natriuretic-peptide--brain and Death--Sudden--Cardiac

Sudden cardiac death (SCD) is an unexpected death caused by a sudden loss of cardiac function, which is currently a global public health problem. Evaluation of the agonal cardiac function of the deceased is a quite important task for the diagnosis of SCD in forensic medicine. Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are currently considered as significant biomarkers for the diagnosis of heart failure in both clinical and forensic practices. To investigate the postmortem evaluation roles of postmortem BNP and NT-proBNP levels for SCD, the present study meta-analyzed eight related studies from Embase, Cochrane Library, PubMed, China Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Data. Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included literature, and the meta-analysis was performed by RevMan 5.3.5 software. Postmortem NT-proBNP in pericardial fluid showed higher levels in the SCD group than that of the non-SCD group with the weighted mean difference = 3665.74, 95% confidence interval: 1812.89-5518.59, and p = 0.0001. However, postmortem levels of BNP in pericardial fluid and NT-proBNP in serum revealed no statistical difference between SCD and non-SCD subjects. The results of present meta-analysis demonstrated that postmortem NT-proBNP in the pericardial fluid could be used as an ancillary indicator for evaluation of agonal cardiac function in forensic medicine.

Topics: Biomarkers; Death, Sudden, Cardiac; Forensic Medicine; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pericardial Fluid

Current biomarkers allow diagnosing a wide array of pathological processes and evaluating effects of therapies and prognosis for cardiological patients. This review focuses on a possibility of using N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity 2 (sST2), galectin-3, and other biomarkers in patients with chronic heart failure for evaluating the risk of life-threatening ventricular tachyarrhythmias and sudden cardiac death.

Topics: Biomarkers; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Tachycardia

Arrhythmic sudden cardiac death (SCD) represents a major worldwide public health problem accounting for 15-20% of deaths. Risk stratification to identify patients at risk of SCD is crucial in order to implement preventive measures in the general population. Several biomarkers have been tested exploring different pathophysiological mechanisms of cardiac conditions. Conflicting results have been described limiting so far their use in clinical practice. The use of new biomarkers such as microRNAs and sex hormones and the emerging role of genetic on risk prediction of SCD is a current research topic showing promising results.This review outlines the role of plasma biomarkers to predict ventricular arrhythmias and SCD in non coronary artery disease with a special focus on their relationship with the genetic biomarkers.

Topics: Arrhythmias, Cardiac; Death, Sudden, Cardiac; Fatty Acids; Genetic Markers; Genetic Predisposition to Disease; Gonadal Steroid Hormones; Humans; Inflammation Mediators; MicroRNAs; Molecular Diagnostic Techniques; Natriuretic Peptide, Brain; NAV1.5 Voltage-Gated Sodium Channel; Phenotype; Predictive Value of Tests; Risk Factors

The natural history of immunoglobulin light chain associated amyloidosis (AL) is determined by the extent of cardiac involvement. Patients with cardiac AL and symptomatic heart failure have a median survival of approximately six months without successful treatment of the underlying plasma cell disorder The outcome in cardiac AL is determined by both the severity of cardiac involvement and the response to treatment. Staging systems using cardiac biomarkers, including NT- proBNP and troponin, have been found to be powerful predictors of prognosis and are used to guide treatment. Arrhythmias are common in cardiac AL and may lead to acute hemodynamic compromise. Sudden cardiac death, often due to pulseless electrical activity, is an important cause of early mortality. Supportive therapy for heart failure is usually limited to diuretics. Beta-blockers, ACE-inhibitors, and angiotensin receptor blockers are poorly tolerated in cardiac AL and should be avoided. Cardiac transplantation is controversial and reserved for highly selected patients with limited extracardiac involvement. The primary target of treatment in cardiac AL is obliteration of the plasma cell clone, using chemotherapy alone or combined with autologous stem cell transplantation. Despite the risk of early mortality, overall survival has improved with advances in disease modifying therapy. Earlier diagnosis and treatment of cardiac AL is crucial to improving survival.

Topics: Aged; Amyloidosis; Atrial Fibrillation; Biomarkers; Cardiomyopathies; Death, Sudden, Cardiac; Early Diagnosis; Female; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Embolism; Troponin

Congestive heart failure is a very real public health issue not only in the United States, but worldwide. Mortality in patients with congestive heart failure is typically either sudden cardiac death or pump failure. Paradoxically, patients with less severe heart failure are at higher relative risk of sudden cardiac death. Defining which patients are best treated with implantable defibrillators and resynchronization is the purpose of this review.

Topics: Biomarkers; Cardiac Resynchronization Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Evidence-Based Medicine; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Myocardial Revascularization; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Predictive Value of Tests; Primary Prevention; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Stroke Volume

Brain natriuretic peptide (BNP) is a major marker for evaluating cardiac function and has been widely used in clinical practice. Recent researches show that BNP is also useful for identification of sudden cardiac death in forensic pathology. This article reviews the molecular structure and biological characteristics of the BNP and its application as a functional indicate in forensic medicine. It shows that the expression of BNP in cardiac muscles, together with the expression of BNP in blood and pericardium liquid can be used to evaluate the pathological physiology changes and dysfunction degrees of the heart during the cardiac sudden death.

Topics: Amino Acid Sequence; Animals; Autopsy; Biomarkers; Death, Sudden, Cardiac; Forensic Pathology; Heart Diseases; Heart Failure; Humans; Immunohistochemistry; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Pericardium; Postmortem Changes; RNA, Messenger

The risk stratification of patients for sudden cardiac death (SCD) remains a challenge. Brain natriuretic peptide (BNP) predicts overall mortality in heart disease but it is unclear how well it predicts SCD. We therefore performed a meta-analysis of studies evaluating the accuracy of BNP to predict SCD and ventricular arrhythmias (VA).. Electronic databases and published bibliographies were systematically searched (1984-2008). We found 14 studies that met our inclusion criteria. Six studies (3543 patients) evaluated BNP to predict SCD in patients without implantable cardioverter defibrillators (ICDs) across a wide range of populations. A raised BNP predicted SCD with a relative risk of 3.68 [95% confidence interval (CI) 1.90, 7.14]. Eight studies (1047 patients) evaluated BNP to predict the occurrence of VA in patients with ICDs. A raised BNP predicted the occurrence of VA with a relative risk of 2.54 (95% CI 1.87, 3.44).. The measurement of BNP has significant value in predicting SCD and VA. However, the benefit of BNP testing in addition to other risk stratification tests is unclear and BNP needs to be evaluated prospectively in combination with other complementary risk stratification tools.

Topics: Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Biomarkers; Cause of Death; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Sex Factors; Ventricular Fibrillation; Ventricular Flutter

Sudden cardiac death(SCD) from early myocardial ischemia is often lack of typically morphological findings and clinical manifestation, thus cases of SCD may be suspected as criminal cases. It is necessary to clarify the cause of death, which is significance for medico-legal investigation. This article reviewed the latest advancement in the studies on the application of inorganic ions, CK-MB, cTn, ANP and BNP for certification of death from SCD in order to provide a practical way for diagnosis of SCD in forensic pathology.

Topics: Atrial Natriuretic Factor; Autopsy; Biomarkers; Calcium; Cause of Death; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Forensic Pathology; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Troponin

Topics: Acute Disease; Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Severity of Illness Index

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Monitoring, Physiologic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism; Pulmonary Wedge Pressure; Renal Dialysis; Stroke; Weight Loss

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure.. Systematic review of studies assessing BNP for prognosis in patients with heart failure or asymptomatic patients.. Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies.. We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data.. 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance-that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk.. Although systematic reviews of prognostic studies have inherent difficulties, including the possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients and for patients with heart failure at all stages of disease.

Topics: Biomarkers; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; Survival Analysis

Topics: Angina, Unstable; Biomarkers; Carrier Proteins; Creatine Kinase; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Humans; Isoenzymes; Myocardial Infarction; Natriuretic Peptide, Brain; Neoplasm Proteins; Syndrome; Troponin I; Troponin T; Tumor Suppressor Proteins

Abstract B-natriuretic peptide (BNP) is a 32-amino acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. BNP levels are elevated in patients with symptomatic left ventricular dysfunction, and levels correlate with severity of symptoms and with prognosis. Numerous studies indicate that BNP may considerably improve the management of patients with heart failure and may become a routine serum parameter in clinical medicine. In this review, the utility of BNP in different clinical settings will be discussed.

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Diagnosis, Differential; Dyspnea; Emergencies; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Reference Values; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Ventricular Dysfunction, Left

In this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level.. In the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation.. In the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause.. All 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (P. Lower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945).

Topics: Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Denmark; Follow-Up Studies; Heart Failure; Heart Failure, Systolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Patients with heart failure (HF) and coronary artery disease (CAD) have a high risk for cardiovascular (CV) events including HF hospitalization, stroke, myocardial infarction (MI) and sudden cardiac death (SCD). The present study evaluated associations of proteomic biomarkers with CV outcome in patients with CAD and HF with reduced ejection fraction (HFrEF), shortly after a worsening HF episode. We performed a case-control study within the COMMANDER HF international, double-blind, randomized placebo-controlled trial investigating the effects of the factor-Xa inhibitor rivaroxaban. Patients with the following first clinical events: HF hospitalization, SCD and the composite of MI or stroke were matched with corresponding controls for age, sex and study drug. Plasma concentrations of 276 proteins with known associations with CV and cardiometabolic mechanisms were analyzed. Results were corrected for multiple testing using false discovery rate (FDR). In 485 cases and 455 controls, 49 proteins were significantly associated with clinical events of which seven had an adjusted FDR < 0.001 (NT-proBNP, BNP, T-cell immunoglobulin and mucin domain containing 4 (TIMD4), fibroblast growth factor 23 (FGF-23), growth differentiation factor-15 (GDF-15), pulmonary surfactant-associated protein D (PSP-D) and Spondin-1 (SPON1)). No significant interactions were identified between the type of clinical event (MI/stroke, SCD or HFH) and specific biomarkers (all interaction FDR > 0.20). When adding the biomarkers significantly associated with the above outcome to a clinical model (including NT-proBNP), the C-index increase was 0.057 (0.033-0.082), p < 0.0001 and the net reclassification index was 54.9 (42.5 to 67.3), p < 0.0001. In patients with HFrEF and CAD following HF hospitalization, we found that NT-proBNP, BNP, TIMD4, FGF-23, GDF-15, PSP-D and SPON1, biomarkers broadly associated with inflammation and remodeling mechanistic pathways, were strong but indiscriminate predictors of a variety of individual CV events.

Topics: Atrial Remodeling; Biomarkers; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Growth Differentiation Factor 15; Heart Failure; Humans; Inflammation; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Proteomics; Stroke; Stroke Volume; Ventricular Dysfunction, Left

The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease.. We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease.. The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30-2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76-3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12-2.44) for NT-proBNP, and 1.65 (95% CI, 1.13-2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0-4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37-1.77) per 1-unit increase in the score.. Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.

Topics: Aged; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Death, Sudden, Cardiac; Female; Heart Injuries; Humans; Inflammation; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin I

The incidence of and factors associated with sudden cardiac death (SCD) early after an acute heart failure (HF) hospital admission have not been well defined.. We assessed SCD and ventricular arrhythmias in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, which included patients with acute HF with reduced or preserved ejection fraction. SCD, resuscitated SCD (RSCD), and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) were adjudicated from randomization through 30 days and were combined into a composite endpoint. Baseline characteristics associated with this composite were determined by logistic regression. RSCD and VT/VF were included as time-dependent variables in a Cox model evaluating the association of these variables with 180-day all-cause mortality. Among 7011 patients, the 30-day all-cause mortality rate was 3.8%; SCD accounted for 17% of these deaths. The 30-day composite event rate was 1.8% (n = 121). Ten patients had more than one event with 30-day Kaplan-Meier event rates of 0.6% for SCD [95% confidence interval (CI) 0.5%-0.9%, n = 43], 0.4% for RSCD (95% CI 0.2%-0.5%, n = 24), and 0.9% for VT/VF (95% CI 0.7%-1.2%, n = 64). In the multivariable model, chronic obstructive pulmonary disease, history of VT, male sex, and longer QRS duration were associated with SCD, RSCD, or VT/VF. A RSCD or VT/VF event was associated with higher 180-day mortality (adjusted hazard ratio 6.6, 95% CI 4.8-9.1, P < 0.0001).. Approximately 2% of patients admitted for acute HF experienced SCD, RSCD, or VT/VF within 30 days of admission, and SCD accounted for 17% of all deaths within 30 days.

Topics: Acute Disease; Aged; Cause of Death; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Patient Admission; Risk Assessment; Risk Factors; Stroke Volume; Survival Rate; Treatment Outcome; United States

Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.. The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.. In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.. Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cause of Death; Death, Sudden, Cardiac; Double-Blind Method; Factor Xa Inhibitors; Female; Growth Differentiation Factor 15; Heart Failure; Hemorrhage; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Troponin T; Warfarin

The risk of sudden cardiac death (SCD) in patients with heart failure after coronary artery bypass graft surgery (CABG) has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing, and clinical predictors of SCD after CABG.. Patients enrolled in the STICH trial (Surgical Treatment of Ischemic Heart Failure) who underwent CABG with or without surgical ventricular reconstruction were included. We excluded patients with prior implantable cardioverter-defibrillator and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths.. Over a median follow-up of 46 months, 113 of 1411 patients who received CABG without (n = 934) or with (n = 477) surgical ventricular reconstruction had SCD; 311 died of other causes. The mean left ventricular ejection fraction at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than did those who died of causes other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31- to 90-day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy, and left ventricular function, end-systolic volume index and B-type natriuretic peptide were most strongly associated with SCD.. The monthly risk of SCD shortly after CABG among patients with a low left ventricular ejection fraction is highest between the first and third months, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative end-systolic volume index or B-type natriuretic peptide.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT0002359.

Topics: Aged; Atrial Fibrillation; Coronary Artery Bypass; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Postoperative Period; Proportional Hazards Models; Receptors, Tumor Necrosis Factor; Risk Factors; Stroke Volume; Ventricular Function, Left

There are limited data about the correlation between brain natriuretic peptide (BNP) levels and arrhythmic risk assessment in patients who receive device therapy for the treatment of heart failure (HF) or for the prevention of sudden cardiac death.. We aimed to investigate the association between BNP levels and the risk of ventricular tachyarrhythmias among mildly symptomatic HF patients who receive an intracardiac defibrillator (ICD) with or without cardiac resynchronization therapy (respectively, CRT-D or CRT).. The study population involved 1197 patients enrolled in MADIT-CRT. Plasma BNP was measured in a core laboratory at baseline and after 1-year follow-up. Ventricular tachycardia/fibrillation (VT/VF) events were identified from ICD/CRT-D interrogations.. Multivariate Cox hazards regression modeling showed that elevated baseline (> median = 72 ng/L) and 1-year BNP were associated with a significant increase in the risk of VT/VF (HR = 1.36, P = .026; and HR = 1.79, P < .001, respectively); and VT/VF or death (HR = 1.37, P = .008; and HR = 1.84, P < .0001, respectively) during follow-up. At 1 year post device implantation, BNP levels were significantly lower among study patients treated with CRT-D as compared with those who received ICD only (P = .014). CRT-D patients who had greater than median reductions in BNP levels (greater than one-third reduction of initial value) experienced a significantly lower risk of subsequent VT/VF (HR = 0.61, P = .021) and VT/VF or death (HR = 0.45, P < .0001) as compared to patients without such reductions.. In MADIT-CRT, elevated baseline and follow-up BNP levels were independent predictors of increased risk for subsequent ventricular tachyarrhythmias, whereas BNP reductions following CRT-D implantation identified patients with a lower incidence of VT/VF during follow-up.

