Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease associated with a risk of ventricular tachyarrhythmias and sudden death, especially in young patients. METHODS: We conducted a retrospective multicenter study of the efficacy of implantable cardioverter-defibrillators in preventing sudden death in 128 patients with hypertrophic cardiomyopathy who were judged to be at high risk for sudden death. RESULTS: At the time of the implantation of the defibrillator, the patients were 8 to 82 years old (mean [+/-SD], 40+/-16), and 69 patients (54 percent) were less than 41 years old. The average follow-up period was 3.1 years. Defibrillators were activated appropriately in 29 patients (23 percent), by providing defibrillation shocks or antitachycardia pacing, with the restoration of sinus rhythm; the average age at the time of the intervention was 41 years. The rate of appropriate defibrillator discharge was 7 percent per year. A total of 32 patients (25 percent) had episodes of inappropriate discharges. In the group of 43 patients who received defibrillators for secondary prevention (after cardiac arrest or sustained ventricular tachycardia), the devices were activated appropriately in 19 patients (11 percent per year). Of 85 patients who had prophylactic implants because of risk factors (i.e., for primary prevention), 10 had appropriate interventions (5 percent per year). The interval between implantation and the first appropriate discharge was highly variable but was substantially prolonged (four to nine years) in six patients. In all 21 patients with stored electrographic data and appropriate interventions, the interventions were triggered by ventricular tachycardia or fibrillation. CONCLUSIONS: Ventricular tachycardia or fibrillation appears to be the principal mechanism of sudden death in patients with hypertrophic cardiomyopathy. In high-risk patients with hypertrophic cardiomyopathy, implantable defibrillators are highly effective in terminating such arrhythmias, indicating that these devices have a role in the primary and secondary prevention of sudden death.     

Living after sudden death: A case report of Naxos disease

Naxos disease is a recessive inherited condition with arrhythmogenic right ventricular dysplasia (ARVD) and a peculiar cutaneous phenotype (woolly hair and a palmoplantar keratoderma). Woolly hair appears from birth, palmoplantar keratoderma develops during childhood and cardiomyopathy is clinically manifested by adolescence. Patients present with syncope, sustained ventricular tachycardia or sudden death. We report a case of a 14 year old boy from Spain, who was admitted into our emergency room after being resuscitated from cardiac arrest, secondary to malignant ventricular tachycardia that developed while he was playing basketball.     

Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators

BACKGROUND: The mortality rate among patients with coronary artery disease, abnormal ventricular function, and unsustained ventricular tachycardia is high. The usefulness of electrophysiologic testing for risk stratification in these patients is unclear. METHODS: We performed electrophysiologic testing in patients who had coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. Patients in whom sustained ventricular tachyarrhythmias could be induced were randomly assigned to receive either antiarrhythmic therapy guided by electrophysiologic testing or no antiarrhythmic therapy. The primary end point was cardiac arrest or death from arrhythmia. Patients without inducible tachyarrhythmias were followed in a registry. We compared the outcomes of 1397 patients in the registry with those of 353 patients with inducible tachyarrhythmias who were randomly assigned to receive no antiarrhythmic therapy in order to assess the prognostic value of electrophysiologic testing. RESULTS: Patients were followed for a median of 39 months. In a Kaplan-Meier analysis, two-year and five-year rates of cardiac arrest or death due to arrhythmia were 12 and 24 percent, respectively, among the patients in the registry, as compared with 18 and 32 percent among the patients with inducible tachyarrhythmias who were assigned to no antiarrhythmic therapy (adjusted P<0.001). Overall mortality after five years was 48 percent among the patients with inducible tachyarrhythmias, as compared with 44 percent among the patients in the registry (adjusted P=0.005). Deaths among patients without inducible tachyarrhythmias were less likely to be classified as due to arrhythmia than those among patients with inducible tachyarrhythmias (45 and 54 percent, respectively; P=0.06). CONCLUSIONS: Patients with coronary artery disease, left ventricular dysfunction, and asymptomatic, unsustained ventricular tachycardia in whom sustained ventricular tachyarrhythmias cannot be induced have a significantly lower risk of sudden death or cardiac arrest and lower overall mortality than similar patients with inducible sustained tachyarrhythmias.     

