Current role of device therapy to reduce sudden cardiac death in heart failure

Sudden cardiac death (SCD) continues to be a major contributor to mortality in patients with heart failure (HF) despite recent advances in medical therapy. Device therapy, including the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT), serves as an adjunct in reducing HF mortality. Several clinical trials support the prophylactic use of the ICD in reducing mortality in certain HF populations and have established the clinical benefits of CRT in advanced HF. More recently, the Comparison of Medical Therapy Pacing and Defibrillation in Heart Failure trial was the first study to demonstrate a survival benefit of CRT alone or in conjunction with an ICD. This article reviews the most pertinent data regarding the role of device therapy in reducing SCD in HF and addresses future challenges faced by device manufacturers and clinicians.     

Update on implantable cardioverter defibrillator trials

Many randomized trials of implantable cardioverter defibrillator (ICD) therapy versus medical treatment for the prevention of death in survivors of cardiac arrest or in patients at high risk of sudden cardiac death (SCD) have been reported. ICD therapy has been consistently efficacious in preventing SCD. ICD therapy has generally favorably impacted total mortality, but this has depended upon the control group's risk for arrhythmic and nonarrhythmic mortality. In these trials, predictors of sudden or total mortality better than ventricular dysfunction have not emerged. This review summarizes the randomized ICDs trials and the impact ICDs have on SCD prevention.     

植入心律转复除颤器作为心力衰竭患者心脏性猝死的一级预防

心力衰竭是多种心脏疾病发展至晚期的一个严重临床综合征,随着人口老龄化速度的加快、心血管疾病发病率的上升,心脏疾病尤其是心肌梗死的有效治疗使更多的患者得以生存,但随后慢性心力衰竭患者日趋增多。心力衰竭最终死亡原因主要是进行性心力衰竭加重和／或心脏性猝死（SCD）。     

Long-term incidence of malignant ventricular arrhythmia and shock therapy in patients with primary defibrillator implantation does not differ from event rates in patients treated for survived cardiac arrest

INTRODUCTION: Recent trials have demonstrated benefit of prophylactic defibrillator (ICD) implantation compared to conventional treatment in high-risk patients. However, many patients have rare or no sustained arrhythmias following implantation. Our study addresses the question, whether patients with prophylactic defibrillator implantation have a lower risk for life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) compared to sudden cardiac death (SCD) survivors. METHODS AND RESULTS: Over 7 years we enrolled 245 patients. Occurrence of spontaneous sustained VT/VF resulting in adequate ICD treatment was the endpoint. Incidence, type, and treatment of sustained arrhythmia in 43 previously asymptomatic ICD recipients (group B) were compared to data of 202 survivors of imminent SCD (group A). All patients had severely impaired left ventricular ejection fraction (<45%). Group B patients had long runs (>6 cycles, <30 s) of VT during Holter monitoring and inducible sustained arrhythmia. Incidence of rapid VT and VF (cycle length <240 ms/heart rate >250 bpm) after 4 years (35% in both groups, P = ns) and adequate defibrillator therapies (57% vs 55%, P = ns) were similar in both groups after univariate and multivariate analysis. Cumulative mortality tended to be lower in group B compared to group A, but the difference was not statistically significant. CONCLUSION: During long-term follow-up, incidence of sustained rapid ventricular arrhythmia in prophylactically treated patients is as high as that of SCD survivors. Benefit from defibrillator implantation for primary prevention (group B) appears to be comparable to that for survived cardiac arrest (group A).     

Current status of implantable cardioverter-defibrillator therapy in heart failure

Sudden cardiac arrest is one of the leading causes of death in patients with heart failure (HF). The implantable cardioverter-defibrillator (ICD) is the only evidence-based treatment strategy for patients who have survived a life-threatening ventricular arrhythmic event. Randomized clinical trials have shown that specific subsets of HF patients with ischemic and nonischemic dilated cardiomyopathy benefit from ICD therapy for primary prevention of sudden cardiac arrest. Cardiac resynchronization therapy has become the device-based therapy of choice for improving symptoms and survival in severe HF patients with evidence of ventricular dyssynchrony. This review summarizes the current status of ICD therapy in treating HF patients based on randomized clinical trials and current practice guidelines.     

Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death

BACKGROUND: Cardiac light-chain amyloidosis carries a high risk for death predominantly from progressive cardiomyopathy or sudden death (SCD). Independent risk factors for SCD are syncope and complex nonsustained ventricular arrhythmias. OBJECTIVE: The purpose of this study was to test whether prophylactic placement of an implantable cardioverter-defibrillator (ICD) reduces SCD in patients with cardiac amyloidosis. METHODS: Nineteen patients with histologically proven cardiac amyloidosis and a history of syncope and/or ventricular extra beats (Lown grade IVa or higher) received an ICD. RESULTS: During a mean follow-up of 811 +/- 151 days, two patients with sustained ventricular tachyarrhythmias were successfully treated by the ICD. Two patients underwent heart transplantation, and seven patients died due to electromechanical dissociation (n = 6) or glioblastoma (n = 1). Nonsurvivors more often showed progression of left ventricular wall thickness, low-voltage pattern, ventricular arrhythmias (Lown grade IVa or higher), and higher N-terminal pro-brain natriuretic peptide levels than did survivors. Bradycardias requiring ventricular pacing (VVI 40/min <1%, DDD 60/min 6% +/- 1%) occurred only rarely. CONCLUSION: Patients with cardiac amyloidosis predominantly die as a result of electromechanical dissociation and other diagnoses not amenable to ICD therapy. Selected patients with cardiac amyloidosis may benefit from ICD placement. Better predictors of arrhythmia-associated SCD and randomized trials are required to elucidate the impact of ICD placement in high-risk patients with cardiac amyloidosis.     

Prophylactic implantable cardioverter defibrillator trials: MUSTT, MADIT, and beyond. Multicenter Unsustained Tachycardia Trial. Multicenter Automatic Defibrillator Implantation Trial

MUSTT and MADIT have clearly shown the survival benefit of an implantable cardioverter defibrillator (ICD) in patients with previous myocardial infarction, left ventricular ejection fraction < or = 0.40, and nonsustained ventricular tachycardia (VT), and who have had sustained VT induced at electrophysiology study. Progress in primary prevention of sudden cardiac death (SCD) depends on a concerted effort by clinicians to identify and appropriately treat MUSTT/MADIT-type patients; further research to more precisely define patient subgroups at risk for SCD and the willingness of industry to develop a lower priced ICD for prophylactic use are needed.     

The Midlands Trial of Empirical Amiodarone versus Electrophysiology-guided Interventions and Implantable Cardioverter-defibrillators (MAVERIC): a multi-centre prospective randomised clinical trial on the secondary prevention of sudden cardiac death.

AIMS: MAVERIC was a randomised clinical trial designed to test the possibility of prospectively identifying patients who would benefit most from the implantable cardioverter-defibrillator (ICD) by electrophysiology (EP) study in the context of secondary prevention of sudden cardiac death (SCD) through comparing EP-guided interventions (anti-arrhythmic drugs, coronary revascularization, and ICD) against empirical amiodarone therapy. METHODS: Two hundred and fourteen survivors of sustained ventricular tachycardia (VT), ventricular fibrillation (VF) or SCD were randomized to either treatment strategy, pre-stratified for haemodynamic status at index event, and followed up for a median of 5 years. RESULTS: Of the 106 amiodarone arm patients, 89 (84%) received the drug and 5 (5%) received an ICD after crossing over. Of the 108 EP arm patients, 31 (29%) received an ICD, 46 (43%) received anti-arrhythmic drugs only (mainly amiodarone or sotalol) and 18 (17%) received coronary revascularization but no ICD. No significant differences in survival or arrhythmia recurrence existed between the two treatment arms after 6 years. However, ICD recipients had a lower mortality than non-ICD recipients, regardless of allocated treatment (hazard ratio=0.54, p=0.0391). CONCLUSIONS: Prospective selection of patients to receive the ICD by EP study did not improve survival compared with empirical amiodarone therapy among survivors of VT, VF or SCD, whereas ICD implantation improved survival regardless of allocated treatment. On this basis, routine EP study has no role in the management of such patients, who should be offered empirical ICD therapy according to the results of other secondary prevention ICD trials.     