Topics: Aged; Biomarkers; Canada; Cardiac Resynchronization Therapy; Death, Sudden, Cardiac; Europe; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Assessment; Risk Factors; Survival Rate; Tachycardia, Ventricular; Time Factors; United States

Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain.. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by ≈5 months after ACS.. NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event.. http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Biomarkers; Cause of Death; Clopidogrel; Death, Sudden, Cardiac; Electrocardiography; Female; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Tachycardia, Ventricular; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

Topics: Aged; Atorvastatin; Atrial Fibrillation; Cause of Death; Cholesterol; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Factors; Serum Albumin; Survival Rate; Troponin T; Uremia

The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure.. The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown.. HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP.. After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure.. Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.

Topics: Aged; Biomarkers; Cause of Death; Chronic Disease; Death, Sudden, Cardiac; Female; Fibrosis; Galectin 3; Heart Failure, Systolic; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Receptors, Cell Surface; Risk Factors; Stress, Physiological; Ventricular Dysfunction, Left

This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF).. CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints.. Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis.. A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028).. Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).

Topics: Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ubiquinone; Vitamins

Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum.. We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis.. There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19-0.73), p = 0.004, 0.23 (95% CI, 0.08-0.67), p = 0.007, and 0.32 (95% CI, 0.11-0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10-0.54), p = 0.001, 0.18 (95% CI, 0.05-0.60), p = 0.006 and 0.25 (95% CI, 0.07-0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release.. Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS.. ClinicalTrials.gov NCT01377402.

Topics: Acute Coronary Syndrome; Aged; Argentina; Body Mass Index; C-Reactive Protein; Cause of Death; Chest Pain; Death, Sudden, Cardiac; Discriminant Analysis; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Risk Assessment; ROC Curve; Troponin T; Vitamin D

Among patients with non-ST-segment elevation acute coronary syndromes, recurrent ischemia and ventricular arrhythmias detected on continuous electrocardiographic monitoring remain common events that are associated with worse outcomes. The relative clinical significance of both events together is not well described. We determined the risk associated with ischemia (≥1 mm ST depression lasting ≥1 minutes) and ventricular tachycardia (VT) (≥4 beats) detected on 7-day continuous electrocardiographic monitoring in 6,355 patients with non-ST-segment elevation acute coronary syndromes from the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction (MERLIN-TIMI) 36 trial. The patients were categorized into 4 groups according to the presence or absence of VT and ischemia. Cardiovascular death, sudden cardiac death (SCD), myocardial infarction, and recurrent ischemia were assessed during a median follow-up of 348 days. A total of 60.0% patients had no VT or ischemia, 20.0% had VT alone, 14.7% had ischemia alone, and 5.3% had both. The patients with either VT or ischemia were at increased risk of cardiovascular outcomes. The combination of ischemia and VT identified a particularly high-risk population for cardiovascular death (10.1% vs 3.0%, p <0.001), SCD (7.8% vs 0.9%, p <0.001), and myocardial infarction (15.4% vs 6.2%, p <0.001) compared to patients with neither. The addition of arrhythmia and ischemia significantly improved the clinical model for predicting cardiovascular death or SCD (p <0.001). In patients with both ischemia and VT, 66.6% of SCD occurred within 90 days of the non-ST-segment elevation acute coronary syndromes. In conclusion, in >6,300 patients with non-ST-segment elevation acute coronary syndromes, the presence of myocardial ischemia or VT alone, and particularly in combination, was independently associated with poor cardiovascular outcomes and thus provides incremental improvement in early risk stratification.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Diabetes Mellitus; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Recurrence; Risk Assessment; Sex Factors; Stroke Volume; Tachycardia, Ventricular; Troponin

Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin-angiotensin-aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo.. AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function

Topics: Acute Coronary Syndrome; Aged; Amides; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Death, Sudden, Cardiac; Double-Blind Method; Female; Fumarates; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Renin; Renin-Angiotensin System; Tetrazoles; Valine; Valsartan

N-terminal-pro-B-type-natriuretic-peptide (NT-pro-BNP) concentrations are altered in renal failure. This study examined the effect of baseline and change from baseline NT-pro-BNP on cardiovascular outcome and mortality in haemodialysis patients.. On the basis of the German Diabetes and Dialysis Study, which evaluated atorvastatin in 1255 type 2 diabetes mellitus (T2DM) haemodialysis patients (median follow-up 4 years), the impact of NT-pro-BNP on pre-specified, adjudicated endpoints was investigated: sudden death (SD; n = 160), stroke (n = 99), myocardial infarction (MI; n = 200), cardiovascular events (CVEs: cardiac death, MI, stroke; n = 465), all-cause mortality (n = 612). Patients with baseline NT-pro-BNP ≥ 9252 pg/mL (fourth quartile) exhibited a more than four-fold risk of stroke [hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.0-8.4] and a more than two-fold risk of SD (HR 2.0; 95% CI 1.2-3.3), CVE (HR 2.0; 95% CI 1.5-2.7), and mortality (HR 2.1; 95% CI 1.6-2.7) compared with patients with baseline NT-pro-BNP ≤ 1433 pg/mL (first quartile). Change in NT-pro-BNP was strongly associated with SD, CVE, and mortality. Doubling of NT-pro-BNP increased the risk of death by 46% (95% CI 1.1-2.0). Neither baseline nor change in NT-pro-BNP was significantly associated with MI.. Increasing NT-pro-BNP is a risk factor for SD, CVE, and mortality in haemodialysis patients with T2DM. Whether NT-pro-BNP-guided treatment improves outcome needs to be evaluated prospectively.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Factors; Stroke; Treatment Outcome; Young Adult

Despite widespread use of implantable cardioverter defibrillators (ICDs), their cost and the fact that only a certain group of patients fully benefits from the devices require appropriate risk stratification of patients. This study investigated whether altered cardiac autonomic function is associated with the occurrence of ICD discharge or lethal cardiac events.. Fifty-four ICD-treated patients were prospectively followed after assessment of cardiac metaiodobenzylguanidine (MIBG) activity, quantified as the heart-to-mediastinum ratio (HMR), plasma concentration of brain natriuretic peptide (BNP), and left ventricular ejection fraction (LVEF). Patients were divided into 2 groups based on the presence (group A, n = 21) or absence (group B, n = 33) of appropriate ICD discharge during a 15-mo period.. Group A had a significantly lower level of MIBG activity and a higher plasma BNP level than did group B. Univariate analysis revealed BNP level, any medication, and late HMR to be significant predictors, and multivariate analysis showed late HMR to be an independent predictor. An HMR of less than 1.95 with a plasma BNP level of more than 187 pg/mL or an LVEF of less than 50% had significantly increased power to predict ICD shock: positive predictive values, 82% (HMR + BNP) and 58% (HMR + LVEF); negative predictive values, 73% (HMR + BNP) and 77% (HMR + LVEF); sensitivities, 45% (HMR + BNP) and 67% (HMR + LVEF); and specificities, 94% (HMR + BNP) and 70% (HMR + LVEF).. When combined with plasma BNP concentration or cardiac function, cardiac MIBG activity is closely related to lethal cardiac events and can be used to identify patients who would benefit most from an ICD.

Topics: 3-Iodobenzylguanidine; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Selection; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Ventricular Dysfunction, Left

In retrospective studies, statin therapy has been related to decreased incidence of sudden cardiac death (SCD) in heart failure. We sought to prospectively investigate a relation between atorvastatin therapy and SCD in patients with advanced chronic heart failure.. We enrolled 110 patients with heart failure with a left ventricular ejection fraction less than 30% and cholesterol level greater than 150 mg/dL. Fifty-five patients were randomized to atorvastatin (10 mg/day) (statin group); the remaining 55 patients received no statins (controls). Patients were followed for 1 year. At baseline, the two groups did not differ in age, sex, left ventricular ejection fraction, cholesterol, B-type natriuretic peptide, heart rate variability, or QT variability. During follow-up, 29 patients died (26%) and 2 patients (2%) underwent heart transplantation. Of the 29 deaths, 13 were attributed to pump failure, 15 were attributed to SCD, and 1 was attributed to noncardiac causes. All-cause mortality was lower in the statin group (9/55, 16%) than in controls (20/55, 36%) (P = .017). The same was true of the SCD rate (3/55 [5%] vs. 12/55 [22%], P = .012), but not of the pump failure (5/55 [9%] vs. 8/55 [15%], P = .38). SCD-free survival was 2.3-times higher in the statin group than in controls (P = .01).. Atorvastatin therapy seems to be associated with decreased incidence of SCD in patients with advanced chronic heart failure. Larger studies are ongoing to confirm this hypothesis.

Topics: Atorvastatin; Death, Sudden, Cardiac; Disease Progression; Female; Health Status Indicators; Heart Failure; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyrroles; Risk Factors; Stroke Volume

To explore the effect of metoprolol tartrate tablets and recombinant human natriuretic peptide B (NPPB) on sudden cardiac death and malignant arrhythmias in patients with acute myocardial infarction and patients with heart failure (AMI-HF). A total of 105 AMI-HF patients treatedfrom January 2020 and June 2021 were enrolled and divided into Group I (n=53) and Group II (n=52). Both groups received conventional treatment, and Group II was additionally treated with metoprolol tartrate tablets and NPPB. The clinical observation indicators of the two groups of patients were compared. Group II had better left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) (p<0.05). The standard deviation of NN (R-R) interval (SDNN), mean NN (R-R), root mean square of continuous difference (RMSSD) and the percentage of difference between adjacent RR intervals >50ms (pNN50) increased after treatment, with more increase in the Group II (p<0.05). Group II obtained significantly lower levels of B type natriuretic peptide (BNP),N terminal pro B type natriuretic peptide (NT-ProBNP), interleukin (IL)-6 and hs-CRP in contrast to Group I (p<0.05). Markedly higher total response rates were observed in Group II (p<0.05). The combination of metoprolol tartrate tablets and NPPB is effective in treating AMI-HF.

Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Death, Sudden, Cardiac; Drug Therapy, Combination; Female; Heart Failure; Humans; Interleukin-6; Male; Metoprolol; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Recombinant Proteins; Recovery of Function; Retrospective Studies; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Long-term morbidity and mortality of patients with ST-segment-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI) remain substantial. Circulating microRNAs (miRNAs) play an important role in cardiovascular disease development. We aimed to identify circulating miRNAs associated with adverse cardiovascular events after acute myocardial infarction (AMI).. We performed a prospective, nested, case-control study of 932 patients with STEMI who underwent primary PCI. A 3-phase approach was conducted to screen candidate circulating miRNAs in 70 patients who subsequently experienced cardiac death, hospitalization for heart failure, or recurrent AMI (major adverse cardiovascular events [MACE] group) and in 140 patients matched for age, sex, time from symptom onset to blood collection and dual-antiplatelet therapy who did not report adverse cardiovascular events during 2-year follow-up (non-MACE group).. We found that miR-26a-5p, miR-21-5p, and miR-191-5p levels were lower in the MACE group than in the non-MACE group (all P < 0.001). Multivariate conditional logistic regression analysis revealed that miR-26a-5p, miR-21-5p, and miR-191-5p levels were significantly inversely associated with incident primary composite outcomes (all adjusted P < 0.01). Importantly, the combination of these 3 miRNAs plus B-type natriuretic peptide clearly improved the risk scores recommended in the current guidelines, as determined with the use of C-statistics, net reclassification, and integrated discrimination.. Our study provides proof-of-concept in humans that circulating miRNAs are associated with increased rates of distinct cardiovascular events, suggesting that they can serve as effective prognostic biomarkers and therapeutic targets for patients with AMI.

Topics: Biomarkers; Case-Control Studies; China; Circulating MicroRNA; Creatinine; Death, Sudden, Cardiac; Down-Regulation; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Recurrence; Risk Assessment; ST Elevation Myocardial Infarction; Troponin I; Up-Regulation

Sudden death risk stratification of patients with left ventricular systolic dysfunction remains challenging. Retrospective studies have suggested N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be a useful risk stratification tool.. The purpose of this study was to ascertain the utility of NT-proBNP as a predictor of appropriate implantable cardioverter-defibrillator (ICD) therapies in primary prevention ICD recipients.. This was a prospective study of 342 stable patients with left ventricular ejection fraction ≤40% who received a primary prevention ICD. NT-proBNP assay was performed at the time of device implant and used as a dichotomized variable (1st-3rd NT-proBNP quartiles vs 4th NT-proBNP quartile) to predict primary (appropriate ICD therapies) and secondary (death, ICD-deactivation, chronic inotropic support, transplant) outcomes.. Median follow-up was 35.0 months (interquartile range 15.2-55.3). In unadjusted analyses, NT-proBNP predicted both primary (hazard ratio [HR] 1.89; 95% confidence interval [CI] 1.00-3.56); P = .049) and secondary outcomes (HR 2.13; 95% CI 1.18-3.85; P =.012). Multivariable analysis reaffirmed NT-proBNP as a primary outcome predictor (HR 4.31; 95% CI 1.92-9.70; P <.001) but not as a secondary outcome predictor (HR 1.23; 95% CI 0.61-2.50; P = .564). Instead, secondary outcome was predicted by patient age and renal function. In an unadjusted subanalysis limited to patients with blood urea nitrogen <30 mg/dL, NT-proBNP remained a primary endpoint predictor (HR 2.51; 95% CI 1.25-5.05; P = .010) but not a secondary endpoint predictor (HR 1.34; 95% CI 0.52-3.44; P = .541). Receiver operating analyses at 2- and 3-year follow-up timepoints confirmed that NT-proBNP significantly improved the performance of multivariable models designed to predict future appropriate ICD therapies.. In multivariable analysis, NT-proBNP is a reasonable and specific predictor of future appropriate device therapies in primary prevention ICD recipients. In contrast, adjusted NT-proBNP does not predict all-cause mortality.

