined whether blockade of angiotensin II type 1 receptor (AT1) could improve survival in cases of chronic severe AR.. AR was induced by puncturing the aortic valves of wild-type (WT) and AT1a knockout (KO) mice. Mice that survived for 4 weeks after the operation were deemed to be a model of chronic severe AR and were followed up for 50 weeks (WT, n=29; KO, n=31). Baseline measurements made 4 weeks after surgery showed similar LV cavity and function in both genotypes. These conditions progressively worsened in both genotypes, but 16 weeks after baseline, KO mice showed significantly less LV dilatation, hypertrophy and interstitial fibrosis than WT mice. Cardiac mRNA expression of B-type natriuretic peptide and type I collagen was lower in KO than WT mice. The 50-week mortality rate was significantly lower among KO (45.2%) than WT (86.2%) mice, and postmortem findings indicated that the lower mortality was attributable to a lower incidence of congestive heart failure.. In cases of chronic severe AR, blockade of AT1 attenuates the progression of LV dilatation, hypertrophy and fibrosis, thereby mitigating heart failure and improving long-term survival.

Topics: Animals; Aortic Valve Insufficiency; Chronic Disease; Disease Models, Animal; Heart Failure; Mice; Mice, Knockout; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 1; RNA, Messenger; Survival Rate; Ventricular Dysfunction, Left; Ventricular Remodeling

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

A noninvasive marker of disease severity and presence of symptoms is required in patients with chronic rheumatic valve disease (RVD).. We sought to test the utility of measuring of N-terminal pro-B type natriuretic peptide (NT-proBNP) in chronic phase RVD. We also evaluated whether echocardiographic measures are interrelated with NT-proBNP levels.. The study comprised 92 patients with RVD (mean age of 40+/-14 years) and 50 age/gender-matched control subjects. Functional status was assessed. Detailed echocardiographic examination was performed and mitral valve score was estimated. Venous blood samples were taken for measuring the level of NT-proBNP.. The plasma levels of NT-proBNP rose with increasing severity of mitral valve stenosis (p<0.001), increasing severity of mitral valve score (p<0.001), increasing severity of clinical symptom (p<0.001), increasing severity of mitral regurgitation (p<0.013), presence of mitral valve calcification (p<0.001), presence of tricuspid valve stenosis (p<0.001), increasing severity of tricuspid regurgitation (p<0.011), presence of aortic stenosis (p=0.043), decreasing left ventricular ejection fraction (p<0.001), presence of left atrial thrombus (p=0.0019), and with increasing left atrium dimensions (p=0.002).. NT-proBNP levels in patients with chronic RVD are a potential marker of disease severity and correlates with symptoms.

Topics: Adolescent; Adult; Aged; Aortic Valve Insufficiency; Biomarkers; Chronic Disease; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Peptide Fragments; Rheumatic Heart Disease; Ultrasonography

Serum B-type natriuretic peptide (BNP) levels reflect myocardial strain and are known to be elevated in patients with heart failure. To determine if BNP levels are elevated in patients with aortic regurgitation, we measured BNP levels in patients with chronic asymptomatic aortic regurgitation and normal left ventricular systolic function.

Topics: Adult; Aged; Aortic Valve Insufficiency; Chronic Disease; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ventricular Function, Left

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Topics: Adult; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Chronic Disease; Echocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Left