A Primer on Arrhythmias in Patients with Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy are at risk of atrial and ventricular arrhythmias, yet treatment options for these patients are made almost solely by extrapolation from patients with other diseases. Heart block may be seen spontaneously but is especially prevalent following septal reduction strategies. Atrial fibrillation is the most common arrhythmia in patients with hypertrophic cardiomyopathy. The onset of atrial fibrillation often represents a turning point clinically for patients, marked by substantial functional deterioration and morbidity. Sudden cardiac death is the most common cause of death in the young patient, but still contributes to mortality in older patients. Major risk factors for sudden cardiac death include resuscitated sudden cardiac death, marked hypertrophy, syncope, and family history of sudden cardiac death due to hypertrophic cardiomyopathy. Minor risk factors for sudden cardiac death include nonsustained ventricular tachycardia, and hypotensive response to exercise. Emerging possible risk factors include atrial fibrillation, myocardial ischemia, left ventricular outflow tract obstruction, genetic mutations, left ventricular apical aneurysms, myocardial fibrosis, and end stage disease.     

Ventricular arrhythmias, sudden death, and prevention in patients with hypertrophic cardiomyopathy

Sudden unexpected death, often occurring in young asymptomatic patients, is the most devastating facet of the natural history of hypertrophic cardiomyopathy (HCM). It appears to be the consequence of primary ventricular tachyarrhythmias arising in an electrically unstable myocardial substrate characterized by disorganized cellular architecture, ischemia, cell death, and replacement scarring. Although identification of the HCM patient subset at high risk for a catastrophic event with precision continues to present challenges, treatment strategies for the prevention of sudden death are now available. In particular, the implantable cardioverter-defibrillator has a high degree of efficacy in sensing and terminating potentially lethal ventricular tachyarrhythmias and a life-saving role in both the primary and secondary prevention of sudden cardiac death in HCM.     

Die arrhythmogene rechtsventrikuläre Kardiomyopathie

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disorder that is characterized by localized or diffuse atrophy of predominantly right ventricular myocardium with subsequent replacement by fatty and fibrous tissue. Arrhythmias of right ventricular origin are the main clinical manifestation. Affected patients present with ventricular premature beats and nonsustained or sustained ventricular tachycardia demonstrating a left bundle branch block pattern. However, since ventricular tachycardia may also degenerate into ventricular fibrillation, sudden death may be the first manifestation of ARVC.In recent years, ARVC has been more and more recognized as an important and frequent cause of ventricular tachyarrhythmias and sudden cardiac death, particularly in young patients and athletes, with apparently normal hearts. Evidence of the disease is found in 30-50% of family members. ARVC is a genetically heterogeneous disease.The diagnosis is based on electrocardiographic abnormalities and the identification of regional or global right ventricular dysfunction and fibrolipomatosis. Although several potentially causative genes have been identified, currently, genetic testing is not part of the routine diagnostic work-up.An implantable cardioverter-defibrillator is indicated in selected high-risk patients with ARVC (i. e., patients with life-threatening ventricular tachycardia or survivors of sudden cardiac death). The clinical course of the disease is often characterized by progression. In individual patients heart transplantation may become necessary.     

Clinical and pathological analysis of sudden coronary death in hospitalized elderly patients]

Forty-five hospitalized elderly patients with coronary heart disease who died suddenly within 6 hours after the onset of symptoms were analyzed clinically and pathologically and summarized as following. (1) All the cases showed abnormal ST segments or T waves on ECG. (2) Various degrees of cardiac dysfunction were found clinically in all the patients. (3) Pathological examination of 31 cases revealed serious coronary atherosclerosis. New myocardial necrosis and/or multiple myocardial scars existed in about two-thirds of the patients. Based on these findings and characteristics, it is speculated that sudden coronary death in the elderly patients is caused by imbalance between oxygen supply and demand in the myocardium or deterioration of the cardiac function, which may result in fatal ventricular arrhythmia. Therefore, the prevention of sudden coronary death in the elderly patients should be focusing on reduction of myocardial ischemia, improvement of myocardial metabolism and protection of cardiac function.     

Risk stratification and prevention of sudden death in hypertrophic cardiomyopathy

Sudden unexpected death, often occurring in young, asymptomatic patients, is the most devastating facet of the natural history of hypertrophic cardiomyopathy, and appears to be the consequence of primary ventricular tachyarrhythmias arising in an electrically unstable myocardial substrate characterized by disorganized cellular architecture, ischemia, cell death, and replacement scarring. Although precise identification of all hypertrophic cardiomyopathy patients at high risk for a catastrophic event is a clinical challenge, effective treatment strategies for the prevention of sudden death with the implantable cardioverter-defibrillator are now available.     