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Equipment Failure; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Primary Prevention; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

To determine the prognostic role of big endothelin-1 (ET-1) in left ventricular non-compaction cardiomyopathy (LVNC).. We prospectively enrolled patients whose LVNC was diagnosed by cardiac MRI and who had big ET-1 data available. Primary end point was a composite of all-cause mortality, heart transplantation, sustained ventricular tachycardia/fibrillation and implanted cardioverter defibrillator discharge. Secondary end point was cardiac death or heart transplantation.. Altogether, 203 patients (median age 44 years; 70.9% male) were divided into high-level (≥0.42 pmol/L) and low-level (<0.42 pmol/L) big ET-1 groups according to the median value of plasma big ET-1 levels. Ln big ET-1 was positively associated with Ln N-terminal pro-brain natriuretic peptide, left ventricular diameter, but negatively related to age and Ln left ventricular ejection fraction. Median follow-up was 1.9 years (IQR 0.9-3.1 years). Kaplan-Meier analysis showed that, compared with patients with low levels of big ET-1, those with high levels were at greater risk for meeting both primary (p<0.001) and secondary (p<0.001) end points. The C-statistic estimation of Ln big ET-1 for predicting the primary outcome was 0.755 (95% CI 0.685 to 0.824, p<0.001). After adjusting for confounding factors, Ln big ET-1 was identified as an independent predictor of the composite primary outcome (HR 1.83, 95% CI 1.27 to 2.62, p=0.001) and secondary outcome (HR 1.93, 95% CI 1.32 to 2.83, p=0.001).. Plasma big ET-1 may be a valuable index to predict the clinical adverse outcomes in patients with LVNC.

Topics: Adult; Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Endothelin-1; Female; Heart Transplantation; Heart Ventricles; Humans; Isolated Noncompaction of the Ventricular Myocardium; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Stroke Volume; Tachycardia, Ventricular; Ventricular Fibrillation

Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF.. Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis. A series of models were built in a stepwise manner, and were validated in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved and Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trials.. The clinical model for SD included older age, men, lower LVEF, higher heart rate, history of diabetes or myocardial infarction, and HF hospitalization within previous 6 months, all of which were associated with a higher SD risk. The clinical model predicting PFD included older age, men, lower LVEF or diastolic blood pressure, higher heart rate, and history of diabetes or atrial fibrillation, all for a higher PFD risk, and dyslipidaemia for a lower risk of PFD. In each model, the observed and predicted incidences were similar in each risk subgroup, suggesting good calibration. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.71 (95% CI 0.68-0.75) and 0.78 (95% CI 0.75-0.82), respectively. Both models were robust in external validation. Adding ECG and biochemical parameters, model performance improved little in the derivation cohort but decreased in validation. Including NT-proBNP substantially increased discrimination of the SD model, and simplified the PFD model with marginal increase in discrimination.. The clinical models can predict risks for SD and PFD separately with good discrimination and calibration in HFpEF and are robust in external validation. Adding NT-proBNP further improved model performance. These models may help to identify high-risk individuals for device intervention in future trials.. I-Preserve: ClinicalTrials.gov NCT00095238; TOPCAT: ClinicalTrials.gov NCT00094302; CHARM-Preserved: ClinicalTrials.gov NCT00634712.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biomarkers; Biphenyl Compounds; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Heart Failure; Humans; Irbesartan; Male; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Assessment; Sex Factors; Stroke Volume; Tetrazoles

Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.. The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell's C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson's staining was analysed.. During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson's trichrome staining in the myocardium (r=0.198, p<0.05).. NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

Topics: Beijing; Biomarkers; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Survival Rate; Time Factors

Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF).. Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies.. We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial.. NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE.. We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death.. PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658.

Topics: Aged; Aged, 80 and over; Biomarkers; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Stroke Volume

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.

Topics: Aged; Blood Proteins; Cardiomyopathy, Hypertrophic; Cohort Studies; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; Follow-Up Studies; Galectins; Growth Differentiation Factor 15; Heart Failure; Hospitalization; Humans; Interleukin-1 Receptor-Like 1 Protein; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Prognosis; Prospective Studies; Stroke; Tachycardia, Ventricular; Troponin T

Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention.. Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138).. During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%,. In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention.

Topics: Aged; Cardiomyopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Primary Prevention; Proportional Hazards Models; Registries; Republic of Korea; Risk Factors; Treatment Outcome; Ventricular Dysfunction, Left

A Japanese girl with polycystic kidney disease (PKD) developed normally, but at 8 months of age, she was hospitalized for acute onset dyspnea. On the day after admission to hospital, her general condition suddenly became worse. An echocardiogram showed left ventricular dilatation with thin walls, severe mitral valve regurgitation, and a reduced ejection fraction. She died of acute cardiac failure 3 hours after the sudden change. Postmortem analysis with light microscopy showed disarray of cardiomyocytes without obvious infiltration of lymphocytes, and we diagnosed her heart failure as idiopathic dilated cardiomyopathy (DCM). Clinical exome sequencing showed compound heterozygous variants in JPH2 (p.T237A/p.I414L) and a heterozygous nonsense mutation in PKD1 (p.Q4193*). To date, several variants in the JPH2 gene have been reported to be pathogenic for adult-onset hypertrophic cardiomyopathy or DCM in an autosomal dominant manner and infantile-onset DCM in an autosomal recessive manner. Additionally, autosomal dominant polycystic kidney disease is a systemic disease associated with several extrarenal manifestations, such as cardiomyopathy. Here we report a sudden infant death case of DCM and discuss the genetic variants of DCM and PKD.

Topics: Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Fatal Outcome; Female; Heart Failure; Heterozygote; Humans; Infant; Membrane Proteins; Mitral Valve Insufficiency; Muscle Proteins; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Polycystic Kidney, Autosomal Dominant; TRPP Cation Channels

Cardiac disease is the most common cause of sudden death in Western countries. It is known that high-sensitivity troponin I (hs-cTnI), widely used for detection of myocardial injury, is a sensitive biochemical marker. B-type natriuretic peptide (BNP) is a reliable tool for diagnosing heart failure, and for establishing prognosis or disease severity. We aimed to evaluate the diagnostic efficacy of the postmortem determination of BNP in serum alone or in addition to other biomarkers, such as hs-cTnI and MB isoenzyme of creatine kinase (CK-MB), to ascertain whether its determination improves the post-mortem diagnosis of heart failure-associated causes of death. This study involved 133 cadavers with a mean age of 58.2 (± 17.6) years and a mean postmortem interval of 12.8 (±6.6) h. Cases were assigned into two diagnostic groups, according to the cause of death: cardiac deaths (N = 62) and control (N = 71). In the cardiac group, two categories were established according to morphological features of the heart: 'ischemic deaths' (N = 39), and 'congestive heart' (n = 23). Both hs-cTnI and BNP were useful in diagnosing cardiac deaths, whereas CK-MB did not have any diagnostic relevance. hs-cTnI is higher in cases which acute ischemia as the principal pathology, while the presence of high BNP values is significantly related with chronic cardiac situations with significant ventricular overload. Our findings show that postmortem determination of hs-cTnI and BNP provides valuable information; hs-cTnI is useful for diagnosis of cardiac deaths, mainly with ischemic implications, and BNP gave better results for the diagnosis of congestive heart failure.

Topics: Biomarkers; Case-Control Studies; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Discriminant Analysis; Female; Forensic Pathology; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Postmortem Changes; Troponin I

Ventricular arrhythmia (VA) is a major component of sudden cardiac death (SCD). To investigate the expression of brain natriuretic peptide (BNP), endothelin-1 (ET-1), and transforming growth factor-beta 1 (TGF-β1) during VA, we established a rat model of VA induced by BaCl

Topics: Animals; Arrhythmias, Cardiac; Benzamides; Death, Sudden, Cardiac; Dioxoles; Endothelin Receptor Antagonists; Endothelin-1; Gene Expression; Male; Myocardium; Natriuretic Peptide, Brain; Oligopeptides; Rats, Sprague-Dawley; Receptors, Endothelin; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta1

Osteocalcin is a newly identified type of cytokine secreted by osteoblasts, which has an endocrine function, mediates energy and glycol-lipid metabolism, and is closely related to cardiovascular diseases. In this study, we investigated the value of serum osteocalcin levels in predicting left ventricular systolic dysfunction and cardiac death. A total of 258 patients in the Department of Cardiology were included. Two-dimensional echocardiography was performed in all the subjects. The cardiac death of subjects occurring with a median follow-up of 4.6 years was informed via phone calls or the electronic medical records. The serum osteocalcin levels were measured using electrochemiluminescent immunoassay. We found that the median left ventricular ejection fractions (LVEFs) were 62% in men and 63% in women. In the men with a LVEF > 62%, the serum osteocalcin levels were significantly higher than in those with LVEF ≤ 62% (P = 0.042), whereas this difference was absent in the women. Both the serum osteocalcin (β = 0.095, P = 0.028) and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP; β = -0.003, P < 0.01) levels remained independently significantly correlated with LVEF in the men but not in the women. Receiver operating characteristic (ROC) analyses of the men revealed that the serum osteocalcin (P = 0.007), serum NT-pro-BNP (P = 0.018) and serum osteocalcin + NT-pro-BNP (P < 0.01) levels were all significant in identifying left ventricular systolic dysfunction at baseline, but the pairwise comparisons of the three areas under the curves (AUCs) were all non-significant. The men in the lower osteocalcin level group at baseline suffered a greater risk of future cardiac death than those in the higher osteocalcin level group, whereas the result for NT-pro-BNP exhibited the opposite pattern. In conclusion, lower serum osteocalcin levels in the men could identify left ventricular systolic dysfunction and cardiac death in a manner that was not inferior to high serum NT-pro-BNP levels.

Topics: Aged; China; Death, Sudden, Cardiac; Female; Humans; Male; Natriuretic Peptide, Brain; Osteocalcin; Peptide Fragments; Ventricular Dysfunction, Left

Ventricular septal defect (VSD) generally has a good prognosis unless complicated by heart failure (HF). We report a case of sudden infant death because of clinically undiagnosed VSD in a seemingly healthy 16-day-old boy. Although a cardiac murmur was auscultated at birth, detailed clinical examination was not performed. Medicolegal autopsy revealed a perimembranous large VSD with a single coronary artery. The infant was diagnosed to have had HF based on the increased weight of the heart and extremely high serum brain natriuretic peptide levels. Histological examination revealed the degeneration of cardiomyocytes. The large VSD was thought to be the major cause of HF, although single coronary artery-associated cardiomyopathy might have also partially contributed to it. The decline in the physiological neonatal pulmonary resistance, which occurs over the first 1 or 2 weeks following birth, led to the acute progression of HF, resulting in circulatory collapse and sudden death. Detailed clinical examination should be performed for neonates with cardiac murmur to prevent avoidable death.

Topics: Coronary Vessel Anomalies; Death, Sudden, Cardiac; Heart Failure; Heart Septal Defects, Ventricular; Humans; Infant, Newborn; Male; Natriuretic Peptide, Brain

Implantable cardioverter defibrillator (ICD) shocks are associated with a subsequent increased risk of death, and an elevation of cardiac enzymes has been measured after defibrillation testing (DFT). In an experimental swine study, subcutaneous ICD (S-ICD) shocks caused less myocardial damage than traditional ICD shocks. The aim of our study was to investigate the association between S-ICD shock and acute cardiac damage in humans, as evaluated by means of sensitive and highly specific circulating biomarkers.. We calculated the variation in the serum levels of high-sensitivity cardiac troponin I (hs-CTnI) and creatine kinase-MB mass concentration (CK-MB mass), measured before and after an S-ICD shock delivered during intraoperative DFT. We also measured the degree of haemodynamic stress, as the variation in the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and copeptin (CP), after the S-ICD shock. We analysed 30 consecutive patients who received an S-ICD and who underwent DFT by means of a single 65 J shock. The levels of biomarkers did not change from baseline to 1 h post-shock, i.e. hs-CTnI (from 0.029 ± 0.005 ng/mL to 0.030 ± 0.005 ng/mL, P = 0.079) and CK-MB mass (from 1.37 ± 0.17 ng/mL to 1.41 ± 0.18, P = 0.080) and remained stable 6 and 24 h after DFT. The plasma NT-proBNP did not change, whereas CP levels were significantly higher at 1 h post-shock evaluation. However, 6 h after DFT, the levels had returned to the baseline and remained stable at 24 h.. The S-ICD shock did not seem to cause myocardial injuries. Although CP levels temporarily rose after DFT, they returned to basal levels within 6 h, which suggests that DFT does not have long-term prognostic implications. ICD shocks are associated with a subsequent increased risk of death, and an elevation of cardiac enzymes has been measured after DFT. We showed that serum levels of biomarkers of myocardial damage did not increase after high-energy DFT in patients who had undergone S-ICD device implantation. This suggests that S-ICD shock does not have long-term prognostic implications.

Topics: Adult; Biomarkers; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; Glycopeptides; Heart Injuries; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Troponin I

Sudden unexplained cardiac death (SUCD) can occasionally occur in nonelderly patients with epilepsy, psychiatric disorders, or no medical history. This study was conducted to aim to analyze whether values of the biomarkers for heart failure are associated with the SUCD. Serum concentrations of N-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor α were analyzed in 57 nonelderly patients with SUCD who was diagnosed at medicolegal autopsy. The subjects were divided into 3 subgroups according to the medical history: (1) epilepsy, (2) psychiatric disorders, and (3) no specific medical history. The results showed that serum hs-CRP levels were significantly high in patients with epilepsy (P = 0.01) or psychiatric disorders (P = 0.01) as compared with the controls. Also, significantly high concentrations of hs-CRP were observed in psychiatric patients with schizophrenia, compared with the controls (P = 0.003) or the other psychiatric diseases (P = 0.01). The level of N-terminal probrain natriuretic peptide and tumor necrosis factor α did not show a significant difference between the SUCD and the controls. These results might suggest the association between high serum hs-CRP levels and the potential impairment of the cardiac function before the fatal event.

Topics: Adolescent; Adult; Biomarkers; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Death, Sudden, Cardiac; Epilepsy; Female; Heart Failure; Humans; Infant; Male; Mental Disorders; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Tumor Necrosis Factor-alpha; Young Adult

The association between B-type natriuretic peptide (BNP) levels and sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM) remains unclear.. This study evaluated the effect of elevated BNP levels on sudden death risk in a cohort of patients with HCM.. This study included 346 patients with HCM. Plasma BNP levels were measured at the initial evaluation.. The median (interquartile range) BNP level in the study patients was 197.2 (84.4-353.3) pg/mL. During a median (interquartile range) follow-up period of 8.4 (4.2-12.5) years, 37 patients (10.7%) experienced the combined end point of sudden death or potentially lethal arrhythmic events, including 11 patients with sudden death (3.2%), 8 resuscitated after cardiac arrest, and 18 with appropriate implantable defibrillator shocks. Time-dependent receiver operating characteristic curve analysis of the prognostic value of BNP for the combined end point showed that the Harrell's concordance index was 0.748 and the optimal BNP cutoff point was 312 pg/mL. Patients with high BNP levels (>312 pg/mL) were at a significantly higher risk of sudden death (Gray test, P = .001) and the combined end point (Gray test, P < .001) than were patients with low BNP levels (≤312 pg/mL). Multivariable analysis that included BNP levels and established risk factors for sudden death showed that high BNP levels were an independent determinant of the combined end point (adjusted hazard ratio 5.71; 95% confidence interval 2.86-11.4; P < .001).. Elevated BNP levels may be associated with sudden death and the combination of sudden death or potentially lethal arrhythmic events in patients with HCM.