Sudden cardiac death in nonischemic cardiomyopathy

Sudden cardiac death (SCD) is a major cause of mortality in patients with nonischemic cardiomyopathy (NICM). Identifying patients who are at highest risk for SCD is an ongoing challenge. At present, guidelines recommend the use of an implantable cardioverter-defibrillator (ICD) in patients with NICM with a reduced left ventricular ejection fraction (LVEF) and heart failure (HF) symptoms. Some recent data, however, suggest that ICDs may not increase longevity in this population. Conversely, community-based studies have demonstrated that many at-risk individuals who may benefit from ICD therapy remain unprotected. Current recommendations for ICD implantation are continually debated, justifying comprehensive individualized risk assessment. Various promising techniques for further risk stratification are under evaluation, including cardiac magnetic resonance imaging, electrocardiographic assessment of electrical instability, and genetic testing. However, none of these strategies has been fully adapted into guidelines. Hence, clinical risk stratification practice today depends on LVEF and HF symptoms, which have poor sensitivity and specificity for predicting SCD risk.     

Update on primary prevention implantable cardioverter-defibrillator therapy

Although the death rate from cardiovascular disease has decreased, nearly 2400 Americans die from cardiovascular disease each day (an average of one person every 37 seconds). Sudden cardiac death (SCD) affects individuals in the prime of their lives, with resuscitation rates successful in only a minority of patients, in part due to absent defibrillation by lay responders. After the publication of positive trials, the Centers for Medicare & Medicaid Services approved the implantable cardioverter-defibrillator (ICD) for the primary prevention of SCD. More recently, ICD therapy also has been shown to be effective for the primary prevention of SCD in patients with systolic heart failure, sometimes with the addition of cardiac resynchronization therapy. This article reviews the current status of primary prevention ICD therapy.     

Prevention of sudden cardiac death: lessons from recent controlled trials.

Sudden cardiac death (SCD), presumably because of ventricular tachyarrhythmias, remains one of the major challenges of contemporary cardiology. Major randomized controlled trials conducted in patients with coronary artery disease (CAD) with the aim of primary prevention of SCD are providing insights. Several large-scale studies have demonstrated that treatment with beta-blockers, angiotensin-converting enzyme inhibitors, aldosterone antagonists, and statins results not only in a reduction in all-cause mortality but specifically also in SCD. On top of this optimized pharmacological therapy, implantable cardioverter-defibrillators (ICD) further decrease the risk of overall and SCD mortality in carefully selected patient groups. The sum of these trials indicates, however, that the benefit associated with ICD therapy is most prominent in patients with chronic stable CAD. In contrast, patients early after myocardial infarction derive less benefit from ICD treatment, presumably because of a high competing risk of non-arrhythmic cardiovascular death. Optimized pharmacological therapy, together with the ICD, can substantially improve the prognosis of high-risk CAD patients.     

Is primary antiarrhythmic drug therapy for ventricular arrhythmias obsolete?

Sudden cardiac death (SCD) remains a major public health threat. Patients with aborted SCD have a high incidence of recurrent life-threatening ventricular arrhythmias. Antiarrhythmic drug approaches dominated early attempts to prevent SCD; however, several trials with sotalol and amiodarone revealed an unacceptably high rate of recurrent arrhythmic events. With the advent of the implantable cardioverter defibrillator (ICD), the primary role of antiarrhythmic drug therapy for the secondary prevention of SCD has been called into question. Two recently completed trials, the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial and the Canadian Implantable Defibrillator Study (CIDS), confirm the superiority of the ICD over the best medical therapy for saving lives.     