冠心病猝死的相关因素分析

目的探讨冠心病患者心脏性猝死的发生率及其相关因素。方法回顾分析46例冠心病患者住院期间发生心脏性猝死的有关临床资料,男性32例,女性14例,年龄38-83（49．5±10．7）岁。收集患者的诱因、心电图（ECG）、超声心动图、动态心电图、X线胸片、心电监护、电解质等资料,根据患者相关项目逐项进行分析。结果46例猝死患者占同期冠心病总住院数的2．2％。多数发生猝死的冠心病患者存在一定高危因素,电解质紊乱、Lown3-5级室早、高度房室传导阻滞、束支传导阻滞、心脏扩大、左室肥厚、心功能不全、持续心肌缺血等因素均可触发致命性心律失常;猝死起始的ECG类型及其演变过程多有一定规律性。结论冠心病患者的心脏性猝死发生率为2．2％。冠心病患者发生猝死与电解质紊乱、Lown3-5级室早、高度房室传导阻滞、束支传导阻滞、心脏扩大、左室肥厚、心功能不全、持续心肌缺血等高危因素密切相关。有效控制危险因素能大大降低冠心病猝死发生率。     

A perspective on ventricular arrhythmias: patient assessment for therapy and outcome

Clinical management of patients with ventricular arrhythmias continues to evolve. It is generally accepted that patients with sustained ventricular tachyarrhythmias (ventricular tachycardia [VT] or fibrillation) require treatment. It is also generally accepted that patients with frequent or complex ventricular ectopy or nonsustained VT, in the absence of underlying heart disease, do not require treatment unless relief of symptoms is warranted. Whether patients with frequent or complex ventricular ectopy or nonsustained VT require treatment in the presence of underlying organic heart disease remains uncertain. The concern is that these ventricular arrhythmias may be a precursor for sustained, potentially life-threatening ventricular tachyarrhythmias. Available data suggest that patients with underlying heart disease, particularly coronary artery disease and a previous myocardial infarction, who manifest frequent or complex ventricular ectopy or nonsustained VT are at increased risk for sudden cardiac death. However, no studies have shown that treatment of these arrhythmias will affect outcome. Data are accumulating to suggest that use of the principles of risk stratification permits identification of patients at very high risk for developing sustained ventricular tachyarrhythmias. Carefully designed clinical trials are required before one can provide firm guidelines for the management of these patients. Nevertheless, when several risk factors for sudden cardiac death (e.g., abnormal ejection fraction, a late potential on a signal-averaged electrocardiogram, and frequent or complex ventricular ectopy or nonsustained VT) are present in a patient, especially after a recent myocardial infarction, invasive electrophysiologic testing may help identify those who need treatment (sustained VT is inducible) and those who do not (no sustained VT is inducible).     

Inflammation of the myocardium as an arrhythmia trigger

In patients with acute or chronic myocarditis, arrhythmias are a common and often the only clinical symptom in the natural course of the disease. The potentially malignant tachy- and bradyarrhythmias are of particular significance in the differential diagnosis of sudden cardiac death in myocarditis. Factors responsible for the increased incidence of cardiac arrhythmias are structural changes, parameters of ventricular dynamics and vascular changes. On the one hand, inflammatory processes in the cardiac myocytes and interstitium can lead directly to fluctuations in membrane potential. Fibrosis and scarring of the myocardial tissue and secondary hypertrophy and atrophy of the myocytes favor the development of ectopic pacemakers, late potentials and reentry as a result of inhomogeneous stimulus conduction. Furthermore, parameters of ventricular dynamics such as increased wall tension, increased myocardial oxygen consumption and diminished coronary reserve in the case of disturbed systolic or diastolic left ventricular function also contribute to the increased incidence of arrhythmias. Lastly, vascular factors can further increase the arrhythmogenicity of the inflamed myocardium through the disturbance of micro- and macrovascular perfusion and the resulting myocardial ischemia. Non-invasive rhythmological evaluation by 24 h Holter ECG, measurement of ventricular late potentials and heart rate variability can be used for orienting risk stratification of the at-risk patient with myocarditis. Programmed atrial and ventricular electrophysiological stimulation also has a relatively high predictive value for spontaneous ventricular tachyarrhythmias. It should be emphasized that, at the present time, optimal electrophysiological parameters with a high predictive value do not exist. In a selected patient population, immunosuppressive therapy in addition to conventional antiarrhythmic therapy can lead to the reduction or complete suppression of spontaneous and inducible arrhythmias. Nevertheless, in the interim, further precautionary antiarrhythmic measures such as serial antiarrhythmic treatment, VT ablation and ACID implantation are necessary in patients with malignant cardiac arrhythmias. Right ventricular myocardial biopsy for demonstration or exclusion of myocarditis is an important additional examination which can improve the differential diagnosis and treatment of patients with cardiac arrhythmias of unclear etiology.     