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; ROC Curve; Survival Rate

We prospectively investigated combinations of risk stratifiers including multiple EP diagnostics in a cohort study of ICD patients.. For 672 enrolled patients, we collected history, LVEF, EP study and T-wave alternans testing, 24-h Holter, NT-proBNP, and the eGFR. All-cause mortality and first appropriate ICD shock were predefined endpoints.. The 635 patients included in the final analyses were 63 ± 13 years old, 81% were male, LVEF averaged 40 ± 14%, 20% were inducible at EP study, 63% had a primary prophylactic ICD. During follow-up over 4.3 ± 1.5 years, 108 patients died (4.0% per year), and appropriate shock therapy occurred in n = 96 (3.9% per year). In multivariate regression, age (p < 0.001), LVEF (p < 0.001), NYHA functional class (p = 0.007), eGFR (p = 0.024), a history of atrial fibrillation (p = 0.011), and NT-pro-BNP (p = 0.002) were predictors of mortality. LVEF (p = 0.002), inducibility at EP study (p = 0.007), and secondary prophylaxis (p = 0.002) were identified as independent predictors of appropriate shocks. A high annualized risk of shocks of about 10% per year was prevalent in the upper quintile of the shock score. In contrast, a low annual risk of shocks (1.8% per year) was found in the lower two quintiles of the shock score. The lower two quintiles of the mortality score featured an annual mortality <0.6%.. In a prospective ICD patient cohort, a very good approximation of mortality versus arrhythmic risk was possible using a multivariable diagnostic strategy. EP stimulation is the best test to assess risk of arrhythmias resulting in ICD shocks.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cohort Studies; Death, Sudden, Cardiac; Defibrillators; Defibrillators, Implantable; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

Biomarkers have shown promising results in risk assessment of cardiovascular events. Their role in predicting the risk of sudden cardiac death (SCD) is not well established. We tested the performance of several biomarkers in risk assessment for SCD in patients with coronary artery disease (CAD) and preserved left ventricular function.. The study population consisted of 1,946 CAD patients (68% male; mean age 66.9±8.6 yrs; type 2 diabetes (T2D) 43%) enrolled in the ARTEMIS study. The study subjects underwent examinations with echocardiography and measurement of several biomarkers. The primary endpoint of the study was SCD. During the mean follow up of 76±20 months 50 patients experienced SCD. Elevated high sensitive CRP (hs-CRP, p = 0.001), soluble ST2 (sST2, p<0.001), B-type natriuretic peptide (BNP, p<0.001), and highly sensitive TroponinT (hs-TnT, p<0.001) predicted the occurrence of SCD in univariate analysis. Using the optimal cutoff points, elevated sST2 (≥27.45ng/mL; hazard ratio [HR] 2.7; 95%CI 1.4-5.1, p = 0.003) and hs-TnT (≥15 ng/mL; HR 2.9; 95% CI 1.5-5.6, p = 0.002) were the strongest predictors of SCD followed by hs-CRP (HR 2.4; 95% CI 1.3-4.4, p = 0.004) and BNP (HR 1.9; 95% CI 1.0-3.7, p = 0.046) in adjusted analysis. Combination of elevated hs-TnT and sST2 resulted in adjusted HR of 6.4 (95% CI 2.6-15.5, p<0.001).. Elevated sST2 and hs-TnT predict the occurrence of SCD among patients with CAD and preserved left ventricular function. The association between sST2, hs-TnT and SCD may be explained by an ongoing myocardial apoptosis followed by fibrosis leading to vulnerability to malignant arrhythmias.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Death, Sudden, Cardiac; Female; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Troponin T; Ventricular Function, Left

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients.

Topics: Aged; Aged, 80 and over; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Bortezomib; Cyclophosphamide; Death, Sudden, Cardiac; Dexamethasone; Female; Heart Diseases; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Troponin T; Water-Electrolyte Imbalance

The aim of the present study was to investigate the differential expression of B‑type natriuretic peptide (BNP) between the left and right ventricle (RV) in sudden cardiac death (SCD). A total of 26 forensic autopsy cases of sudden death (survival time <30 min, postmortem interval <48 h or frozen within 6 h following death) in the present institute were examined. The cases consisted of acute ischemic heart disease (AIHD, n=15) with/without apparent myocardial necrosis as a sign of infarction (acute myocardial infarction, n=6; ischemic heart disease, IHD, n=9), and arrhythmogenic right ventricular cardiomyopathy (ARVC/D, n=5), in addition to traffic accidents and high falls without any pre existing heart disease as control (C, total n=6). BNP was investigated in all cases by the colloidal gold method, hematoxylin‑eosin staining, immunohistochemistry (IHC) and the molecular pathological method. The IHC results demonstrated that a positive BNP immunostaining was detected in all groups; however, there was no difference between different causes of death. Pericardial N‑terminal (NT)‑proBNP concentration was significantly increased in deaths resulting from AIHD and ARVC/D compared with control group. The relative quantification of BNP mRNA demonstrated that relative expression levels of BNP mRNA were significantly increased in the left ventricle (LV) in the AIHD group, and in the RV of the ARVC/D group. The relative quantification difference and ratio of BNP mRNA between LV and RV demonstrated a significantly greater value in the AIHD group compared with control group. BNP mRNA in myocardium and NT‑proBNP concentration in pericardial fluid were elevated in SCD patients, and left ventricular dysfunction predominated in AIHD patients, whereas right ventricular dysfunction predominated in ARVC/D patients. The results of the present study suggest the possible use of molecular pathology of BNP for the determination of terminal cardiac function in SCD and analysis of its fatal mechanism in forensic practice.

Topics: Adolescent; Adult; Age Factors; Aged; Autopsy; Death, Sudden, Cardiac; Female; Gene Expression Regulation; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organ Size; Pericardial Fluid; RNA, Messenger; Sex Factors; Young Adult

To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis.. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA.. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （. In myocardial ischemia condition, the higher expression of proBNP in cardiac muscle cell shows that the detection of NT-proBNP in plasma can be useful to differentially diagnose the degree of coronary atherosclerotic heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease.

Topics: Biomarkers; Blotting, Western; Coronary Disease; Death, Sudden, Cardiac; Heart; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Polymerase Chain Reaction

To study the expression pattern of brain natriuretic peptide （BNP） in myocardial tissue from forensic routine cases and to explore its application value in the forensic determination of sudden cardiac death （SCD）.. The data of 96 autopsy cases accepted by the center of Medico-legal Investigation of China Medical University between December 2008 to May 2014 were collected. There were 62 cases in SCD group cardiac and 34 cases in non-SCD group. The myocardial tissues were taken from left and right ventricular wall, respectively. The expressions of BNP protein and BNP mRNA in myocardial tissue were detected by HE staining, immunohistochemical staining, Western blotting and quantitative real-time reverse transcription-polymerase chain reaction （RT-qPCR）, etc.. The immunohistochemical staining of myocardial tissue showed diffusely positive staining in SCD group, and patchily or diffusely positive staining in non-SCD group with lighter degree. The result of Western blotting showed that the expression of BNP protein elevated in left ventricular wall of SCD group. The result of RT-qPCR showed a positive correlation between the BNP mRNA expressions in bilateral ventricular walls and the heart weight, bilateral lung weight, and N-terminal prohormone of brain natriuretic peptide （NT-proBNP） concentration. There were large differences between the BNP mRNA concentrations in SCD group and non-SCD group, and the former was statistically higher （. The expressions of BNP protein and BNP mRNA in myocardial tissue are related to the causes of death. Combined with pathological changes, the expressions of BNP protein and BNP mRNA in myocardial tissue have certainly practical significance for the determination of SCD and the analysis of the death mechanism in the cases related to forensic pathology.

Topics: Autopsy; Biomarkers; Blotting, Western; China; Death, Sudden, Cardiac; Female; Forensic Pathology; Heart Ventricles; Humans; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Real-Time Polymerase Chain Reaction; RNA, Messenger

To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease.. Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting.. Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （. The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease.

Topics: Anaphylaxis; Autopsy; Blotting, Western; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Diagnosis, Differential; Fluorescent Antibody Technique; Forensic Pathology; Humans; Male; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Tryptases

In this study, we investigated the association between brain natriuretic peptide (BNP) levels and tissue Doppler imaging measurements and also screening for deadly mutations in patients with hypertrophic cardiomyopathy (HCM). We enrolled 20 patients diagnosed with HCM (age:10.7±5 years (1-17), 85% male, weight:42.25±23.10 kg, height:141.80±32.45 cm) and 20 age, gender and body weight-matched control subjects. We performed electrocardiography, transthoracic echocardiography, and tissue Doppler echocardiography in each group, as well as genetic tests (for Arg403Gln, Arg453Cys, Arg719Trp and Arg719Gln mutations in MYH7 Exons 13, 14, 19) and BNP in the patients. The patients were divided into two groups according to the presence (Group 1) or absence (Group 2) of left ventricular (LV) outflow tract obstruction. QTc dispersion and the LV ejection fraction and left atrial (LA) volume index were increased in Group 1. The LA volume index and the mitral and septal E/Ea ratio and septum Z-score were increased while the mitral lateral annulus and septal annulus Ea wave velocities and the mitral and tricuspid E/A ratio were decreased in patients with high levels of BNP compared to those with normal BNP levels. There were no mutations that are associated with increased risk of sudden death found in patients included in this study. In the light of our data, we conclude that such parameters BNP levels above the 98 pg/mL, septal thickness Z-score ˃6, and higher mitral and septal E/Ea ratios can be used for management of patients with HCM according to life-threatening conditions.

Topics: Adolescent; Cardiac Myosins; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Death, Sudden, Cardiac; Echocardiography, Doppler; Electrocardiography; Exons; Female; Heart Atria; Humans; Infant; Male; Mitral Valve; Mutation; Myosin Heavy Chains; Natriuretic Peptide, Brain; Risk; Tricuspid Valve; Ventricular Dysfunction, Left; Ventricular Function, Left

Sudden cardiac death (SCD) is the most common etiology of death in hemodialysis patients but not much is known about its risk factors. The goal of our study was to determine the association and risk prediction of SCD by serum N-terminal prohormone of brain natriuretic peptide (NTproBNP) troponin I (cTnI) in hemodialysis patients.. We measured NTproBNP and cTnI in 503 hemodialysis patients of a national prospective cohort study. We determined their association with SCD using Cox regression, adjusting for demographics, co-morbidities, and clinical factors and risk prediction using C-statistic and Net Reclassification Improvement (NRI).. Patients' mean age was 58 years and 54 % were male. During follow-up (median 3.5 years), there were 75 outpatient SCD events. In unadjusted and fully-adjusted models, NTproBNP had a significant association with the risk of SCD. Analyzed as a continuous variable, the risk of SCD increased 27 % with each 2-fold increase in NTproBNP (HR, 1.27 per doubling; 95 % CI, 1.13-1.43; p < 0.001). In categorical models, the risk of SCD was 3-fold higher in the highest tertile of NTproBNP (>7,350 pg/mL) compared with the lowest tertile (<1,710 pg/mL; HR for the highest tertile, 3.03; 95 % CI, 1.56-5.89; p = 0.001). Higher cTnI showed a trend towards increased risk of SCD in fully adjusted models, but was not statistically significant (HR, 1.17 per doubling; 95 % CI, 0.98-1.40; p = 0.08). Sensitivity analyses using competing risk models showed similar results. Improvement in risk prediction by adding cardiac biomarkers to conventional risk factors was greater with NTproBNP (C-statistic for 3-year risk: 0.810; 95 % CI, 0.757 to 0.864; and continuous NRI: 0.270; 95 % CI, 0.046 to 0.495) than with cTnI.. NTproBNP is associated with the risk of SCD in hemodialysis patients. Further research is needed to determine if biomarkers measurement can guide SCD risk prevention strategies in dialysis patients.

Topics: Adult; Biomarkers; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Assessment; Risk Factors; Troponin I

Doberman Pinschers with dilated cardiomyopathy (DCM) are at high risk of sudden cardiac death (SCD). Risk factors for SCD are poorly defined.. To assess cardiac biomarkers, Holter-ECG, echocardiographic variables and canine characteristics in a group of Doberman Pinschers with DCM dying of SCD and in a DCM control group to identify factors predicting SCD.. A longitudinal prospective study was performed in 95 Doberman Pinschers with DCM. Forty-one dogs died within 3 months after the last cardiac examination (SCD-group) and were compared to 54 Doberman Pinschers with DCM surviving 1 year after inclusion. Holter-ECG, echocardiography, measurement of N-terminal prohormone of brain-natriuretic peptide (NT-proBNP), and cardiac Troponin I (cTnI) concentrations were recorded for all dogs.. Volume overload of the left ventricle (left ventricular end-diastolic volume (LVEDV/BSA) > 91.3 mL/m²) was the single best variable to predict SCD. The probability of SCD increases 8.5-fold (CI0.95  = 0.8-35.3) for every 50 mL/m²-unit increment in LVEDV/BSA. Ejection fraction (EF), left ventricular end-systolic volume (LVESV/BSA) and NT-proBNP were highly correlated with LVEDV/BSA (r = -0.63, 0.96, 0.86, respectively). Generated conditional inference trees (CTREEs) revealed that the presence of ventricular tachycardia (VT), increased concentration of cTnI, and the fastest rate (FR) of ventricular premature complexes (VPC) ≥260 beats per minute (bpm) are additional important variables to predict SCD.. Conditional inference trees provided in this study might be useful for risk assessment of SCD in Doberman Pinschers with DCM.

