Risk stratification for sudden death in heart failure

Clinical trials provide evidence that an empiric approach of implantable cardioverter-defibrillator (ICD) implantation in heart failure patients (ejection fraction =/< 35%) with mild to moderate symptoms reduces mortality rate as compared to the best available medical therapy. However, ejection fraction alone is unable to predict death by progressive pump failure or sudden arrhythmic death, and consequently over half of all patients will not require device therapy over long-term follow-up. Thus, the approach of empiric ICD implantation results in excessive cost in the absence of more specific risk stratification for sudden death. This review summarizes the current noninvasive risk stratifying strategies available in predicting susceptibility to sudden arrhythmic death in heart failure populations.     

Short- and long-term mechanisms of sudden cardiac death in congestive heart failure

This report presents an overview of the problem of treating congestive heart failure. Emphasis is on the arrhythmia component and the complex interrelationships of critical electrolytes and pathophysiologic factors that can lead to sudden cardiac death.     

Obesity,heart failure and sudden death

AIM: To review the direct unfavourable effect of obesity, the most prevalent nutritional and metabolic disease worldwide, on cardiovascular morbidity and mortality. DATA SYNTHESIS: Obesity is associated with high chronic cardiac workload due to the need to supply more blood to peripheral tissue. The high cardiac output is mainly a consequence of the greater requirements of increased lean body mass, and is maintained by an increased stroke volume and high normal heart rate, and sustained by an increase in ventricular mass. The increase in left ventricular (LV) mass also implies an increase in non-muscular tissue that plays a role in the development of electrical abnormalities, heart failure and sudden death. CONCLUSIONS: Obesity per se is a major risk factor for heart failure. Obesity-related LV hypertrophy is in turn associated with varying degrees of systolic and diastolic dysfunction that are not easily recognisable using traditional methods, but are potentially reversible after appropriate, stable moderate weight loss.     

Risk of sudden death in heart failure patients

Sudden death is one of the more important cause of mortality in patients with chronic heart failure. The highest risk occurs among patients with less severe functional impairment, whereas patients in NYHA class IV usually die of progression of heart failure. Predictors of sudden death have been evaluated. Nevertheless, current methods of risk stratification for sudden death are still inadequate, especially in patients with advanced heart failure. Low left ventricular ejection fraction is widely used for the risk stratification, but it lacks of sensitivity and specificity in distinguishing patients with an increased arrhythmic mortality from those with an increased mortality due to pump failure. Unsustained ventricular tachycardia and inducibility at electrophysiological study may help identifying high-risk patients, requiring more aggressive therapy, as the ICD implantation. Heart rate variability and baroreflex sensitivity analysis have been utilized to obtain information on autonomic modulation, but with uncertain conclusion on the identification of high-risk patients. Increased QT dispersion, the presence of T-wave alternans and abnormal signal-averaged electrocardiography have also been proposed, but, up-to-now, any of these parameters showed a strong predictor power. In conclusion, our capability to identifying heart failure patients at risk for arrhythmic death is still far from being satisfactory.     

心力衰竭猝死的防治

心力衰竭是一种终末期心脏疾病。随着人群年龄增高及心肌梗死等其他心脏疾病的成功救治,心力衰竭的患病率显著上升,我国心力衰竭患病率为0.9%。心力衰竭是心脏性猝死(sudden cardiac death,SCD)的常见病因。心脏性猝死发病机制复杂,但大部分由室性心动过速、心室颤动等恶性心律失常引起。因此预防恶性心律失常的发生,及时终止室性心动过速或心室颤动是防治心脏性猝死发生的关键。     

Cell death signalling mechanisms in heart failure

Cardiac disease is a global epidemic that is on the rise, despite the recent advances in cardiovascular research. Once the myocardium is injured, it has a limited capacity to activate reparative mechanisms to restore proper cardiac function, leading to the development of systemic heart failure. Autophagy, under certain conditions, may result in cell death, further emphasizing the controversial issues regarding the autophagic process as an adaptive or maladaptive biological response. Although significant progress in understanding the signalling mechanisms of cell death in myocytes has been made, the role of apoptotic cell death and programmed necrosis during heart failure is not completely understood. Insight to how myocytes determine whether to activate apoptotic or programmed necrosis signalling machinery remains under current investigation because it is a major problem for both scientists and clinicians in treating heart failure patients. Herein, the different modes of cell death implicated in heart failure are highlighted, as well as the role of B-cell lymphoma-2 family members and how mitochondria act as central organelles in directing such cell death mechanisms.     