Implantable device therapy

Sudden cardiac death (SCD) accounts for two-thirds of fatal events related to heart disease. Coronary heart disease and non-ischemic cardiomyopathy are the most common causes of SCD. Data from major randomized trials have consistently shown that therapy with an implantable cardioverter defibrillator (ICD) results in a significant and meaningful effect on survival through a reduction in the risk of SCD in these population. These data have resulted in a marked increase in the application of implantable device therapy in the past 2 decades from secondary prevention with an implantable cardioverter/defibrillator (ICD) in survivors of a cardiac arrest to primary prevention of SCD in asymptomatic patients with ischemic and non-ischemic left ventricular dysfunction, and prevention of symptomatic heart failure progression and death with cardiac resynchronization therapy (CRT), and devices that combine CRT and ICD therapies (CRT-D). However, there are still areas of uncertainty regarding device therapy that include inconsistent benefit in risk-subgroups of patients with low ejection fraction; increased risk of heart failure after life-prolonging ICD therapy, and a considerable rate of device malfunction despite increasing sophistication. In the present review we focus on current data regarding the clinical indications as well as the safety and efficacy of implantable device therapy, including ICD, CRT, and CRT-D.     

The Optimal Timing of Primary Prevention Implantable Cardioverter-Defibrillator Referral in the Rapidly Changing Medical Landscape

The use of implantable cardioverter-defibrillators (ICDs) significantly reduces the risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Current guidelines, which are based on seminal clinical trials published nearly 2 decades ago, recommend that patients be on optimal medical therapy for HF for a minimum of 3 months before referral for prophylactic ICD. This waiting period allows for left ventricular reverse remodelling and improvement in HF symptoms, which may render primary prevention ICD implantation unnecessary. However, medical therapy for HFrEF has significantly evolved since the publication of these landmark trials. Given the plethora of medical therapy options now available for HFrEF, it is appropriate to reassess the duration of this waiting period. In the present review, we examine the landmark randomised trials in primary prevention of sudden cardiac death in patients with HFrEF, summarise the novel medical therapies (sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors, ivabradine, vericiguat, and omecamtiv mecarbil) that have emerged since the publication of those trials, discuss the optimal timing of ICD referral, and review subtypes of nonischemic cardiomyopathy where timing of ICD insertion is guided by alternative criteria. With the steps now needed to optimise medical therapy for HFrEF, in terms of both classes of drugs and doses of each agent, it can easily take up to 6 months to achieve optimisation. Following that, waiting periods of 3 months for ischemic cardiomyopathy and 6 months for nonischemic cardiomyopathy may be required to allow adequate reverse remodelling before reevaluating for ICD implantation.     

Risk stratification in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by myocyte death and fibrofatty replacement mostly in the right ventricle. It is a leading cause of sudden cardiac death (SCD) in individuals under the age of 35 years. The main goal in the treatment of the disease is the prevention of SCD. An implantable cardioverter-defibrillator (ICD) is the only proven life-saving therapeutic option able to improve survival in ARVC patients. This therapy is not free from side effects and it accounts for a relatively high rate of morbidity because of the occurrence of inappropriate ICD interventions and of complications, both at implantation and during the follow-up. In recent years, the approach to ICD implantation has been changing on the basis of new emerging data on risk stratification. The usefulness of ICD implantation for secondary prevention has been definitively proven; the most challenging question is how to treat patients with no history of previous cardiac arrest or hemodynamically unstable ventricular tachycardia (VT). The value of ECG abnormalities, syncope, VT, and right/left ventricular involvement as predictors of SCD has been assessed in different studies with the purpose of better defining risk stratification in ARVC. Nevertheless, in spite of the growing amount of data, primary prevention in ARVC patients remains mostly an individual decision.     

