Sudden cardiac death in patients with nonischemic cardiomyopathy

Sudden cardiac death (SCD) is an important cause of mortality worldwide. Although SCD is most often associated with coronary heart disease, the risk of SCD in patients without ischemic heart disease is well-established. Nonischemic cardiomyopathies, including idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy represent three unique disease entities that have been shown to be highly associated with SCD and ventricular arrhythmias. A variety of risk stratification tools have been investigated, although the optimal strategy remains unknown. Identification of the arrhythmogenic substrate and treatment of ventricular arrhythmias in these subgroups can be challenging. Herein, we aim to discuss the current understanding of the anatomic and electrophysiologic substrate underlying ventricular arrhythmias and highlight features that may be associated with a higher risk of SCD in these 3 conditions.     

Sudden cardiac death in nonischemic cardiomyopathy: Refining risk assessment

Sudden cardiac death (SCD) risk assessment among patients with nonischemic cardiomyopathy (NICM) has been has been less straightforward than for patients with ischemic cardiomyopathy. The common surrogate that has been associated with highest SCD risk for all cardiomyopathies, and which has been universally used to guide implantation of primary‐prevention implantable cardioverter‐defibrillators (ICDs), is left ventricular ejection fraction (LVEF) ≤35%. However, this practice has been called into question, especially in light of recent trials suggesting that ICD treatment may not be of additional survival benefit among those with NICM treated with optimal medical therapy. This Clinical Review attempts to offer refinements to the current practice of SCD risk assessment among patients with NICM, with specific focus on importance of NICM etiology and efforts to identify myocardial scarring and arrhythmogenic substrate, both of which may provide greater information about SCD risk than the LVEF alone. These concepts are illustrated further as they apply to hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis, all of which are increasingly recognized NICM substrates associated with SCD and for which refinements for assessing risk are lacking in conventional guidelines.     

肥厚型心肌病与心源性猝死

肥厚型心肌病是最常见的遗传性心血管疾病,心源性猝死是其最恶劣的并发症,可以在各个年龄段发生。该病为35岁以下青年人和运动员发生心源性猝死的最主要原因。植入式心脏除颤器在预防猝死的发生方面取得了令人瞩目的成果,可以及时终止致命的恶性心律失常,挽救猝死高风险患者的生命。所以,判断哪些患者是心源性猝死的高危人群、哪些患者需进行ICD植入、如何进行危险分层至关重要。现有的危险评估模型仍有很大的局限性,需要更大规模的前瞻性研究及完整的数据采集以对其进行补充完善。     

Sudden cardiac death in hypertrophic cardiomyopathy

Background: Recent identification of mutations in the ß-myosinheavy chain gene (MYH7), a major responsible gene for HCM, hasprovided the opportunity to characterize genotype-phenotypecorrelation in HCM families. In this study we analysed the phenotypicexpression of two ß-myosin heavy chain (ßMHC)mutations in three unrelated HCM families. Methods: Living individuals from three unrelated HCM families(Families 1, 2, and 3) were screened by history, physical examination,electrocardiography, and two-dimensional echocardiography. Bloodwas collected from all individuals for DNA extraction. Polymerasechain reaction (PCR), restriction endonuclease digestion andchemical cleavage were utilized for detection of mutations.All mutations were confirmed by sequence analysis. Results:Identification of mutations: A missense mutation in exon 13of the ßMHC gene (Arg⁴⁰³Gln) was detected in HCM patientsfrom Families 1 and 2. PCR amplification of the exon 13 DNA,followed by Ddel digestion of the PCR product and gel electrophoresis,showed two fragments of 84 and 70 bp in normal individuals andfour fragments of 84, 70, 52 and 32 bp in HCM patients. Sequenceanalysis showed substitution of an adenine for guanine at codingposition 1208. In Family 3, a missense mutation in exon 16 ofthe ßMHC gene (Val⁶⁰⁶Met) was detected in HCM patients.Chemical cleavage of the PCR products showed an uncleaved productof 337 bp in the normal individuals, while in the affected individuals,in addition to the uncleaved product, a 90 bp cleaved productwas also detected, indicating the presence of a mismatch inone allele. Sequence analysis showed substitution of an adeninefor guanine in coding position 1817. Clinical Characteristics: Seven members of Family 1 had HCM,of whom five are alive. One patient died from sudden cardiacdeath (SCD) and another from recurrent cerebral embolL In Family2, 15 individuals had HCM of whom nine have died, seven fromSCD. The mean age at the time of SCD was 33 years. The thirdfamily is comprised of 11 affected individuals and one obligatecarrier, of whom one patient died at age 17 from progressiveheart failure. Two additional individuals in this family havealso succumbed to SCD to age 60. A variety of clinical and echocardiographicmanifestations of HCM were present in each family. Logrank test of Kaplan-Meier survival curves indicates thatArg⁴⁰³Gln mutation was associated with a poor prognosis in HCMfamilies as compared to Val⁶⁰⁶Met (P=0.034). Conclusions: ßMHC mutations despite showing variableclinical and echocardiographic manifestations of HCM are predictorsof survival in HCM families.     