Pathological features of hypertrophic obstructive cardiomyopathy

The macroscopic features of hypertrophic obstructive cardiomyopathy are variable. The most easily recognized picture is of disproportionate and asymmetrical left ventricular hypertrophy with a small ventricular volume. Symmetrical ventricular hypertrophy also occurs and dilatation of the ventricular cavity may lead to a configuration more usually associated with congestive cardiomyopathy. Papillary muscle involvement leads to a bullet shape, often retained even when the ventricle dilates. Eighteen of the hearts showed a distinctive band of fibrous thickening below the aortic valve. This was a mirror image of the free edge of the anterior mitral cusp, had the microscopic features of an endocardial friction lesion, and was clearly the morphological expression of the systolic contact between cusp and septum seen on cineangiography. This band is characteristic of hypertrophic obstructive cardiomyopathy; it was more common in older patients and is of particular diagnostic value in cases with symmetrical hypertrophy, including those with dilated ventricular cavities.Sudden death was the commonest presentation in the younger cases but in several cases over 60 years at death hypertrophic obstructive cardiomyopathy was an incidental necropsy finding.     

A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators

BACKGROUND: Empirical antiarrhythmic therapy has not reduced mortality among patients with coronary artery disease and asymptomatic ventricular arrhythmias. Previous studies have suggested that antiarrhythmic therapy guided by electrophysiologic testing might reduce the risk of sudden death. METHODS: We conducted a randomized, controlled trial to test the hypothesis that electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were randomly assigned to receive either antiarrhythmic therapy, including drugs and implantable defibrillators, as indicated by the results of electrophysiologic testing, or no antiarrhythmic therapy. Angiotensin-converting-enzyme inhibitors and beta-adrenergic-blocking agents were administered if the patients could tolerate them. RESULTS: A total of 704 patients with inducible, sustained ventricular tachyarrhythmias were randomly assigned to treatment groups. Five-year Kaplan-Meier estimates of the incidence of the primary end point of cardiac arrest or death from arrhythmia were 25 percent among those receiving electrophysiologically guided therapy and 32 percent among the patients assigned to no antiarrhythmic therapy (relative risk, 0.73; 95 percent confidence interval, 0.53 to 0.99), representing a reduction in risk of 27 percent). The five-year estimates of overall mortality were 42 percent and 48 percent, respectively (relative risk, 0.80; 95 percent confidence interval, 0.64 to 1.01). The risk of cardiac arrest or death from arrhythmia among the patients who received treatment with defibrillators was significantly lower than that among the patients discharged without receiving defibrillator treatment (relative risk, 0.24; 95 percent confidence interval, 0.13 to 0.45; P<0.001). Neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to electrophysiologically guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy. CONCLUSIONS: Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease.     

Chagas' heart disease in the United States

BACKGROUND AND METHODS. Chagas' heart disease is believed to be rare in the United States, although many persons from countries where the disease is endemic reside here. We performed a retrospective case review and prospective follow-up of 25 patients with Chagas' heart disease and no obstructive coronary artery disease on angiography. RESULTS. The patients mainly presented with symptomatic atrioventricular block, congestive heart failure, anginal chest pain, sudden death averted by resuscitation, or sustained ventricular tachycardia. Of the 25 patients, 18 had been treated for coronary artery disease or idiopathic dilated cardiomyopathy for up to 108 months before the diagnosis of Chagas' disease was considered. The electrocardiograms frequently suggested coronary artery disease. Six of the seven patients who had exercise thallium-perfusion scans had abnormalities suggesting ischemia or infarction. A left ventricular aneurysm was found in 14 of the 25 patients, segmental akinesia or hypokinesia in 5, and diffuse hypokinesia in 3. Programmed ventricular stimulation performed in 13 patients induced sustained ventricular tachycardia in 9 and nonsustained ventricular tachycardia in 2. Actuarial survival (mean +/- SE) after four years for the entire group was 56 +/- 12 percent; it was 32 +/- 16 percent among those with global left ventricular dysfunction, and 78 +/- 14 percent among those without such dysfunction (P = 0.03). Only patients with left ventricular dysfunction or an aneurysm died (four-year survival, 45 +/- 14 percent, as compared with 100 percent for the remaining patients; P = 0.0002). Heart failure and left ventricular aneurysm or dysfunction were the only independent predictors of death. Nine patients required permanent pacemakers. CONCLUSIONS. In the United States, Chagas' heart disease commonly mimics coronary artery disease or idiopathic dilated cardiomyopathy. The prognosis is poor for patients with heart failure or left ventricular aneurysm or dysfunction. The disease may be underdiagnosed in the United States.     