The changing epidemiology of sudden death in heart failure

Worsening and progressive heart failure has been the most common mode of death in patients with heart failure. With the development of drugs that primarily have modulation of the renin-angiotensin and sympathetic nervous systems as their mechanism, relative importance of progressive heart failure has decreased. Sudden death has become a larger issue and the dominant mode of death in heart failure. This change requires the clinician to redirect therapy to the prevention and treatment of sudden death.     

Genomics,heart failure and sudden cardiac death

Sudden cardiac death (SCD) is among the most common causes of death in developed countries throughout the world. Despite decreased overall cardiac mortality, SCD rates appear to be increasing in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. This unfavorable trend is a consequence of our inability to identify those who will die suddenly from lethal ventricular arrhythmias and to develop effective therapies for all populations at risk. The known risk factors for SCD lack the predictive power needed to generate preventive strategies for the large number of fatal arrhythmic events that occur among lower-risk subsets of the population. Even among recognized high-risk subsets, prediction of SCD remains challenging. With the exception of the implantable cardioverter defibrillator (ICD) there are few effective strategies for the prevention and treatment of SCD. This article discusses the prospect of genomic science as an approach to the identification of patients at high-risk for SCD. While the final common pathway for SCD is malignant ventricular arrhythmias, there are many potential contributors, pathways, and mechanisms by which common genetic variants (polymorphisms) could affect initiation and propagation of life-threatening cardiac arrhythmias. Recent advances in genomic medicine now provide us with novel approaches to both identify candidate genes/pathways and relatively common polymorphisms which may predispose patients to increased risk for SCD. Improved understanding of the relationship between common polymorphisms and SCD will not only improve risk stratification such that ICDs can be targeted to those patients most likely to benefit from them but also provide new insight into the pathophysiology of SCD.     

Timing of sudden death in patients with heart failure

Objectives. The purpose of this study was to determine the timing of sudden death in patients with advanced heart failure.Background. The frequency of sudden cardiac death and myocardial infarction is greatest in the morning hours, suggesting that physiologic processes associated with morning activities may trigger these events. In patients with advanced heart failure, a variety of mechanisms may cause sudden death, and the frequency of their occurrence may differ from that in other patient groups, perhaps altering the timing of sudden death in heart failure.Methods. Deaths among 566 consecutive patients followed up after treatment for advanced heart failure were prospectively categorized as sudden death, death due to heart failure or noncardiac death. For 72 sudden deaths the time of death was determined from witnesses to the event and from death certificates.Results. Sudden death occurred 2.5 times more frequently between 6:01 amand 12 noon than in the three other 6-h intervals, with 46% of deaths occurring during this period (p < 0.005). The morning peak occurred both in patients with coronary artery disease and in those with nonischemic causes of heart failure.Conclusions. Despite a variety of potential mechanisms of sudden death and underlying causes of heart disease in patients with heart failure, the 24-h distribution of sudden death in these patients is similar to that observed in other patient groups. Morning surges in sympathetic nervous system activity may promote a variety of sudden death mechanisms, including ischemic and nonischemic arrhythmias.     

Arrhythmogenic right ventricular dysplasia and sudden cardiac death

ARVD manifests itself by a wide spectrum of clinical presentations from asymptomatic patients to a broad range of ventricular arrhythmia, extrasystoles, tachycardia, or sudden arrhythmic death which can be the first symptom. It is a major cause for sudden death in young people and sportsmen. In known ARVD the risk of sudden death is not easy to assess from the literature, as its natural history is modulated by the wide variety of antiarrhythmic therapies. Hemodynamically ill tolerated ventricular arrhythmia, left ventricular involvement, sports, a youger age below 35, and uncontrolled therapy seem to predict an adverse outcome for these patients. These data may be helpful to decide for an AICD.     