Sudden cardiac death in infancy due to histiocytoid cardiomyopathy

Detailed post-mortem is crucial in infants who die suddenly and without a known cause. We report a rare case of histiocytoid cardiomyopathy with endocardial fibroelastosis, the second case in the world literature. The infant presented with sudden death, but the cardiac histological appearance was initially believed to be caused by Pompes disease.     

Sudden death in dilated cardiomyopathy

The purpose of this review is to examine the potential contribution of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss current treatment options. We performed a search of the MEDLINE database from 1985 to the present and the reference citations of selected articles pertaining to the prognostic significance, management, and pathophysiology of arrhythmias in DCM. A large proportion of patients with DCM die suddenly, most secondary to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The presence and severity of ventricular ectopy may predict risk for sudden death, but the role of electrophysiologic study and signal-averaged electrocardiography in further risk stratifying patients remains uncertain. Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme inhibitors improve overall mortality in congestive heart failure, and the use of direct angiotensin-receptor antagonists is currently being studied. In addition, beta-receptor antagonists appear to improve morbidity and may prove to improve mortality in heart failure as well. Other interventions still under investigation include amiodarone and the implantable cardioverter-defibrillator. The underlying pathophysiology of sudden death in DCM involves primarily ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of improving overall mortality, while further study on the roles for newer drugs and devices is ongoing.     

Sudden cardiac death in isolated right ventricular hypertrabeculation/noncompaction cardiomyopathy

Hypertrabeculation/noncompaction of the myocardium is a rare disorder that involves most commonly the left ventricle of the heart and it has been recognized as a distinct cardiomyopathy by the World Health Organization. However, it is extremely rare for this condition to involve exclusively the right ventricle. We report the cases of three patients who presented with ventricular tachyarrhythmia and sudden cardiac death. They were found to have isolated right ventricular hypertrabeculation/noncompaction on echocardiography. This supports the hypothesis that this condition is highly arrhythmogenic and is associated with high mortality similarly to the left ventricular hypertrabeculation/noncompaction cardiomyopathy.     

Sudden cardiac death

Opinion statement  

Sudden cardiac death

SCD continues to be an important cause of death and morbidity. Despite expanding insight into the mechanisms causing SCD, the population at high risk is not being effectively identified. Although there is still much to do in the management phase of SCD (predicting the efficacy of various therapies), recent clinical trials have helped define the relative risks and benefits of therapies in preventing SCD. Trials are underway to determine whether treating other patient populations, including asymptomatic patients after MI, will improve survival rate. The approach to reducing mortality rate will always be multifaceted; primary prevention of coronary artery disease and prompt salvage of jeopardized myocardium are 2 important aspects of this approach. In addition to interventions for MI, such as myocardial revascularization when indicated, simple and easily administered therapies that are likely to remain the most effective prophylactic interventions are aspirin, ACE inhibitors, beta-blockers, and cholesterol-lowering agents. However, the MADIT and AVID data clearly demonstrate a role for ICD therapy in a subgroup of patients who have VT/VF and are at risk of cardiac arrest. Even though the absolute magnitude of benefit associated with ICDs is still to be determined, the AVID study and other recent reports provide convincing evidence that patients who have VT/VF fare better with ICDs than with antiarrhythmic drug therapy. For the high-risk population described in this article, in addition to aggressive anti-ischemic and heart failure therapy, ICDs are now a mainstay of life-saving treatment. Still to be surmounted is the challenge of identifying patients who have nonischemic substrates and of providing them with the appropriate therapy. Guided by genetic studies and new insight into the mechanisms of such problems as congenital long QT syndrome, life-saving and life-enhancing therapies may soon be available for the management of SCD.     

Sudden cardiac death

Opinion statement Sudden cardiac death is often due to a ventricular arrhythmia. When a patient presents with a malignant arrhythmia unrelated to a transient reversible cause, there is a high probability of recurrent arrhythmia and sudden death. Clinical trials have shown a uniform survival benefit from implantable cardioverter-defibrillator (ICD) therapy in survivors of a malignant arrhythmia when compared with drug therapy. However, only 1% to 5% of patients survive an out-of-hospital cardiac arrest, emphasizing the need for primary prevention of sudden death. Clinical trial data available in this regard are largely limited to patients with coronary artery disease (CAD). Mortality can be reduced by the ICD in patients with CAD and depressed left ventricular ejection fraction (LVEF) less than 30%. If left ventricular function is only moderately depressed (LVEF between 30% and 40%), the presence of nonsustained ventricular tachycardia with inducible ventricular arrhythmia at electrophysiologic testing identifies patients who benefit from an ICD. The role of the ICD in primary prevention of sudden death in patients with nonischemic dilated cardiomyopathy is less clear at this time. Preliminary data indicate that the presence of heart failure symptoms in this population increases risk of sudden death that can be prevented by an ICD. Antiarrhythmic drugs have little role in prevention of sudden death; however, drugs that block the effects of β-adrenergic stimulation, angiotensin, and aldosterone reduce mortality partly through their salutary effects on sudden death. Finally, a number of inherited defects of genes coding for ion channels, contractile sarcomeric proteins, and cell-to-cell junction proteins can result in primary electrical abnormalities and sudden death. The ICD is effective for secondary prevention, but its role in primary prevention is controversial and should be based on individual risk factors.     