Topics: Animals; Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Dog Diseases; Dogs; Echocardiography; Electrocardiography, Ambulatory; Female; Male; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; Troponin I

Prediction and potential prevention of sudden cardiac death (SCD) due to malignant ventricular arrhythmia (MVA) represent an obvious unmet medical need. We estimated the prognostic relevance of numerous biomarkers associated with future MVA development in patients with coronary artery disease (CAD) over 2 years of follow-up.. Patients with stable documented CAD (n = 97) with a mean age of 61 ± 10 years were prospectively enrolled in a single-center observational cohort study. Heart failure was diagnosed in 68% of the patients (NYHA class II-III). The mean left ventricular ejection fraction (LVEF) was 50 ± 13%, while 20% of patients had LVEF ≤35%. Sixty-two patients underwent myocardial revascularization during the follow-up (mean 25 ± 11 months). Clinical characteristics (age, gender, diabetes, history of coronary disease and arrhythmias, prior interventions and antecedent medications), noninvasive electrophysiological markers [microvolt T-wave alterations, signal-averaged electrocardiography, QT interval duration and alteration, and heart rate turbulence (HRT) and HR variability], laboratory indices [serum creatinine and creatinine clearance, brain natriuretic peptide (BNP), NT-proBNP, and C-reactive protein and troponin T levels] were assessed with regard to the MVA prognosis.. MVA was diagnosed in 11 patients during the prospective follow-up. Prior percutaneous coronary intervention (p < 0.05), MVA or syncope (p < 0.05), on-pump coronary artery bypass grafting during follow-up (p < 0.01), LVEF ≤47% (p < 0.01), a left atrium size ≥4.7 cm (p < 0.05), left atrium index (p = 0.01), filtered QRS duration (p < 0.05), abnormal HRT (x03C7;2 = 6.2, p = 0.01) or turbulence slope (x03C7;2 = 9.5, p < 0.01), BNP ≥158 pg/ml (p < 0.01) and NT-proBNP ≥787 pg/ml (x03C7;2 = 4.4, p < 0.05) were significantly associated with MVA risk by univariate analysis. However, only prior MVA or syncope [odds ratio (OR) 11.1; 95% confidence interval (CI) 2.8-44.4; p < 0.01], abnormal HRT (x041E;R 13.6; 95% CI 2.8-66.1; p < 0.01) and plasma BNP (x041E;R 14.3; 95% CI 3.2-65.0; p < 0.01) remained independent predictors of MVA occurrence by multivariate Cox regression analysis.. Prior syncope or MVA, HRT and elevated plasma BNP were independent MVA predictors, advocating for the prospective screening of high-risk CAD patients for potential SCD awareness.

Topics: Aged; Biomarkers; Cohort Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Tachycardia, Ventricular

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.

Topics: Acute Disease; Adolescent; Biomarkers; Cardiomyopathy, Dilated; Child; Child, Preschool; Chronic Disease; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate

Implantable cardioverter-defibrillator (ICD) implantation is contraindicated in those with <1-year life expectancy.. The aim of this study was to develop a risk prediction score for 1-year mortality in patients with primary prevention ICDs and to determine the incremental improvement in discrimination when serum-based biomarkers are added to traditional clinical variables.. We analyzed data from the Prospective Observational Study of Implantable Cardioverter-Defibrillators, a large prospective observational study of patients undergoing primary prevention ICD implantation who were extensively phenotyped for clinical and serum-based biomarkers. We identified variables predicting 1-year mortality and synthesized them into a comprehensive risk scoring construct using backward selection.. Of 1189 patients deemed by their treating physicians as having a reasonable 1-year life expectancy, 62 (5.2%) patients died within 1 year of ICD implantation. The risk score, composed of 6 clinical factors (age ≥75 years, New York Heart Association class III/IV, atrial fibrillation, estimated glomerular filtration rate <30 mL/min/1.73 m(2), diabetes, and use of diuretics), had good discrimination (area under the curve 0.77) for 1-year mortality. Addition of 3 biomarkers (tumor necrosis factor α receptor II, pro-brain natriuretic peptide, and cardiac troponin T) further improved model discrimination to 0.82. Patients with 0-1, 2-3, 4-6, or 7-9 risk factors had 1-year mortality rates of 0.8%, 2.7%, 16.1%, and 46.2%, respectively.. Individuals with more comorbidities and elevation of specific serum biomarkers were at increased risk of all-cause mortality despite being deemed as having a reasonable 1-year life expectancy. A simple risk score composed of readily available clinical data and serum biomarkers may better identify patients at high risk of early mortality and improve patient selection and counseling for primary prevention ICD therapy.

Topics: Aged; Biomarkers; Creatine Kinase, MB Form; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Primary Prevention; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; Survival Rate; Troponin T; United States

Adult congenital heart disease (ACHD) patients are at risk of late complications including arrhythmias, heart failure and sudden death. High-sensitive troponin-T (hs-TnT) is the standard for diagnosing acute coronary syndrome, but is also associated with cardiac function and prognosis in other cardiac diseases. We aimed to describe hs-TnT level in ACHD patients, and determine its relationship with cardiac function and other biomarkers.. Consecutive ACHD patients, visiting the outpatient clinic, underwent echocardiography, exercise testing and venipuncture on the same day.. In total 587 patients were included (median age 33 [IQR 25-41] years, 58% male, 90% NYHA class I). hs-TnT was above the detection limit of 5 ng/L in 241 patients (41%), of whom 47 (8%) had hs-TnT levels above the 99th percentile of normal of 14 ng/L. hs-TnT levels were highest in patients with a systemic RV or pulmonary hypertension. Patients with normal or non-detectable hs-TnT were younger (32 [IQR 24-40] years) than patient with elevated hs-TnT (42 [IQR 36-60] years, p<0.001). The prevalence of hs-TnT ≥14 ng/L was higher in patients with NYHA ≥II (36%, p<0.001), systemic systolic dysfunction (38%, p<0.001), non-sinus rhythm (43%, p<0.001) and elevated pulmonary pressures (39%, p<0.001). hs-TnT was correlated with NT-proBNP (r=0.400, p<0.001).. hs-TnT above the 99th percentile of normal is observed in a non-trivial portion of stable ACHD patients, especially in those with a systemic RV or elevated pulmonary pressures. Since this biomarker of myocardial damage is related to NT-proBNP and ventricular function, its potential predictive value in ACHD patients seems promising and further investigation of underlying mechanisms is warranted.

Topics: Adult; Arrhythmias, Cardiac; Biomarkers; Death, Sudden, Cardiac; Echocardiography; Electrocardiography; Exercise Test; Female; Heart Defects, Congenital; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Troponin T; Ventricular Function

Marfan syndrome (MFS) is associated with a substantial risk for ventricular arrhythmia and sudden cardiac death (SCD). We used heart rate turbulence (HRT) and deceleration capacity (DC), to evaluate the risk stratification for these patients.. We enrolled 102 patients [45 male (44.1 %), age 40.5 ± 14.6 years] with MFS. Blood samples were obtained to determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Transthoracic echocardiography studies were conducted to evaluate heart function parameters and a 24-h holter ECG was performed. An analysis of two HRT parameters, turbulence onset (TO) and turbulence slope (TS), and DC was performed. Therefore, optimal cut-off values were calculated. Primary endpoint was the combination of SCD, ventricular arrhythmia and arrhythmogenic syncope. Secondary endpoint was total mortality.. During a follow-up of 1145 ± 491 days, 12 (11.7 %) patients reached the primary and 8 (7.8 %) patients the secondary endpoint. Patients reaching the primary were significantly older, had a higher burden of premature ventricular complexes and NT-proBNP levels and lower values of LVEF, DC and HRT TS. Multivariate analysis identified NT-proBNP (HR 1.25, 95 % CI 1.01-1.56, p = .04) and the abnormal HRT (abnormal TS and/or TO (HR 7.04, 95 % CI 1.07-46.27, p = .04) as independent risk predictor of arrhythmogenic events.. Patients with Marfan syndrome are at risk for severe ventricular arrhythmias and SCD. Abnormal HRT parameters and NT-proBNP values are independent risk factors for arrhythmogenic events and SCD. The assessment of these tools may help predicting SCD patients with MFS.

Topics: Adult; Age Factors; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Deceleration; Echocardiography; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Humans; Male; Marfan Syndrome; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Registries; Risk Factors; Ventricular Premature Complexes

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood.

Topics: Age of Onset; Animals; Compliance; Death, Sudden, Cardiac; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Gene Knockout Techniques; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Glomerulus; Long QT Syndrome; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Phenotype; Rats; Rats, Inbred Dahl; Recombinant Fusion Proteins; Renal Insufficiency, Chronic; Signal Transduction

Takotsubo cardiomyopathy (TC) is an acute cardiac syndrome characterized by transient left ventricular dysfunction and relatively good prognosis after discharge. However, cardiac complications during hospitalization remain to be fully determined. We attempted to determine features characterizing patients with adverse clinical outcome by comparing those with cardiac complication and without cardiac complication during hospitalization.. We investigated 107 patients with TC from the Tokyo CCU Network database, comprising 67 cardiovascular centers in the metropolitan area during January 1 to December 31, 2010. Cardiac complications were defined as cardiac death, pump failure (Killip grade≥II), sustained ventricular tachycardia or fibrillation (SVT/VF), and advanced atrioventricular block (AVB). Cardiac complications were observed in 41 patients (37 pump failure complicated by 3 cardiac deaths and 2 SVT/VF and 2 AVB without pump failure), and there was no cardiac complication in the remaining 66 patients. There was no difference in age, peak creatinine kinase level, C-reactive protein level and ST elevation on electrocardiogram. Multiple logistic regression analysis showed that white blood cell count (p=0.039) and brain natriuretic peptide (p=0.001) were independent predictors of in-hospital adverse cardiac complications.. Cardiac complications are relatively high in patients with TC during hospitalization. High white blood cell count and brain natriuretic peptide level are associated with poor clinical outcome in patients with TC.

Topics: Aged; Aged, 80 and over; Atrioventricular Block; Biomarkers; Coronary Care Units; Death, Sudden, Cardiac; Female; Forecasting; Heart Failure; Hospitalization; Humans; Leukocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Registries; Tachycardia, Ventricular; Takotsubo Cardiomyopathy; Time Factors; Tokyo; Ventricular Fibrillation

Sudden cardiac death (SCD) mostly resulting from ventricular arrhythmia remains a cause of mortality in 19-30% of adults with congenital heart defects. Indications for implantable cardioverter-defibrillators in primary prophylaxis are still under research. MicrovoltT wave alternans (MTWA) is one of the SCD risk stratification methods. We determined the incidence of MTWA in these patients and its coincidence with ventricular arrhythmia, as well as risk factors of ventricular arrhythmia/SCD.. 204 patients with complex congenital heart anomalies and 45 healthy volunteers underwent ambulatory ECG monitoring, a cardiopulmonary test, B-type natriuretic peptide assessment, echocardiography and an MTWA test. After excluding technically inadequate traces, the remaining 179 patients and 43 controls were classified into MTWA positive (+), negative (-) and indeterminate (ind) subgroups. Additionally, MTWA (+) and MTWA (ind) formed an 'abnormal' group, labeled MTWA (non-).. Abnormal MTWA was observed more frequently in the study group compared to controls (59 [33.0%] vs. 1 [2.3%], p = 0.000001). The MTWA (non-) group compared to MTWA (-) presented a higher number of males (61.0% vs. 37.5%, p = 0.005), predominance of patients with NYHA > I (44.1% vs. 25.0%, p = 0.007), pulmonary hypertension (16.9% vs. 0.8%, p = 0.00007), lower blood saturation (97% [73-100] vs. 99% [69-100], p = 0.0003), higher incidence of malignant arrhythmia (9 [15.2%] vs. 3 [2.5%], p = 0.003), lower peak oxygen consumption VO2 [mL/kg/min] (23.1 ± 5.9 vs. 26.3 ± 6.7, p = 0.002), higher VE//VCO2 slope (36.0 [25-74] vs. 31.0 [21-58], p = 0.01). Multivariate logistic regression analysis proved that pulmonary hypertension (OR = 13.7, p = 0.03), male gender (OR = 10.4,p = 0.00002), VE/VCO2 slope (OR = 1.07, p = 0.045) and VO2 (OR = 0.89, p = 0.04) increase the probability of MTWA (non-).. Abnormal MTWA is more frequent in adults with congenital heart diseases than in the healthy population. Its probability increases in patients demonstrating clinical findings conducive to lethal arrhythmia like heart failure and pulmonary hypertension.

Topics: Action Potentials; Adolescent; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Biomarkers; Case-Control Studies; Chi-Square Distribution; Comorbidity; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Conduction System; Heart Defects, Congenital; Heart Rate; Humans; Hypertension, Pulmonary; Incidence; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Oxygen Consumption; Poland; Risk Assessment; Risk Factors; Young Adult

Topics: Biomarkers; Death, Sudden, Cardiac; Epilepsy; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Edema; Takotsubo Cardiomyopathy; Young Adult

The cost-effective use of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death requires identification of patients at risk for ventricular tachyarrhythmias, not just for total mortality.. To determine whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) or B-type natriuretic peptide (BNP) are independent predictors of ventricular arrhythmias in patients receiving primary prevention ICDs.. One hundred sixty-one patients with NT-proBNP levels and 403 patients with BNP levels at the time of ICD implantation were retrospectively assessed for the occurrence of first appropriate ICD therapy and mortality.. In multivariable Cox proportional hazards regression analysis, NT-proBNP or BNP levels in the upper 50th percentile were the strongest predictor of ICD therapy after adjustment for sex, age, left ventricular ejection fraction, New York Heart Association class, history of coronary artery disease, blood urea nitrogen, creatinine clearance, and history of atrial fibrillation (hazard ratio [HR] 5.75, P < .001 for NT-proBNP; HR 3.40, P = .01 for BNP). Patients were divided into quartiles on the basis of NT-proBNP or BNP levels. The adjusted HR for ICD therapy in the highest and second highest quartiles of NT-proBNP levels (HR 12.9, P < .001, and HR 4.6, P = .03, respectively) were higher than the adjusted HR for total mortality in these 2 quartiles (HR 3.4, P = .021 and HR 2.3, P = .13, respectively). Similarly, the adjusted HR for ICD therapy in the highest and second highest quartiles of BNP levels (HR 4.74, P = .01 and HR 2.17, P = .04, respectively) were higher than the adjusted HR for total mortality in these 2 quartiles (HR 3.05, P = .01 and HR 1.07, P = .3, respectively).. In this study, elevated baseline NT-proBNP and BNP levels are independently associated with the risk for ventricular tachyarrhythmias, which significantly exceeds the risk for total mortality, in multivariable analysis.

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Retrospective Studies; Risk Factors; Survival Analysis; Tachycardia

Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs.. The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable-adjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α receptor II, pro-brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD.. An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs.. clinicaltrials.gov; Unique Identifier: NCT00733590.