Treatment of malignant ventricular arrhythmias with endocardial resection and implantation of the automatic cardioverter-defibrillator

Although ventricular resection guided by endocardial mapping has been a successful treatment for drug-refractory ventricular arrhythmias, 20 to 30 percent of patients still have postoperative sustained ventricular tachycardia or sudden death. To improve the outcome of the procedure, we implanted an automatic cardioverter-defibrillator in conjunction with endocardial resection in 28 patients, all of whom had had previous myocardial infarctions and between one and five cardiac arrests. There were three perioperative deaths. During follow-up of 8 to 51 months (mean, 25), 4 of the 25 survivors had recurrences of hypotensive ventricular tachycardia, which in all instances were automatically terminated by the implanted device. One patient, whose automatic cardioverter-defibrillator was not functional, died suddenly. We conclude that patients undergoing mapping-directed endocardial resection can be provided with additional protection against recurrent ventricular tachyarrhythmias or sudden death by implantation of an automatic cardioverter-defibrillator.     

Can sudden cardiac death be prevented?

Hypertrophic cardiomyopathy is regarded as the most common cause of sudden cardiac death in young people (including trained athletes). Introduction of implantable cardioverter-defibrillators to the hypertrophic cardiomyopathy patient population represents a new paradigm for clinical practice and perhaps the most significant advance in the management of this disease to date. Implantable defibrillators offer the only proven protection against sudden death by virtue of effectively terminating ventricular tachycardia/fibrillation and, in the process, altering the natural history of hypertrophic cardiomyopathy and providing the potential opportunity of normal or near-normal longevity for many patients. However, targeting the most appropriate candidates for prophylactic device therapy can be complex, compounded by the unpredictability of the underlying arrhythmogenic substrate, absence of a single dominant and quantitative risk marker in this heterogeneous disease, and the historical difficulty in assembling sufficiently powered prospective and randomized trials in large patient populations. Nevertheless, the current risk factor algorithm, when combined with a measure of individual physician judgment, is an effective strategy for identifying high-risk patients. Indeed, prevention of sudden death has now become an integral, albeit challenging, component of overall hypertrophic cardiomyopathy management.     

Sudden unexpected cardiac death—a practical approach to the forensic problem

Sudden cardiac death can usually be resolved by the pathologist into ischaemic heart disease, non-vascular cardiac disease such as aortic stenosis or hypertrophic obstructive cardiomyopathy and infrequently a morphologically normal heart on naked eye examination. When ischaemic heart disease is present one third of cases have a recent occlusive coronary artery thrombosis. Two thirds of patients have coronary stenosis only; the minimum degree of disease reasonably associated with sudden death is one area of 85% stenosis. The majority of patients, however, have multiple areas of stenosis. The predominant causes of non-ischaemic sudden death are severe LV hypertrophy, hypertrophic obstructive cardiomyopathy and the prolapsing mitral valve syndrome. Where the heart and coronary arteries are morphologically normal, review of any previous ECG's, a family history and histological examination of the myocardium and conduction system may reveal a cause or at least allow a reasonable assumption of cardiac arrhythmia to be made. Sudden unexpected death where the circumstances strongly suggest a cardiac cause may pose problems for the pathologist. Ischaemic heart disease (coronary atherosclerosis) is undoubtedly the most frequent cause but even when this is so the detailed pathology is controversial. It is when coronary artery disease is conspicuously absent, often in young individuals previously in good health, that a problem exists. Sudden death in infancy (cot death) is a different entity with its own problems and is not here discussed further.     

Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates

We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members.     

A Case of Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion-triggered syncope and sudden cardiac death. We experienced a case of CPVT in an 11 year-old female patient who was admitted for sudden cardiovascular collapse. The initial electrocardiogram (ECG) on emergency department revealed ventricular fibrillation. After multiple defibrillations, sinus rhythm was restored. However, recurrent ventricular fibrillation occurred during insertion of nasogastric tube without sedation in coronary care unit. On ECG monitoring, bidirectional ventricular tachycardia occurred with sinus tachycardia and then degenerated into ventricular fibrillation. To our knowledge, there has been no previous case report of CPVT triggered by sinus tachycardia in Korea. Therefore, we report the case as well as a review of the literature.     