Sudden death in patients with hypertrophic cardiomyopathy: Characterization of 26 patients without functional limitation

Sudden death is a recognized complication in symptomatic patients with hypertrophic cardiomyopathy. However, its occurrence in patients with no or transient previous cardiac symptoms presents a particularly challenging diagnostic and therapeutic dilemma. Therefore, 26 patients with hypertrophic cardiomyopathy whose death was the first definitive manifestation of cardiac disease were evaluated. Their ages ranged from 8 to 49 years (mean 18) and 23 were less than 25 years of age; 19 were male and 7 female. Of the 26 patients, 13 died during or immediately after moderate or severe physical exertion. Of 12 patients with previous cardiac catheterization, 6 had no or a small left ventricular outflow tract gradient under basal conditions and 6 had an outflow gradient of 50 mm Hg or greater. Left ventricular end-diastolic pressure was elevated in nine patients, and the ventricular septum was moderately to severely thickened (17 mm or more) in all patients. The electrocardiogram was abnormal in all 19 patients studied before death. Thus, sudden death may be the first definitive manifestation of cardiac disease in some patients with hypertrophic cardiomyopathy. Although the effects of patient selection in this study group cannot be excluded, sudden death was common in children and young adults and was often related to physical exertion; each patient showed a distinctly abnormal electrocardiogram and moderate to severe ventricular septal thickening.     

Arrhythmogenic right ventricular disease

In patients with syncope, ventricular tachyarrhythmias, and sudden death, in the absence of coronary artery disease or dilative and hypertrophic cardiomyopathy, arrhythmogenic right ventricular disease is a common underlying heart disease. It is marked by ventricular tachyarrhythmias of left bundle branch block pattern, often induced by exercise; negative T-waves in the right precordial leads of the surface-ECG, and localized or diffuse right ventricular contraction abnormalities detected by various imaging techniques in a young, apparently healthy population. Congenital disposition with progressive fibrous and lipomatous tissue infiltration of the right ventricular myocardium with hypertrophy and degeneration of surviving myocytes is the pathogenetic factor leading to modification of conduction and resulting in the development of arrhythmogenic zones. This review contains the current knowledge about arrhythmogenic right ventricular disease on the basis of our own experience, and also a review of the literature. Controversial hypotheses concerning etiology and prognosis are discussed. Variant forms and stages of the disease are described, taking differential diagnostic aspects into consideration. Non-invasive and invasive diagnostic methods are evaluated with regard to their diagnostic accuracy, feasibility, and limitations. Pharmacological and alternative therapeutic concepts are presented, including catheter ablation and surgical intervention.     

Pathological view of sudden cardiac death.

The common cause of sudden cardiac death is ischaemic heart disease. Such patients may have an occlusive recent thrombosis in a major coronary artery but the largest group has no recent occlusion. Comparison of such patients without occlusion with non-cardiac death control hearts suggests that an area of stenosis of 85 per cent is the best discriminating level. Most subjects who die of ischaemic heart disease suddenly have this degree of stenosis in two or three major arteries. Non-ischaemic sudden cardiac death occurs in hypertrophic obstructive cardiomyopathy and in severe left ventricular hypertrophy particularly from aortic valve stenosis. When the heart is macroscopically normal, review of previous electrocardiograms is the most helpful guide and may disclose conditions such as a long QT interval or pre-excitation. When no such data are available examination of the conduction system histologically may be helpful but is often non-specific. Use of the term "cardiomyopathy" by pathologists to cover all non-ischaemic sudden cardiac death is clinically misleading.     

Cardiac levels of norepinephrine, dopamine, serotonin and histamine in Chagas' disease.