心脏性猝死

心脏性猝死（sudden cardiac death，SCD）是指由各种心脏原因引起的自然死亡。发病突然、进展迅速，死亡发生在症状出现后1h内。患者发生猝死事件前可以有心脏疾病表现，但猝死的发生具有无法预测的特点。发生心脏骤停的患者能被成功复苏的机会很小，美国约为15％，而大多国家仅为0—5％。因为绝大多数心脏骤停发生在医院外，不能得到有效的快速治疗干预（如初步的紧急心肺复苏术），仅有发生在医院内或有幸经过初步抢救治疗并及时送至急诊室的心脏骤停患者，有机会得到有效治疗而幸存。因此SCD具有突发、迅速、不可预料和病死率高的特征，是直接危及人们生命的一大杀手。     

Sudden cardiac death

Most sudden deaths in industrial nations are the result of underlying coronary artery disease. Longitudinal studies have demonstrated that the percent of all coronary events presenting as sudden death increases with age in both men and women. Relative weight is another important risk factor; the age-adjusted rate of sudden cardiac death for the upper weight tercile in the Framingham study was over 2 times higher for men and 3 times higher for women than the rate for the lower weight tercile. Most patients who die suddenly initially experience ventricular tachycardia that subsequently degenerates into ventricular fibrillation. Patients with a high risk of sudden cardiac death include: survivors of myocardial infarction with left ventricular dysfunction or complex ventricular ectopy, or both; survivors of out-of-hospital cardiac arrest, particularly when the event is not associated with an acute myocardial infarction; patients with recurrent ventricular tachycardia; and patients with dilated congestive cardiomyopathy, particularly when associated with ventricular ectopy. Reducing the risk of sudden death in these patients remains a major challenge.     

Sudden cardiac death and the role of device therapy in dilated cardiomyopathy

Both nonischemic and ischemic dilated cardiomyopathy are associated with an increased risk of sudden cardiac death, most commonly as a result of ventricular tachyarrhythmias. The pathophysiology of sudden death is complex and results from the interplay of scarred myocardium with physiologic and environmental triggers. Clinical trials completed within the past decade have clarified the role of implantable defibrillators in prolonging survival and have expanded the indications for the use of these devices in patients with heart failure. This article examines the pathophysiology of sudden cardiac death and reviews the clinical trials that have defined the role of device therapy in current practice.     

Sudden cardiac death in familial hypertrophic cardiomyopathy. Identification of high-risk patients

Hypertrophic cardiomyopathy (HCM) is a relatively frequent, genetically determined primary cardiomyopathy, characterized by most often asymmetric hypertrophy of the ventricular septum with or without systolic obstruction of the left ventricular outflow tract. HCM is a genetically heterogeneous disease, with 12 different disease-causing genes beeing indentified to date. Histologically the disease is characterized by hypertophy and disarray of myofibrils as well as by an increase in myocardial fibrosis. Clinically, these changes may lead to palpitations, dyspnoe on exertion, and/or angina pectoris. However, they also lead to an increased propensity to the development of severe ventricular tachyarrhythmias and sudden cardiac death. The incidence of sudden death is significantly increased in HCM, particularly in affected young subjects. Risk stratification in HCM should include a complete clinical-cardiological evaluation that should also consider new diagnostic features, e. g. MR imaging. Major risk factors for sudden cardiac death include a survived cardiac arrest (ventricular fibrillation), non-sustained and sustained ventricular tachycardia, a history of premature familial sudden death, unexplained syncope, an abnormal blood pressure response on exercise, and left ventricular thickness greater than or equal to 3 cm. Ideally, risk stratification should also include genetic testing, since some gene mutations seem to be associated with a higher risk for sudden cardiac death than others. However, genetic testing in HCM in not yet available on a routine basis. The implantation of a cardioverter/defibrillator is first-line therapy in patients with documented ventricular tachycardia/fibrillation or patients who have survived sudden cardiac death. These devices also play an important role in the primary prevention of sudden cardiac death in HCM. Algorithms and scores are available to estimate the risk of sudden death, however, the decision to implant a cardioverter/defibrillator remains an individual decision in every single patient.     

Sudden death prevented in hypertrophic cardiomyopathy

The most common cause of sudden cardiac death in individuals aged less than 35 years, including competitive athletes, is the inherited disorder hypertrophic cardiomyopathy (HCM). Until recently, no therapeutic intervention had been identified to prevent sudden death in HCM. This case report highlights the role of the implantable cardioverter defibrillator (ICD) in preventing sudden death in patients with HCM. The report highlights the importance of risk stratification in patients with HCM in order to identify those individuals who would most likely benefit from ICD therapy. The ICD implantation is now the treatment of choice in preventing sudden death in selected (highest risk) populations with HCM. In the future, understanding the molecular basis of sudden death in HCM may identify potential new gene-based therapeutic strategies.