Reducing the risk of sudden death in heart failure with beta-blockers

BackgroundHeart failure (HF) is a serious cardiovascular syndrome that affects nearly 5 million people in the United States. A review of clinical data demonstrates that sudden cardiac death (SCD) accounts for approximately one-third of all HF deaths. This fatal outcome typically involves an unexpected electrical event leading to sustained cardiac arrhythmias resulting in cardiovascular collapse.Methods and ResultsA systematic review of the literature was performed to serve as the basis for this review. Factors contributing directly to incidence of SCD in the HF population may include significant remodeling of the left ventricle (hypertrophy, dilation, and fibrosis) in addition to increased sympathetic activation. Using specific therapies to limit these mechanisms are beneficial in the HF patient by preventing SCD. β-blockers play a key role in the prevention of SCD for patients with HF by limiting the effects of circulating norepinephrine and by reducing left ventricular remodeling.ConclusionsThis review outlines the potential mechanisms and contributing factors of SCD in patients with HF and the impact of β-blocker usage in the prevention of this fatal outcome for this growing patient population.     

Prediction of sudden death in elderly patients with heart failure

Most heart failure (HF) related mortality is due to sudden cardiac death (SCD) and worsening HF, particularly in the case of reduced ejection fraction. Predicting and preventing SCD is an important goal but most works include no or few patients with advanced age, and the prevention of SCD in elderly patients with HF is still controversial. A recent reduction in the annual rate of SCD has been recently described but it is not clear if this is also true in advanced age patients. Age is associated with SCD, although physicians frequently have the perception that elderly patients with HF die mainly of pump failure, underestimating the importance of SCD. Other clinical variables that have been associated to SCD are symptoms, New York Heart Association functional class, ischemic cause, and comorbidities (chronic obstructive pulmonary disease, renal dysfunction and diabetes). Some test results that should also be considered are left ventricular ejection fraction and diameters, natriuretic peptides, non-sustained ventricular tachycardias and autonomic abnormalities. The combination of all these markers is probably the best option to predict SCD. Different risk scores have been described and, although there are no specific ones for elderly populations, most include age as a risk predictor and some were developed in populations with mean age > 65 years. Finally, it is important to stress that these scores should be able to predict any type of SCD as, although most are due to tachyarrhythmias, bradyarrhythmias also play a role, particularly in the case of the elderly.     

Epidemiology of sudden cardiac death in patients with heart failure

Mortality in congestive heart failure (CHF) usually occurs from either progressive worsening of cardiac pump failure or sudden cardiac death (SCD). Medical interventions that counter neurohormonal changes slow the progression of CHF and also prevent SCD. The benefits of medical therapy on SCD prevention have been variable, depending on the type of medical therapy. This article discusses the incidence, prediction, and prevention of SCD in CHF due to ischemic and nonischemic cardiomyopathy.     

Structural pathways and prevention of heart failure and sudden death

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.     

Prevalence and incidence of arrhythmias and sudden death in heart failure

Patients with heart failure are prone to a variety of arrhythmias, symptomatic and asymptomatic, that are prognostically significant and have an important bearing on the management of these patients. However there are some inherent problems in assessing the frequency of these arrhythmias within a large patient population, due to a lack of uniformity in defining heart failure and the transient nature of these rhythms. Patients with heart failure commonly die suddenly. The causes of these deaths are difficult to ascertain accurately and are often presumed arrhythmic. With the advent of effective interventions to prevent sudden death, accurately defining the causal relationship between the arrhythmias and sudden death has assumed great importance to appropriately target therapy. Several attempts have been made to predict such deaths on the basis of non-invasive and invasive diagnostic investigations with variable success. In this article we review the incidence and prevalence of atrial and ventricular arrhythmias and sudden deaths in epidemiological studies, surveys and randomised control trials of patients with heart failure. We discuss the prognostic significance of these arrhythmias, the inherent problems in their diagnosis and whether their presence predicts the risk of sudden deaths and the mode of such deaths in the heart failure population. The role of various investigations in risk stratification of sudden death has also been discussed     

Selecting patients for discussion of the ICD as primary prevention for sudden death in heart failure

This clinical perspective addresses the practical aspects of the decision to implant an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden death in patients with symptomatic heart failure and reduced left ventricular ejection fraction, based on a distillation of recent trial experience. Potentially eligible patients are selected on the basis of left ventricular ejection fraction < 30% to 35% and anticipated survival with good functional capacity beyond 1 year. Communication with these patients focuses on a horizon of 5 years, during which for every 100 patients receiving devices, approximately 30 patients are predicted to die with or without an ICD, while 7 to 8 lives may be saved with the ICD. These estimates are presented in the context of adverse events, including unnecessary shocks, and the possibility that circumstances may arise for which the defibrillator may be inactivated to allow natural death.