Angled aorta ("sigmoid septum") as a cause of hypertrophic subaortic stenosis

Review of the hearts of seven patients in whom hypertrophic obstructive cardiomyopathy had been diagnosed by the usual clinical and morphologic criteria revealed diminished angles between the interventricular septa and ascending aortas in three cases. The angles in these three hearts were 90 to 110 degrees, as compared with a mean value of 145 degrees in the other four hearts with hypertrophic obstructive cardiomyopathy and 140 +/- 14 degrees in 55 control hearts. None of the patients with hypertrophic subaortic stenoses and angled aortic roots died of the heart disease, and none had either asymmetric ventricular hypertrophy or evidence of familial cardiomyopathy. It is proposed that in patients with angled aortic roots and left ventricular hypertrophy, subaortic obstruction may develop due to narrowing of the left ventricular outflow tract, resulting in clinical and morphologic findings of hypertrophic obstructive cardiomyopathy. In hearts with angled aortic roots the top of the ventricular septum is tipped toward the mitral valve, rather than tapered toward the aorta, as in normal hearts. This configuration narrows the outflow tract of the left ventricle and can result in systolic anterior motion of the mitral valve, the illusion of asymmetric septal hypertrophy when studied by M-mode echocardiography, a subaortic pressure gradient, and a subaortic endocardial plaque. This less serious form of hypertrophic subaortic stenosis should be distinguished from other forms of hypertrophic obstructive cardiomyopathy.     

The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia

Although electrophysiologic testing accurately delineates abnormalities in patients with fixed cardiac-conduction defects, its sensitivity in identifying transient rhythm disturbances is unknown. We prospectively studied 21 patients who had electrocardiographically documented intermittent atrioventricular block (n = 13) or sinus pauses (n = 8) causing syncope, but whose cardiac rhythm had reverted to normal by the time of referral. There were 14 men and 7 women, with a mean age (+/- SD) of 63 +/- 13 years. Fourteen patients had organic heart disease, and 8 were taking cardioactive medications. Electrophysiologic testing was performed before the implantation of a permanent pacemaker. Only three of the eight patients with documented sinus pauses had abnormalities during their tests that suggested the correct diagnosis (sensitivity, 37.5 percent), including a prolonged sinus-node recovery time in one and carotid-sinus hypersensitivity in two. Three of the eight patients had abnormalities detected that were unrelated to syncope, including atrial flutter, dual atrioventricular nodal pathways, and sustained monomorphic ventricular tachycardia. Of the 13 patients with documented atrioventricular block, only 2 had abnormalities suggesting the correct diagnosis (sensitivity, 15.4 percent). Additional observations unrelated to syncope among these 13 patients included abnormal sinus-node function, atrial flutter, and atrial fibrillation causing hypotension. These preliminary observations suggest that a negative electrophysiologic test in a patient with a normal cardiac rhythm who has experienced syncope does not exclude a transient bradyarrhythmia as a cause of the syncope. Furthermore, electrophysiologic testing may sometimes reveal unrelated rhythm disturbances that may mistakenly be designated as the cause of the syncope.     

The investigation of sudden cardiac death

Pathologists are faced with an increasing complexity in the cardiac diseases that cause sudden natural death in the absence of coronary artery disease. A significant proportion of such natural sudden deaths are due to familial heart muscle disease (cardiomyopathy). The phenotypic characteristics of both hypertrophic cardiomyopathy and arrythmogenic right ventricular dysplasia are wider than previously thought and the hearts may be very close to normal on naked eye examination. Detailed histology of the myocardium is needed to identify such cases. Up to 200 sudden deaths a year in England occur in young, apparently fit individuals in whom toxicology and detailed examination of the heart for structural abnormalities is negative. Genetic defects in ion channels (long QT interval) are now known to be one cause of this phenomenon. In investigating a case of sudden death without cause, a study of the family -- if they wish it -- may be helpful in arriving at a cause.     

Idiopathic hypertrophic subaortic stenosis: detection by thallium 201 myocardial perfusion imaging.

To determine whether thallium 201 myocardial imaging could be used to detect hypertrophic cardiomyopathy, 10 patients with idiopathic hypertrophic subaortic stenosis were studied. Asymmetric septal hypertrophy, an anatomic marker for this disease, was evident on thallium scans in the patients with idiopathic hypertrophic subaortic stenosis, with a ratio of septum to left ventricular free wall of 1.7 cm compared to 1.0 cm in eight normal volunteers, and 1.0 cm in eight patients with concentric left ventricular hypertrophy. Patients with hypertrophic cardiomyopathy also demonstrated apical ventricular wall thickening, and a thicker posterior ventricular free wall in the obstructive in contrast to the nonobstructive form of this disease. Thallium scans of three patients with pulmonary hypertension and secondary asymmetric septal hypertrophy were distinguished from idiopathic hypertrophic subaortic stenosis by marked right ventricular wall thickening. Thus, thallium 201 myocardial perfusion imaging provides a noninvasive method for detection and evaluation of idiopathic hypertrophic subaortic stenosis.     