Topics: Aged; Biomarkers; Blood Proteins; Chi-Square Distribution; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; Humans; Inflammation Mediators; Linear Models; Male; Middle Aged; Multivariate Analysis; Myocardium; Natriuretic Peptide, Brain; Patient Selection; Predictive Value of Tests; Primary Prevention; Proportional Hazards Models; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; United States

Among adults with congenital heart diseases (CHD) evaluation of sudden cardiac death (SCD) risk remains a great challenge. Although microvolt T-wave alternans has been incorporated into SCD risk stratification algorithm, its role in adults with CHD still requires investigation. We sought to determine the incidence of MTWA in this specific group and its coincidence with ventricular arrhythmia (VA) and other clinical findings presumably associated with SCD.. A case-control study was performed in which 102 patients with CHD characterized by right ventricle pathology or single ventricle physiology (TGA, UVH, Ebstein's anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated ToF) were compared to 45 age- and sex-matched controls. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessment. After excluding technically inadequate traces, the remaining MTWA results were classified as positive(+), negative(-) and indeterminate(ind). Due to similar prognostic significance MTWA(+) and (ind) were combined into a common group labeled 'abnormal'.. Abnormal MTWA was present more often in the study group, compared to controls (39.2% vs 2.3%, p = 0.00001). Sustained ventricular tachycardia (sVT) was observed more often among subjects with abnormal MTWA compared to MTWA(-): 19.4% vs 3.6%, p = 0.026. The patients with abnormal MTWA had a lower blood saturation (p = 0.047), more often were males (p = 0.031), had higher NYHA class (p = 0.04), worse cardiopulmonary parameters: %PeakVO2 (p = 0.034), %HRmax (p = 0.003). Factors proven to increase probability of abnormal MTWA on multivariate linear regression analysis were: sVT (OR = 20.7, p = 0.037) and male gender (OR = 15.9, p = 0.001); on univariate analysis: male gender (OR = 2.7, p = 0.021), presence of VA (OR = 2.6, p = 0.049), NYHA > I (OR = 2.06, p = 0.033), %HRmax (OR = 0.94, p = 0.005), %PeakVO2 (OR = 0.97, p = 0.042), VE/VCO2slope (OR = 1.05, p = 0.037).. Abnormal MTWA occurs significantly more often in adults with the chosen forms of CHD than among healthy subjects. The probability of abnormal MTWA increases in patients with malignant VA, in males and among subjects with heart failure and cyanosis. MTWA might be of potential role in risk stratification for SCD in adults with CHD.

Topics: Action Potentials; Adolescent; Adult; Aged; Arrhythmias, Cardiac; Biomarkers; Case-Control Studies; Chi-Square Distribution; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Conduction System; Heart Defects, Congenital; Heart Ventricles; Humans; Incidence; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Poland; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Young Adult

Levels of high-sensitivity cardiac troponin T (hs-cTnT) predict secondary cardiovascular events in patients with stable coronary heart disease.. To determine the association of hs-cTnT levels with structural and functional measures of heart disease and the extent to which these measures explain the relationship between hs-cTnT and secondary events.. We measured serum concentrations of hs-cTnT and performed exercise treadmill testing with stress echocardiography in a prospective cohort study of outpatients with coronary heart disease who were enrolled from September 11, 2000, through December 20, 2002, and followed up for a median of 8.2 years.. Twelve outpatient clinics in the San Francisco Bay Area.. Nine hundred eighty-four patients with stable coronary heart disease.. Cardiovascular events (myocardial infarction, heart failure, or cardiovascular death), determined by review of medical records and death certificates.. Of 984 participants, 794 (80.7%) had detectable hs-cTnT levels. At baseline, higher hs-cTnT levels were associated with greater inducible ischemia and worse left ventricular ejection fraction, left atrial function, diastolic function, left ventricular mass, and treadmill exercise capacity. During follow-up, 317 participants (32.2%) experienced a cardiovascular event. After adjustment for clinical risk factors, baseline cardiac structure and function, and other biomarkers (N-terminal portion of the prohormone of brain-type natriuretic peptide and C-reactive protein levels), each doubling in hs-cTnT level remained associated with a 37% higher rate of cardiovascular events (hazard ratio, 1.37 [95% CI, 1.14-1.65]; P = .001).. In outpatients with stable coronary heart disease, higher hs-cTnT levels were associated with multiple abnormalities of cardiac structure and function but remained independently predictive of secondary events. These findings suggest that hs-cTnT levels may detect an element of risk that is not captured by existing measures of cardiac disease severity.

Topics: Adult; Aged; Ambulatory Care Facilities; Biomarkers; C-Reactive Protein; Coronary Disease; Death, Sudden, Cardiac; Echocardiography, Stress; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Outpatients; Predictive Value of Tests; Prospective Studies; Risk Factors; San Francisco; Sensitivity and Specificity; Severity of Illness Index; Surveys and Questionnaires; Troponin T

Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.. We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24-32 (P<.001).. Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.

Topics: Adult; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Exons; Female; Fibrillin-1; Fibrillins; Humans; Kaplan-Meier Estimate; Male; Marfan Syndrome; Microfilament Proteins; Middle Aged; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Tachycardia, Ventricular

Increased levels of B-type natriuretic peptide (BNP) are associated with prolongation of the action potential in ventricular myocardium. We investigated the relation of a BNP increase, QT interval, and sudden cardiac death (SCD) in the presence of heart failure (HF). We enrolled 398 patients with HF, New York Heart Association class III or IV, and left ventricular ejection fraction <40%. At baseline and after 3 months, we measured BNP and the QT interval. A BNP increase was defined as a change in BNP of ≥+10%. The QTc interval was calculated using the Bazett formula. QTc interval prolongation was defined as a change in QTc of ≥+10%. The patients were followed up for 1 year. During a 3-month period, BNP increased significantly in 53% of the patients (group 1) and did not in 47% (group 2). During the same period, the QTc interval was more prolonged in group 1 (+44 ± 12 ms) than in group 2 (+7 ± 6 ms; p = 0.01). During 1 year of follow-up, 20 patients died suddenly (SCD), 16 from pump failure. Although the SCD rates did not differ between the 2 groups (5.7% in group 1 vs 4.2% in group 2, p = 0.53), they were significantly greater in the patients in group 1 with QTc interval prolongation ≥+10% (13.8%, p <0.001). The Kaplan-Meier-derived SCD-free survival rates were 2.9 times greater in patients without QTc interval prolongation than in those with prolonged QTc (p <0.001). QTc interval prolongation was an independent correlate of SCD (p = 0.006), but BNP increase was not (p = 0.32). In conclusion, a BNP increase in patients with HF was associated with an increased risk of SCD only in patients with QTc interval prolongation.

Topics: Aged; Biomarkers; Chi-Square Distribution; Death, Sudden, Cardiac; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Long QT Syndrome; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Prospective Studies; Risk Factors; Survival Rate

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI.. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001).. Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Topics: Age Factors; Aged; Aldosterone; Angioplasty, Balloon, Coronary; Body Mass Index; Brain Ischemia; C-Reactive Protein; Coronary Artery Disease; Creatinine; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Stroke; Stroke Volume; Ventricular Function, Left

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment.. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment.. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Death, Sudden, Cardiac; Deoxyguanosine; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Propanolamines; Prospective Studies; Risk Factors; Treatment Outcome

In investigating death due to mechanical asphyxiation and drowning, a cardiac attack is important for discriminating between possible causes of death and as a contributory factor in death processes; however, general pathologies involving visceral congestion are often similar. The present study compared terminal cardiac dysfunction in these fatalities using the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain. Both mechanical asphyxiation (n=27) and drowning (n=23) showed significantly lower ANP and BNP mRNA expressions in bilateral ventricular walls than sudden cardiac deaths (n=36). In addition, right atrial wall BNP mRNA expression was lower in asphyxiation; however, immunostaining did not demonstrate any difference among these fatalities. Differences among the subtypes of asphyxiation or between fresh- and saltwater drowning were insignificant. These observations suggest a difference between primary heart failure in sudden cardiac death and terminal cardiac dysfunction secondary to fatal asphyxiation or drowning.

Topics: Adult; Aged; Aged, 80 and over; Asphyxia; Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Drowning; Female; Forensic Pathology; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

The association between ongoing myocardial damage and outcomes in patients who have received an implantable cardioverter-defibrillator (ICD) is unclear.. Consecutive patients with cardiomyopathy, who had received an ICD (n = 107, mean age 65 ± 11 years), were prospectively enrolled. Myocardial membrane injury (heart-type fatty acid binding protein [H-FABP] >4.3 ng/mL) and myofibrillar injury (troponin T >0.01 ng/mL) were defined using receiver operating characteristic curves. Patients were followed for a median of 33.6 months, to an end point of appropriate ICD shock or cardiac death. Myocardial membrane injury (45%) and myofibrillar injury (41%) were equally prevalent among patients with cardiomyopathy who had received ICDs. Appropriate ICD shocks or cardiac death occurred in 31% and 15% of patients, respectively. Multivariate Cox regression analysis showed that serum H-FABP levels >4.3 ng/mL, but not troponin T levels, were a significant independent prognostic factor for cardiac events (hazard ratio 5.502, 95% confidence interval 1.705-17.75, P = .004). Subgroup analysis revealed that measuring H-FABP levels was valuable for anticipating event-free survival among patients with ICDs who were receiving amiodarone. High H-FABP levels also predicted subsequent outcomes in patients who had received ICDs for primary or secondary prevention.. Evaluating myocardial damage using H-FABP may be a promising tool for predicting outcomes in patients with cardiomyopathy who have received ICDs.

Topics: Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiomyopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Echocardiography; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Troponin T

Pathologic collagen remodeling has been involved in the occurrence of ventricular arrhythmias and sudden cardiac death in heart failure. The aim of the study was to investigate the relationship between malignant ventricular arrhythmias and cardiac collagen turnover indexes, expressing specific types of derangement in collagen physiology, in stable patients with an implantable cardioverter-defibrillator (ICD).. Seventy-four patients with an ICD and heart failure were studied. They had coronary artery disease (n = 42) or dilated cardiomyopathy, New York Heart Association classes I and II, and left ventricular ejection fraction 29% ± 1%. An ICD had been implanted for secondary (n = 36) or primary prevention of sudden cardiac death. We assessed (1) markers of collagen types I and III synthesis and their ratio: procollagen type I carboxyterminal peptide (PICP), procollagen type III aminoterminal peptide (PIIINP), and PICP/PIIINP; (2) markers of collagen degradation, degradation inhibition, and their ratio: matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase (TIMP) 1 (TIMP-1), and MMP-9/TIMP-1. Patients were prospectively followed up for 1 year. The number of episodes necessitating appropriate interventions for ventricular tachyarrhythmias (>170 beat/min) was related to the assessed parameters.. Multivariate analysis revealed a significant relation between the number of tachyarrhythmic episodes and MMP-9/TIMP-1 (P = .007), PICP/PIIINP (P = .007), and ejection fraction (P = .04). No other significant relation was observed between arrhythmias and the remaining parameters.. In heart failure, biochemical markers indicative of a deranged equilirium in myocardial collagen deposition/degradation and collagen I/III synthesis are related to ventricular arrhythmogenesis. Further studies are needed to investigate their predictive ability.

Topics: Biomarkers; Cardiomyopathy, Dilated; Collagen Type I; Collagen Type III; Coronary Artery Disease; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Follow-Up Studies; Heart Failure; Humans; Interleukin-6; Male; Matrix Metalloproteinase 9; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Stroke Volume; Tachycardia, Ventricular; Tissue Inhibitor of Metalloproteinase-1

Various heart diseases present with sudden death; however, it is difficult to interpret the severity of or difference in respective preexisting and terminal cardiac dysfunction based on conventional morphology. The present study investigated the cardiac pathophysiology employing quantitative mRNA measurement of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain, using autopsy materials consisting of acute ischemic heart disease (AIHD, n=40) with/without the pathology of apparent myocardial necrosis (n=19/21), recurrent myocardial infarction (RMI, n=19), chronic congestive heart disease (CHD, n=11) and right ventricular cardiomyopathy (RVC, n=5), as well as hemopericardium (HP, n=11) due to myocardial infarction (n=5) and aortic rupture (n=6), and acute pulmonary thromboembolism (PTE, n=5). Cardiac death groups showed higher ANP and/or BNP mRNA expressions in the left ventricle than acute fatal bleeding (sharp instrumental injury; n=15) and/or mechanical asphyxiation (strangulation; n=10). AIHD and RMI cases had similar ANP and BNP mRNA expressions in bilateral ventricular walls, but their bilateral atrial levels were lower in RMI. RVC showed higher mRNA expressions of posterior left ventricular BNP, and right ventricular and bilateral atrial ANP and BNP. HP cases had lower BNP mRNA expression in the right ventricular wall, but PTE showed lower ANP and BNP mRNA expressions in the left ventricular wall; however, these mRNA expressions at other sites were similar to those of AIHD. CHD presented findings similar to those of AIHD, but the pericardial BNP level was significantly increased. These observations indicate characteristic molecular biological responses of myocardial natriuretic peptides in individual heart diseases and suggest the possible application of molecular pathology to demonstrate cardiac dysfunction even after death.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Female; Forensic Pathology; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Lung; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organ Size; Pulmonary Embolism; RNA, Messenger

Sudden cardiac death (SCD), the cause of 250,000-450,000 deaths per year, is a major public health problem. The majority of those affected do not have a prior cardiovascular diagnosis. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure and mortality as well as with sudden death in women.. The purpose of this study was to examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population.. The risk of SCD associated with baseline NT-proBNP was examined in 5,447 participants. Covariate-adjusted Cox model regressions were used to estimate the hazard ratios of developing SCD as a function of baseline NT-proBNP.. Over a median follow-up of 12.5 years (maximum 16), there were 289 cases of SCD. Higher NT-proBNP levels were strongly associated with SCD, with an unadjusted hazard ratio of 4.2 (95% confidence interval [2.9, 6.1]; P <.001) in the highest quintile compared with in the lowest. NT-proBNP remained associated with SCD even after adjustment for numerous clinical characteristics and risk factors (age, sex, race, and other associated conditions), with an adjusted hazard ratio for the fifth versus the first quintile of 2.5 (95% confidence interval [1.6, 3.8]; P <.001).. NT-proBNP provides information regarding the risk of SCD in a community-based population of older adults, beyond other traditional risk factors. This biomarker may ultimately prove useful in targeting the population at risk with aggressive medical management of comorbid conditions.

Topics: Age Distribution; Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Confidence Intervals; Death, Sudden, Cardiac; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Sex Distribution; Time Factors; United States

Topics: Biomarkers; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Primary Prevention; Risk Assessment; Sensitivity and Specificity

Syndecan-4 is a transmembrane heparan sulfate-carrying glycoprotein that mediates signal transduction pathways activated by growth factors and cell surface receptors, thereby modulating tissue regeneration, angiogenesis, and focal adhesion. The aim of the present study was to determine the clinical use of serum syndecan-4 concentration for diagnosis of heart failure.. Concentration of serum syndecan-4 and other biomarkers of heart failure was measured in 45 patients with heart failure and 21 healthy subjects. Clinical and echocardiographic parameters of cardiac function were recorded.. Serum syndecan-4 concentration significantly increased in proportion to the decrease in ejection fraction (r=-0.599, p<0.001) and increase in the left ventricular (LV) mass index (r=0.315, p<0.05). Serum syndecan-4 concentration was significantly correlated with LV geometrical parameters (i.e. LV mass index, LV end-diastolic volume, and LV dimension), while B-type natriuretic peptide (BNP) was significantly correlated with pressure-related parameters [i.e. early transmitral flow velocity/early diastolic velocity of the mitral valve annulus (E/e'), right ventricular systolic pressure, and left atrial volume index]. Syndecan-4 concentration did not significantly correlate with plasma BNP, transforming growth factor-1, matrix metalloproteinase-2, and tenascin-C concentrations. Serum syndecan-4 concentration could predict cardiac death and re-hospitalization due to heart failure (area under curve, 0.706, p<0.05).. Serum syndecan-4 concentration shows promise as a novel diagnostic and prognostic biomarker for heart failure. Since syndecan-4 correlated with LV geometrical rather than hemodynamic parameters, serum syndecan-4 may represent a biomarker of LV remodeling in the failing heart.