ICD-Therapie

Sudden cardiac death (SCD) remains the leading common cause for overall mortality in the industrialized world. Although prediction of SCD is considered a necessary prerequisite for its effective prevention and therapy, hard criteria for that goal are difficult to identify. A number of clinical trials were conducted to define the role of implantable cardioverter-defibrillators (ICDs) in preventing SCD. In addition to its undisputed value in secondary prevention of SCD, study results have proven a reduction of mortality through ICDs in patients with both ischemic and non-ischemic cardiomyopathy and a reduced left ventricular ejection fraction (EF). To date, national and international guidelines help us to apply standard ICD indications in patients with structural or hereditary heart diseases that are associated with increased SCD risk. Yet we know that our strategies currently in use for selecting patients who require ICD therapy are imperfect and leave a large number of high-risk patients unprotected. Therefore, the best possible risk assessment should be used in each individual case for optimal SCD prevention without unnecessary device implantation.     

Prevention of sudden cardiac death

The problem of sudden cardiac death (SCD) is complex and many questions concerning the pathophysiologic mechanism are still unanswered. At present the only reliable way of recognizing high risk patients is by means of left ventricular dysfunction, measured as LV-EF相似文献   

The use of implantable cardioverter defibrillators for the prevention of sudden cardiac death: a review of the evidence and implications

Sudden cardiac death (SCD) claims approximately 460,000 lives per year in the United States, and half of these deaths occur in people with a history of coronary artery disease. Patients with left ventricular dysfunction and a history of myocardial infarction are at especially high risk. There is now strong evidence from multiple well-designed randomized controlled trials that implantable cardioverter defibrillators (ICDs) save lives when used for both primary and secondary prevention. As indications for ICD implantation have broadened, considerable debate has taken place because of the substantial cost involved in widespread ICD utilization. This article summarizes the epidemiology of SCD, reviews the evidence supporting the use of ICDs in patients with ischemic cardiomyopathy, and explores some of the controversy surrounding ICD utilization that has arisen in the wake of recent trials that have utilized ICDs for the primary prevention of SCD.     

Prävention des plötzlichen Herztodes

The problem of sudden cardiac death (SCD) is complex and many questions concerning the pathophysiologic mechanism are still unanswered. At present the only reliable way of recognizing high risk patients is by means of left ventricular dysfunction, measured as LV-EF ≤35%. The positive predictive accuracy for other non-invasive risk markers is too low. So far, antiarrhythmic drugs have failed to successfully prevent SCD. More than 25 years of clinical experience with the implantable defibrillator (ICD) with its continuous technical improvement has made the ICD the most effective weapon against SCD. Its effectiveness has been demonstrated in many prospective trials and the use of the ICD is fully enclosed within the current guidelines for the prevention of SCD. Guidelines do not, however, replace the physician’s judgement and experience to correctly evaluate the patient’s status. ICD therapy in the primary and secondary prevention of heart failure, which is often accompanied by a high risk of SCD is, however, not justified without guideline-adjusted therapy.     

室性心律失常的治疗及进展

自从认识到心脏骤停作为心脏性猝死的机制具有很高的发生率以来,医学和临床医生一直在追求一种方法来预测及预防这些心血管事件。在室性心律失常患者中已经完成的一些安慰剂对照的抗心律失常药物试验并没有一致地认为抗心律失常药物治疗能够降低总病死率。近几年发表的临床随机试验证明,植入型心脏复律除颤器与传统的抗心律失常治疗相比,可降低高危亚组患者的病死率。然而,在患者中识别致死性室性心律失常的危险性及衡量使用植入型心脏复律除颤器治疗的价-效比已经成为当今的社会医学问题,尤其在美国。室性心律失常的治疗和心脏性猝死预防仍是将来需要关注的问题。