Extraction and measurement of biogenic amines (norepinephrine, dopamine, serotonin and histamine) were carried out on human ventricular myocardium obtained from autopsies of individuals divided in the three following groups: chronic Chagas' heart disease (with congestive heart failure: 16 cases, and with sudden and unexpected death: 13 cases); hypertensive heart disease (12 cases); and control patients (with no heart disease: 12 cases). The myocardial samples were obtained from the free walls of left and right ventricles and from the apex. A significant depletion of norepinephrine was detected in those with congestive failure. A poorly elevated level of dopamine was also seen in right ventricular and apical myocardium from those with failure. Left ventricular and apical concentration of serotonin were significantly elevated in the presence of hypertensive heart disease. The most important findings were obtained with histamine, which is increased in both groups of Chagasic patients. We believe that the approach here reported may provide useful informations on the pathogenetic mechanisms, thus far poorly understood, of chronic Chagas' heart disease.     

Sudden cardiac death: can individual risk be predicted?]

Only 30-40% of all victims of sudden cardiac death could so far be classified as risk patients during their lifetime. Risk factors for sudden death have little predictive value in an asymptomatic population: for example, the typical risk profile for the presence of coronary heart disease and changes in the surface-ECG at rest and especially in the surface-ECG under stress. Usually, the victims of sudden cardiac death among top performance athletes have been suffering from a heart disease of which they knew nothing beforehand: below 40 years of age, mostly from hypertrophic cardiomyopathy; beyond 40, predominantly from coronary heart disease. Among the heart diseases, sudden cardiac death is the cause of death most often in hypertrophic cardiomyopathy, in dilatative cardiomyopathy and in certain types of coronary heart disease. Notwithstanding the employment of fully update cardiological diagnostics the risk patients cannot be identified with reliable precision among those suffering from these diseases. It is only clinically manifest persistent ventricular tachycardia or successful reanimation in case of ventricular fibrillation that will definitely pinpoint the patient as being at risk of sudden cardiac death also in the future.     

Sudden death and hypertrophic cardiomyopathy: a review

Hypertrophic cardiomyopathy is a genetic disease that affects the cardiac sarcomere, resulting in myocardial hypertrophy and disarray. Affected patients have a predisposition for malignant ventricular tachyarrhythmias and, consequently, sudden cardiac death. With the availability of therapeutic measures that prevent sudden death, the identification of high-risk patients is now of greater importance. Clinical risk factors for sudden death (ie, age, syncope, family history of sudden cardiac death, cardiac arrest survivor, nonsustained ventricular tachycardia and abnormal blood pressure response to exercise) have been identified. The clinical electrophysiological study is of limited use for stratifying these patients. More recently, increased attention has been given to the degree of echocardiographically documented left ventricular hypertrophy and prognostically significant genetic mutations. Once a high-risk patient is identified, prophylactic treatment is warranted. For this purpose, amiodarone has been supplanted by the implantable cardioverter-defibrillator. Implantable cardioverter-defibrillator treatment appears to reduce the risk of sudden cardiac death in both primary and secondary prevention settings. Thus, tools are now available to identify and treat high-risk patients with hypertrophic cardiomyopathy.     

Arrhythmias in heart failure: current concepts of mechanisms and therapy

About one half of deaths in patients with heart failure are sudden, mostly due to ventricular tachycardia (VT) degenerating to ventricular fibrillation or immediate ventricular fibrillation. In severe heart failure, sudden cardiac death also may occur due to bradyarrhythmias. Other dysrhythmias complicating heart failure include atrial and ventricular extrasystoles, atrial fibrillation (AF), and sustained and nonsustained ventricular tachyarrhythmias. The exact mechanism of the increased vulnerability to arrhythmias is not known. Depending on the etiology of heart failure, different preconditions, including ischemia or structural alterations such as fibrosis or myocardial scarring, may be prominent. Reentrant mechanisms around scar tissue, afterdepolarizations, and triggered activity due to changes in calcium metabolism significantly contribute to arrhythmogenesis. Furthermore, alterations in potassium currents leading to action potential prolongation and an increase in dispersion of repolarization play a significant role. Treatment of arrhythmias is necessary either because patients are symptomatic or to reduce the risk for sudden cardiac death. The individual history, left ventricular function, electrophysiologic testing, and the signal-averaged ECG give useful information for identifying patients at risk for sudden cardiac death. The implantable cardioverter defibrillator (ICD) has evolved as a promising therapy for life-threatening arrhythmias. A potential role may exist for antiarrhythmic drugs, mainly amiodarone. There is growing evidence that patients with sustained VT or a history of resuscitation have the best outcome with ICD therapy regardless of the degree of heart failure. Many of these patients require additional antiarrhythmic therapy because of AF or nonsustained VTs that may activate the device. Catheter ablation or map-guided endocardial resection are additional options in selected patients but seldom represent the only therapeutic strategy.     