Topics: Biomarkers; Chronic Disease; Death, Sudden, Cardiac; Echocardiography; Female; Heart Failure; Heart Ventricles; Humans; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Patient Readmission; Prognosis; Stroke Volume; Syndecan-4; Tenascin; Transforming Growth Factors; Ventricular Remodeling

Implantable cardioverter defibrillator (ICD) therapy improves survival in patients at high sudden cardiac death (SCD) risk. However, some patient groups fulfilling indications for ICD therapy may not gain significant benefit: patients whose absolute risk of SCD is low and patients whose risk of death even with an ICD is high. The value of biomarkers in identifying patients' potential for survival benefit from ICD therapy is unknown. We performed a pilot study to investigate this.. Five established cardiovascular biomarkers were measured in patients with ICDs on the background of left ventricular dysfunction: N-terminal pro-brain natriuretic peptide [NT-proBNP], soluble ST2 [sST2], growth differentiation factor-15, C-reactive protein, and interleukin-6. The endpoints were all-cause mortality and survival with appropriate ICD therapy. One hundred and fifty-six patients were enrolled (age 69 years [Q1-Q3 62-77], 85% male, 76% ischaemic aetiology). During a follow-up of 15 ± 3 months, 12 patients died and 43 survived with appropriate ICD therapy. In a Cox proportional hazards model, the strongest predictors of death were Log sST2 (P< 0.001), serum creatinine (P< 0.001), and Log NT-proBNP (P= 0.002). The strongest predictor of survival with appropriate ICD therapy was Log NT-proBNP (P= 0.01).. The biomarkers NT-proBNP and sST2 are promising biomarkers for identifying patients with little potential to gain significant survival benefit from ICD therapy. However, their incremental benefit, in addition to currently available clinical risk prediction models, remains unclear. These results demand a confirmatory prospective cohort study, designed and powered to derive and validate prediction algorithms incorporating these markers.

Topics: Aged; Biomarkers; C-Reactive Protein; Cohort Studies; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Growth Differentiation Factor 15; Humans; Interleukin-1 Receptor-Like 1 Protein; Interleukin-6; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Prospective Studies; Receptors, Cell Surface; Risk Factors; Treatment Outcome

To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF).. A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point.. A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p<0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p<0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were independent predictors of the study end point.. In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiac Output; Chronic Disease; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Failure; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; ROC Curve; Severity of Illness Index; Troponin I

To investigate whether simple and non-invasive measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) and/or C-reactive protein (CRP) can predict perioperative major cardiovascular event (PMCE).. Prospective, single-centre, cohort study.. A 1900-bed tertiary-care university hospital in Seoul, Korea Design and. The predictive power of NT-proBNP, CRP and Revised Cardiac Risk Index (RCRI) for the risk of PMCE (myocardial infarction, pulmonary oedema or cardiovascular death) were evaluated from a prospective cohort of 2054 elective major non-cardiac surgery patients. Optimal cut-off values were derived from receiver operating characteristic curve (ROC) analysis.. PMCE (myocardial infarction, pulmonary oedema or cardiovascular death) within postoperative 30 days.. PMCE developed in a total of 290 patients (14.1%). Each increasing quartile of NT-proBNP or CRP level was associated with a greater risk of PMCE after adjustment for traditional clinical risk factors. The relative risk (RR) of highest versus lowest quartile was 5.2 for NT-proBNP (p<0.001) and 3.7 for CRP (p<0.001). Both NT-proBNP (cut-off = 301 ng/l) and CRP (cut-off = 3.4 mg/l) predicted PMCE better than RCRI (cut-off = 2) by ROC analysis (p<0.001). Moreover, the predictive power of RCRI (adjusted RR = 1.5) could be improved significantly by addition of CRP and NT-proBNP to RCRI (adjusted RR 4.6) (p<0.001).. High preoperative NT-proBNP or CRP is a strong and independent predictor of perioperative major cardiovascular event in non-cardiac surgery. The predictive power of current clinical risk evaluation system would be strengthened by these biomarkers.

Topics: Aged; Biomarkers; C-Reactive Protein; Death, Sudden, Cardiac; Female; Humans; Intraoperative Complications; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Preoperative Care; Prospective Studies; Pulmonary Edema; Risk Assessment

There have been few reports that have analyzed the predictive factors for heart failure death, which is sub-divided into pump failure death and sudden cardiac death, in the long term.. We followed 186 consecutive patients with myocardial infarction (MI) and 115 consecutive patients with non-ischemic heart failure (NIHF) during 73+/-3 months. In the MI group, 26 died from pump failure and 12 died from sudden cardiac death. In the NIHF group, 21 died from pump failure and 9 died from sudden cardiac death. Multivariate analysis revealed that the log B-type natriuretic peptide (BNP) was an independent predictor for pump failure death in both groups. In the MI group, the estimated glomerular filtration rate (eGFR) was an independent predictor for sudden cardiac death. Kaplan-Meier analysis revealed that a high BNP level was a risk factor for pump failure death in either MI or NIHF patients. On the other hand, the sudden cardiac death rate was significantly higher in the MI patients with low eGFR than in those with high eGFR.. The plasma BNP level is an independent predictor for pump failure death in both MI and NIHF patients. The eGFR is an independent predictor for sudden cardiac death in MI patients.

Topics: Aged; Cause of Death; Death, Sudden, Cardiac; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Survival Analysis

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.

Topics: Adult; Bicycling; Biomarkers; Case-Control Studies; Death, Sudden, Cardiac; Female; Heart Diseases; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Physical Exertion

End-stage renal disease patients experience a high incidence of sudden cardiac death. We performed a 5-year prospective study in 230 end-stage renal disease patients, aiming to determine the role of echocardiography and the additional value of serum biomarkers in predicting sudden cardiac death. During follow-up, 24% of all deaths were attributed to sudden cardiac death. In the multivariable Cox regression analysis considering clinical, biochemical, dialysis, and echocardiographic parameters, left ventricular systolic dysfunction emerged as the most significant predictor of sudden cardiac death, followed by a high systolic and a low diastolic blood pressure. An ejection fraction cutoff

Topics: Adult; Aged; Body Mass Index; Creatinine; Death, Sudden, Cardiac; Diabetic Nephropathies; Diastole; Disease-Free Survival; Echocardiography; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis; Probability; Prospective Studies; Regression Analysis; Stroke Volume; Systole; Urea

Ventricular myocytes are known to show increased expression of the cardiac hormones atrial and brain natriuretic peptide (ANP and BNP, respectively) in response to pathological stress on the heart, but their function during the progression of nonischemic dilated cardiomyopathy remains unclear. In this study, we crossed a mouse model of dilated cardiomyopathy and sudden death, which we generated by cardioselectively overexpressing a dominant-negative form of the transcriptional repressor neuron-restrictive silencer factor (dnNRSF Tg mice), with mice lacking guanylyl cyclase-A (GC-A), a common receptor for ANP and BNP, to assess the effects of endogenously expressed natriuretic peptides during progression of the cardiomyopathy seen in dnNRSF Tg mice. We found that dnNRSF Tg;GC-A(-/-) mice were born normally, but then most died within 4 wk. The survival rates among dnNRSF Tg;GC-A(+/-) and dnNRSF Tg mice were comparable, but dnNRSF Tg;GC-A(+/-) mice showed greater systolic dysfunction and a more severe cardiomyopathic phenotype than dnNRSF Tg mice. Collectively, our findings suggest that endogenous ANP/BNP protects the heart against the death and progression of pathological remodeling in a mouse model of dilated cardiomyopathy and sudden death.

Topics: Animals; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Disease Models, Animal; Female; Gene Expression; Kaplan-Meier Estimate; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; Phenotype; Receptors, Atrial Natriuretic Factor; Repressor Proteins; RNA, Messenger; Systole; Ventricular Remodeling

Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been found to predict risk of sudden cardiac death (SCD) in patients with known cardiac disease, and C-reactive protein levels have been found to predict risk among apparently healthy men. However, there are no data on SCD risk prediction for either of these markers in a population of women unselected on the basis of cardiovascular disease.. In a prospective, nested, case-control analysis within the 121,700-participant Nurses' Health Study, 99 cases of definite or probable SCD were identified and matched to 294 controls. In multivariable models that adjusted for coronary heart disease risk factors, glomerular filtration rate, and other biomarkers, the trend across quartiles approached significance for NT-proBNP (rate ratio=2.37 for comparison of the highest and lowest quartile; P for trend=0.05) but not for high-sensitivity C-reactive protein (P for trend=0.60). When examined continuously, both NT-proBNP and high-sensitivity C-reactive protein were significantly associated with SCD risk in age- and fasting-adjusted models (P for linear trend=0.04 and 0.03). Adjustment for coronary heart disease risk factors and other biomarkers strengthened the relationship with NT-proBNP and SCD (relative risk for 1-SD increment=1.49; 95% confidence interval, 1.09 to 2.05; P=0.01) but eliminated the relationship with high-sensitivity C-reactive protein (P=0.34). Women with NT-proBNP levels above the prespecified cut point of 389 pg/mL were at a markedly increased risk of SCD in both models (rate ratio=5.68; 95% confidence interval, 1.78 to 18.2; P=0.003).. In this population of women, baseline levels of NT-proBNP were associated with subsequent risk of SCD. If this association is confirmed in larger prospectively studied populations, these findings might provide another useful marker contributing to efforts to screen and prevent SCD among women.

Topics: Adult; Biomarkers; C-Reactive Protein; Case-Control Studies; Death, Sudden, Cardiac; Female; Humans; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk

Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and disarray. Late gadolinium enhancement in cardiovascular magnetic resonance (CMR) is observed in regions of increased myocardial collagen. The extent of late gadolinium enhancement has been associated with higher prevalence of risk factors of sudden death. The aim of the present study was to describe the clinical characteristics and the presence of risk factors for sudden death in a series of patients from 2 referral centers for HCM in relation to late gadolinium enhancement in CMR.. A total of 120 patients (47 +/- 16 years) were included. All patients fulfilled conventional criteria for HCM. A complete history and clinical examination were performed. Risk factors for sudden death were evaluated. A blinded CMR was performed with late gadolinium enhancement in the left ventricular short-axis orientation. NT pro B-type natriuretic protein (BNP) and C-reactive protein were determined in serum samples. A total of 83 patients (69%) showed late gadolinium enhancement. These patients had higher maximal left ventricular wall thickness (22 +/- 5 versus 17 +/- 3 mm, P < .001), showed more frequently obstruction (42% versus 16%, P = .006), nonsustained ventricular tachycardia (38% versus 8%, P = .001), worse exercise capacity (8 +/- 4 versus 10 +/- 4 METs, P = .003) and increased levels of NT BNP (656 [300-1948] versus 290 [122-948] pg/mL, P = .020). On multivariate analysis, maximal left ventricular wall thickness (P < .001) and nonsustained ventricular tachycardia (P = .011) remained associated with gadolinium-enhanced imaging. Number of risk factors for sudden death was associated with late gadolinium enhancement (OR 2.18, 95%CI 1.45-3.20, P < .001).. Late gadolinium enhancement in CMR is a common finding in HCM. Increased maximal left ventricular wall thickness and nonsustained ventricular tachycardia are associated with late gadolinium enhancement. Associations with risk factors for sudden death and functional status are observed.

Topics: C-Reactive Protein; Cardiomyopathy, Hypertrophic; Contrast Media; Death, Sudden, Cardiac; Exercise Test; Exercise Tolerance; Female; Fibrosis; Gadolinium; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

We sought to study the association between brain natriuretic peptide (BNP) levels and the occurrence of ventricular arrhythmias in patients with left ventricular dysfunction (LVD) and an implantable cardioverter defibrillator (ICD).. This was a prospective study of consecutive, stable, ambulatory patients with moderate and severe ischemic LVD and an ICD. A plasma BNP level was obtained at recruitment. Patients were evaluated every 3-6 mo for a minimum of 1 y. The primary end point was the occurrence of malignant ventricular arrhythmia or sudden cardiac death (SCD).. The cohort consisted of 94 subjects (6 women) with a mean +/- standard deviation (SD) age of 69 +/- 10 y. The ICD implantation indication was primary and secondary prevention of SCD in 49% and 51% of subjects, respectively. A primary end point occurred in 27 patients (29%), and was more frequent in symptomatic heart failure patients and those implanted for secondary prevention of SCD. The median BNP level was significantly higher among patients who experienced an end point (191 pg/ml versus 142 pg/ml, p = 0.03). After controlling for New York Heart Association heart failure class and ICD implantation indication, the odds ratio (OR) for experiencing an adverse outcome among the upper BNP quartile versus all others was 3.5 (95% confidence interval [CI]: 1.2-10.2). Among patients implanted for primary prevention of SCD, none of the patients in the lower BNP quartile (BNP < 91 pg/ml) experienced an adverse outcome.. These results suggest that abnormally high BNP levels not only predict cardiac death, but also arrhythmic death in this patient population, and a low BNP level can serve to identify low risk patients. (c)

Topics: Aged; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Defibrillators, Implantable; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is related to stress-induced myocardial ischemia and/or volume overload, both common in patients with renal dysfunction. This might compromise the prognostic usefulness of NT-pro-BNP in patients with renal impairment before vascular surgery. We assessed the prognostic value of NT-pro-BNP in the entire strata of renal function. In 356 patients (median age 69 years, 77% men), cardiac history, glomerular filtration rate (GFR, ml/min/1.73 m(2)), and NT-pro-BNP level (pg/ml) were assessed preoperatively. Troponin T and electrocardiography were assessed postoperatively on days 1, 3, 7, and 30. The end point was the composite of cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariate analysis was used to evaluate the interaction between GFR, NT-pro-BNP and their association with postoperative outcome. Median GFR was 78 ml/min/1.73 m(2) and the median concentration of NT-pro-BNP was 197 pg/ml. The end point was reached in 64 patients (18%); cardiac death occurred in 7 (2.0%), Q-wave myocardial infarction in 34 (9.6%), and non-Q-wave myocardial infarction in 23 (6.5%). After adjustment for confounders, NT-pro-BNP levels and GFR remained significantly associated with the end point (p = 0.005). The prognostic value of NT-pro-BNP was most pronounced in patients with GFR > or =90 (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.80 to 1.76) compared with patients with GFR 60 to 89 (OR 1.04, 95% CI 1.002 to 1.07), and with GFR 30 to 59 (OR 1.12, 95% CI 1.03 to 1.21). In patients with GFR <30 ml/min/1.73 m(2), NT-pro-BNP levels have no prognostic value (OR 1.00, 95% CI 0.99 to 1.01). In conclusion, the discriminative value of NT-pro-BNP is most pronounced in patients with GFR > or =90 ml/min/1.73 m(2) and has no prognostic value in patients with GFR <30 ml/min/1.73 m(2).

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Renal Insufficiency; Sensitivity and Specificity; Vascular Surgical Procedures

Tachycardia-induced cardiomyopathy is characterized by ventricular systolic dysfunction and congestive heart failure resulting from persistent or highly frequent tachyarrhythmias with uncontrolled heart rate. While reversible and often considered benign, few studies have examined the outcome of the disorder. The clinical characteristics, treatment, and long-term outcomes of 12 consecutive patients with tachycardia-induced cardiomyopathy (9 men, age, 51.9 +/- 17.6 years) were studied. The mean period between the occurrence of tachyarrhythmias and the development of congestive heart failure was 26.0 +/- 34.3 days. The mean heart rate on admission was 156.3 +/- 28.7 beats/min. All patients had severe heart failure with a NYHA functional class of 2.3 +/- 0.5, left ventricular ejection fraction of 0.32 +/- 0.10, and brain natriuretic peptide level of 505.7 +/- 449.1 pg/mL. In all patients, cardiac dysfunction recovered after 53.5 +/- 61.3 days. During the follow-up of 53 +/- 24 months, 2 patients had a recurrence of heart failure with uncontrolled tachyarrhythmia and 1 patient died suddenly. In tachycardia-induced cardiomyopathy, recurrent heart failure with uncontrollable tachyarrhythmia and sudden death were observed after recovery from cardiac dysfunction. A substrate for heart failure and/or life-threatening arrhythmia might persist, and careful, long-term follow-up seems required.

Topics: Adult; Aged; Cardiomyopathies; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Recurrence; Stroke Volume; Tachycardia; Treatment Outcome; Ventricular Dysfunction

To assess the value of plasma NT proBNP levels for predicting adverse outcomes in patients with dilated cardiomyopathy (DCM).. Seventy-eight patients with DCM (EF <40%) with sinus rhythm were enrolled. All patients had undergone echocardiographic examination, coronary angiography, and cardiac catheterisation. Blood samples for plasma NT proBNP levels were taken at rest following echocardiographic examination. Patients were followed up for 660+/-270 days for clinical endpoints defined as; death from worsening heart failure, sudden cardiac death and heart transplantation (Tx).. Clinical end points were observed in 19 patients (5 Tx, 4 sudden cardiac death, 10 death from worsening heart failure). Variables associated with an increased hazard of clinical endpoints in univariate analysis were log NT proBNP, age, NYHA functional class, left ventricle ejection fraction, mitral valve effective regurgitation orifice area, and E wave deceleration time. The plasma level of NT proBNP (Hazard ratio=2.5 [95% CI: 1.3-4.7], p=0.0024) and age (hazard ratio=0.94 [95% CI: 0.90-0.98], p=0.0005) were the independent variables associated with an increased risk of clinical endpoints. NT proBNP plasma level >4500 pg/ml detected patients with clinical endpoints with a sensitivity, and specificity of 72%, 80%, respectively. The event free survival was found to be significantly lower in patients with NT proBNP levels >4500 pg/ml.. NT proBNP seems to be a strong predictor of adverse outcomes in patients with DCM with sinus rhythm and may be used as a reliable biological marker in risk stratification.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Biomarkers; Cardiomyopathy, Dilated; Child; Death, Sudden, Cardiac; Echocardiography; Female; Follow-Up Studies; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Research Design; Sensitivity and Specificity; Stroke Volume; Survival Analysis; Ventricular Dysfunction, Left

The identification of valuable markers of sudden cardiac death (SCD) in patients with established HF remains a challenge. We sought to assess the value of clinical, echocardiographic and biochemical variables to predict SCD in a consecutive cohort of patients with heart failure (HF) due to systolic dysfunction.. A cohort of 494 patients with established HF had baseline echocardiographic and NT-proBNP measurements and were followed for 942+/-323 days.. Fifty patients suffered SCD. Independent predictors of SCD were indexed LA size>26 mm/m2 (HR 2.8; 95% CI 1.5-5.0; p=0.0007), NT-proBNP>908 ng/L (HR 3.1; 95% CI 1.5-6.7; p=0.003), history of myocardial infarction (HR 2.3; 95% CI 1.3-4.1; p=0.007), peripheral oedema (HR 2.1; 95% CI 1.1-3.9; p=0.02), and diabetes mellitus (HR 1.9; 95% CI 1.1-3.3; p=0.03). NYHA functional class, left ventricular ejection fraction and glomerular filtration rate were not independent predictors of SCD in this cohort. Notably, the combination of both LA size>26 mm/m2 and NT-proBNP>908 ng/L increased the risk of SCD (HR 4.3; 95% CI 2.5-7.6; p<0.0001). At 36 months, risk of SCD in patients with indexed LA size26 mm/m2 and NT-proBNP>908 ng/L reached 25% (p<0.0001).. Among HF patients, indexed LA size and NT-proBNP levels are more useful to stratify risk of SCD than other clinical, echocardiographic or biochemical variables. The combination of these two parameters should be considered for predicting SCD in patients with HF.

Topics: Aged; Cardiomegaly; Death, Sudden, Cardiac; Female; Heart Atria; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Sensitivity and Specificity

Brain natriuretic peptide (BNP) or N-terminal pro-BNP (N-BNP) now appears to be the best independent predictor of cardiovascular mortality over and above the conventional ones like blood pressure. This may be because a high BNP/N-BNP is identifying any form of asymptomatic cardiac target organ damage (TOD) [especially silent ischaemia, left ventricular hypertrophy (LVH), left atrial dilatation/atrial fibrillation (LAD/AF) and LV systolic dysfunction (LVSD)]. There are strong hints that BNP/N-BNP will also identify those who are going to develop LVH, LAD/AF, and LVSD in a few years' time. Thus, the prospects are good that BNP/N-BNP could be used to identify 'pancardiac' TOD, even when it is silent and that this information could be 'harnessed' to improve primary prevention. BNP/N-BNP could become to the heart what microalbuminuria is to the kidneys, i.e. an indicator of early, silent TOD.

Topics: Biomarkers; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Primary Prevention; Risk Assessment; Risk Factors; Sensitivity and Specificity

The aim of the study was to examine the predictive value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) versus electrophysiologic study in patients with implantable cardioverter-defibrillators (ICDs) after myocardial infarction (MI). We prospectively studied 99 consecutive patients with a history of MI who underwent ICD implantation for primary or secondary prevention of sudden cardiac death. An electrophysiologic study was performed in all patients. Venous blood samples for NT-pro-BNP measurement were obtained at the beginning of the study. The primary end point was ventricular tachycardia or ventricular fibrillation (VT/VF) and the secondary end point was a composite of death, hospitalization for heart failure, or MI. On multivariate Cox regression analysis, NT-pro-BNP level at or greater than median (497 ng/L) was the only significant predictor for VT/VF occurrence (p = 0.047). Along with amiodarone use (p = 0.001), NT-pro-BNP levels higher than median were also associated with a higher risk of composite clinical events (p = 0.036). Kaplan-Meier analysis showed that patients with NT-pro-BNP level at or greater than median had a higher risk of experiencing VT/VF and composite clinical events than patients with NT-pro-BNP levels less than median (log-rank p <0.05). In conclusion, assay of NT-pro-BNP, which is easy to perform and widely available, is superior to electrophysiologic study for prediction of future outcomes in predominantly secondary prophylactic ICD recipients after MI. In the era of primary prophylactic ICD implantation without preimplantation electrophysiologic study, higher NT-pro-BNP levels might help to improve risk-adjusted concomitant antiarrhythmic therapy and device selection.

Topics: Aged; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Protein Precursors; Risk Factors; Survival Rate

To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM).. 92 consecutive patients with DCM were enrolled and followed up for four years.. Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate.. 23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four-year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H-FABP and plasma BNP were significant variables. According to multivariate analysis, serum H-FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H-FABP and BNP. Patients with an H-FABP concentration at or above the median (> or = 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (> or = 138 pg/ml), H-FABP below the median predicted the worst prognosis among the combinations.. The concentration of serum H-FABP before discharge from hospital may be an independent predictor for critical cardiac events in DCM.

Topics: Biomarkers; Cardiomyopathy, Dilated; Death, Sudden, Cardiac; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Heart Rate; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Survival Rate; Troponin T

Brain natriuretic peptide (BNP) and QRS duration have been reported as independent predictors for cardiac events in patients with heart failure. The present study investigated the relationships between BNP and QRS duration to assess the prognostic value in patients with heart failure.. We prospectively examined 93 patients presenting to our emergency department with heart failure between April 2000 and April 2003 (age 69 +/- 13 years, 53 males, 40 females). BNP level and QRS duration were measured after treatment for heart failure. The efficacy end point was the composite incidence of sudden death, death for progressive heart failure, or readmission for worsening heart failure.. During the mean follow-up period of 720 +/- 470 days, cardiac events occurred in 35 patients (sudden death in 6, death for progressive heart failure in 9, and readmission for worsening heart failure in 20). BNP level was almost equally higher in the three groups with cardiac events (mean +/- SEM; sudden death: 348 +/- 128 pg/ml, death for progressive heart failure: 390 +/- 97 pg/ml, readmission for worsening heart failure: 354 +/- 79 pg/ml) than in patients without cardiac events (213 +/- 34 pg/ml). In contrast, QRS duration was exclusively prolonged in patients with sudden death(mean +/- SEM, 125 +/- 10 msec) compared with the remaining three groups (death for progressive heart failure: 100 +/- 5 msec, readmission for worsening heart failure: 103 +/- 4 msec, no cardiac events: 108 +/- 3 msec). No relationship was found between BNP level and QRS duration in all patients with heart failure (Spearman r = 0.13, p = 0.22).. Increased BNP level was associated with poor prognosis irrespective of mode of cardiac events, and prolonged QRS duration was related to sudden death in our cohort with heart failure. The combination of BNP level and QRS duration may have adjunctive value in predicting the prognosis in patients with heart failure.

Topics: Adult; Aged; Aged, 80 and over; Death, Sudden, Cardiac; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies

Topics: Biomarkers; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Selection; Tachycardia

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

We evaluated a combined assessment of brain natriuretic peptide (BNP) with left ventricular dimensions as a prognostic marker for sudden death in patients with chronic heart failure (CHF). Ventricular dimensions and BNP are separately recognized as prognostic markers for sudden death in patients with CHF.. CHF patients at Stage C and B were registered for a prospective study. From the database, we analyzed 417 patients with coronary arterial disease (CAD) or primary/secondary dilated cardiomyopathy (DCM). Main effects of BNP, left ventricular ejection fraction (EF), LV diastolic dimension (LVDD), and interaction of BNP with the EF and LVDD were tested with Cox's proportional hazard model. BNP in sudden death patients was significantly higher than that in event-free patients. Although multivariate analysis revealed that BNP by itself was not an independent risk factor for sudden death after adjustments, it was revealed that BNP entered the model via interaction with EF as a risk factor associating with sudden death. On the other hand, BNP was an independent risk factor associating with heart failure events (death and hospitalization), and BNP did not enter the model via an interaction with EF.. BNP by itself was an independent risk factor for the heart failure events, but not for sudden death in CHF patients of the present study. However, BNP should be important in predicting sudden death when measured with EF.

Topics: Aged; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis

Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs).. Prospective study.. Tertiary referral center.. Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction < 35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria.. Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit.. During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events.. To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Tachycardia, Ventricular; Ventricular Dysfunction, Left

Topics: Biomarkers; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors

To examine the prognostic contribution of combined cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure (CHF) in the absence of acute coronary syndrome.. Between July 2001 and March 2002, 71 consecutive patients (mean age = 68.4+/-1.4 years, 37 men), hospitalised for heart failure, were studied during hospitalisation and follow up until December 2002. Serum cTnT and NT-proBNP were measured on admission. Actuarial rates of adverse cardiac events, including sudden or CHF death, or rehospitalisation for CHF during follow up were compared with patients grouped according to initial serum cTnT and/or NT-proBNP concentrations. The adverse cardiac event-free rate among the 20 patients with cTnT > or 0.01 ng/ml was significantly lower than the 51 patients with cTnT <0.01 ng/ml (P<0.05). Similarly, the adverse cardiac event-free rate among the 36 patients with NT-proBNP > or =1,357 pg/ml (median) was significantly lower than the 35 patients with NT-proBNP <1,357 pg/ml (P<0.01). The 16 patients with high concentrations of both cTnT and NT-proBNP had a lower adverse cardiac event-free rate than the 31 patients with low cTnT and low NT-proBNP upon commencement of the study (P<0.005).. Measurements of serum cTnT and NT-proBNP were reliable prognostic markers of adverse cardiac event in patients with CHF.

Topics: Aged; Cardiac Output, Low; Chronic Disease; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Patient Readmission; Peptide Fragments; Prognosis; Troponin T

Topics: Atrial Natriuretic Factor; Chronic Disease; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Humans; Natriuretic Peptide, Brain; Prognosis

Given the high incidence of sudden death in patients with chronic heart failure (CHF) and the efficacy of implantable cardioverter-defibrillators, an appropriate tool for the prediction of sudden death is desirable. B-type natriuretic peptide (BNP) has prognostic significance in CHF, and the stimuli for its production cause electrophysiological abnormalities. This study tests BNP levels as a predictor of sudden death.. BNP levels, in addition to other neurohormonal, clinical, and hemodynamic variables, were obtained from 452 patients with a left ventricular ejection fraction (LVEF) < or =35%. For prediction of sudden death, only survivors without heart transplantation (HTx) or a mechanical assist device and patients who died suddenly were analyzed. Up to 3 years, 293 patients survived without HTx or a mechanical assist device, 89 patients died, and 65 patients underwent HTx. Mode of death was sudden in 44 patients (49%), whereas 31 patients (35%) had pump failure and 14 patients (16%) died from other causes. Univariate risk factors of sudden death were log BNP (P=0.0006), log N-terminal atrial natriuretic peptide (P=0.003), LVEF (P=0.005), log N-terminal BNP (P=0.006), systolic blood pressure (P=0.01), big endothelin (P=0.03), and NYHA class (P=0.04). In the multivariate model, log BNP level was the only independent predictor of sudden death (P=0.0006). Using a cutoff point of log BNP <2.11 (130 pg/mL), Kaplan-Meier sudden death-free survival rates were significantly higher in patients below (99%) compared with patients above (81%) this cutoff point (P=0.0001).. BNP levels are a strong, independent predictor of sudden death in patients with CHF.

Topics: Adrenergic beta-Antagonists; Alprostadil; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiotonic Agents; Chronic Disease; Comorbidity; Death, Sudden, Cardiac; Endothelin-1; Endothelins; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Factors; Stroke Volume; Survival Analysis; Treatment Outcome