高血压性心肌肥厚相关信号通路的研究进展

高血压是目前世界范围内严重威胁人类健康的公共卫生问题。高血压患病率高、治愈率低是常见问题。因为长期的高负荷状态,心肌会出现肥厚,导致心肌功能的衰退,出现高血压性心脏病。其次可以出现高血压性的脑损害,比如说脑卒中、脑溢血及一过性脑缺血等,因此心肌肥厚的产生与高血压则密不可分。心肌肥厚是心肌细胞在多种刺激下发生失代偿反应,最终导致心力衰竭甚至猝死,严重影了高血压的治疗和预后,也使得心肌肥厚迁延不愈。因此,作者查阅大量近年中外文献总结并探究了高血压性心肌肥厚的相关信号通路,这些分子学机制对于临床用药和治疗,发掘疾病的病因,阐释发病的根本具有深远影响。     

Triggers of transient myocardial ischemia: circadian variation and relation to plaque rupture and coronary thrombosis in stable coronary artery disease

The phenomenon of transient myocardial ischemia is common in patients with stable coronary disease and appears to be due both to increases in myocardial demand and to episodic coronary vasoconstriction. The circadian variation of transient ischemic episodes closely parallels the circadian variation of acute coronary syndromes associated with plaque rupture, such as myocardial infarction and sudden death. These concordant temporal patterns of transient ischemia, myocardial infarction and sudden cardiac death probably represent independent manifestations stemming from the consequences of increased sympathetic activity.     

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.     

Arrhythmogenic right ventricular cardiomyopathy: three cases

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare disease characterized by replacement of myocardium with fibrofatty tissue. It mainly involves the right ventricle (RV) and causes abnormal RV performance. ARVC is the most common cause of sudden cardiac death in young Italian athletes because it induces malignant ventricular tachyarrhythmias. Clinical manifestations of ARVC may be different between Chinese and Western patients. In this paper, we share our experience of the clinical manifestations of ARVC and review previous reports of ARVC.     

Long-term outcome of pharmacological and nonpharmacological treatment for ventricular arrhythmias

Recent advances of nonpharmacological therapy such as catheter ablation and implantable cardioverter defibrillator and lessons from the Cardiac Arrhythmia Suppression Trial(CAST) have changed the strategy for ventricular arrhythmias. The safety and efficacy of radiofrequency catheter ablation of symptomatic sustained monomorphic ventricular tachycardia without structural heart disease has made ablation the firstline curative therapy. In idiopathic ventricular fibrillation such as Brugada syndrome, an implantable cardioverter defibrillator is the most effective treatment to prevent sudden cardiac death. In patients with asymptomatic ventricular tachyarrhythmias in heart failure, class I antiarrhythmic drugs should be avoided due to proarrhythmic and negative inotropic effects that may be responsible for increased mortality in some trials. In such patients, amiodarone and beta-blocker may reduce sudden cardiac death. For patients with sustained ventricular tachycardia or ventricular fibrillation in heart failure, amiodarone or implantable cardioverter defibrillator should be considered. In comparison with amiodarone, implantable cardioverter defibrillator markedly reduced sudden death in ventricular tachycardia and ventricular fibrillation survivors in Antiarrhythmics Versus Implantable Defibriltors(AVID). Although better patient selection and clarification of mapping criteria improved the successful ablation rate in patients with structural heart disease, candidates of ablation are few. In patients with extensive structural heart disease, multiple ventricular tachycardias are often present. Catheter ablation of a single ventricular tachycardia may be only palliative. Therefore, implantable cardioverter defibrillator is the most effective treatment to prevent sudden cardiac death, with amiodarone and ablation as the adjunctive therapy to prevent frequent ventricular tachycardia. Furthermore, an implantable cardioverter defibrillator improved survival in selected patients with depressed ventricular function after myocardial infarction, who also have nonsustained and inducible sustained ventricular tachycardia in Multicenter Automatic Defibrillator Implantation Trial(MADIT) and Multicenter Unsustained Tachycardia Trial(MUSTT).