Longitudinal electrophysiologic assessment of asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern

Although most asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern have a good prognosis, some die suddenly. The mechanism of sudden death is usually ventricular fibrillation, which is triggered by atrial fibrillation with a rapid ventricular response rate. Electrophysiologic testing has been proposed to identify asymptomatic patients who may be at risk for sudden death. Meaningful application of such testing requires a knowledge of whether the electrophysiologic measurements are reproducible over time. Consequently, we performed electrophysiologic studies on two occasions at least 36 months apart (mean +/- SD, 54.7 +/- 14) in 29 asymptomatic patients with the pattern. Twenty-seven patients remained asymptomatic, and sustained supraventricular tachycardia developed in two during the follow-up period. Nine patients (31 percent) lost the capacity for preexcitation and anterograde conduction over the accessory pathway, which produces the Wolff-Parkinson-White pattern. The others had little change in measurements of conduction over the accessory pathway. Patients who lost conduction over the accessory pathway tended to be older (mean +/- SD, 50 +/- 18 vs. 39 +/- 11 years; P = 0.06) than patients who retained preexcitation, and they had longer anterograde effective refractory periods at the first assessment (414 +/- 158 vs. 295 +/- 27 msec; P = 0.003). We conclude that a considerable number of asymptomatic patients with the Wolff-Parkinson-White pattern lose their capacity for anterograde conduction over the accessory pathway. This loss of capacity probably contributes to the low mortality among asymptomatic patients.     

A comparison of electrophysiologically guided antiarrhythmic drug therapy with beta-blocker therapy in patients with symptomatic, sustained ventricular tachyarrhythmias.

BACKGROUND. Antiarrhythmic drug therapy guided by invasive electrophysiologic testing is now widely used in patients with symptomatic, sustained ventricular tachyarrhythmias. METHODS. We conducted a prospective, randomized trial in 170 patients to investigate whether this approach would improve long-term outcome. Patients whose arrhythmia was inducible by programmed electrical stimulation were assigned to treatment with electrophysiologically guided drug therapy based on serial testing (61 patients) or with metoprolol (54 patients). Electrophysiologically guided therapy consisted of serial testing of antiarrhythmic agents to identify the first one that rendered the arrhythmia noninducible. The 55 patients whose arrhythmia was noninducible during the initial electrophysiologic test were also treated with metoprolol. RESULTS. During a mean (+/- SD) follow-up period of 23 +/- 17 months, recurrent, nonfatal arrhythmia occurred in 44 patients and sudden death due to cardiac factors in 27. The incidence of symptomatic arrhythmia and sudden death combined was virtually the same in the two groups with inducible arrhythmia after two years of observation (electrophysiologically guided therapy vs. metoprolol therapy, 46 percent vs. 48 percent). The outcome was more favorable in the patients with noninducible arrhythmia at base line (75 percent had neither adverse event) than in those with inducible arrhythmia who were assigned to metoprolol therapy (P = 0.009 by log-rank test). Only 6 of the 29 patients (21 percent) with inducible arrhythmia that became noninducible during drug therapy had recurrent arrhythmia or sudden death, as compared with 21 of the 32 patients (66 percent) with arrhythmia that continued to be inducible (P less than 0.001). A multivariate regression analysis identified continued inducibility of the arrhythmia as an independent predictor of recurrent arrhythmia or sudden death (relative risk, 7.3; 95 percent confidence interval, 2.3 to 23.2; P less than 0.001). CONCLUSIONS. As compared with metoprolol therapy, electrophysiologically guided antiarrhythmic drug therapy did not improve the overall outcome of patients with sustained ventricular tachyarrhythmias. However, effective suppression of inducible arrhythmia by antiarrhythmic drugs was associated with a better outcome than was lack of suppression.     

遗传性心肌病的临床实践指南

心肌病是一组异质性心肌疾病,可由各种原因(常为遗传因素)引起,能够导致心力衰竭、心律失常和猝死。原发性心肌病包括遗传性肥厚型心肌病、致心律失常右室心肌病、线粒体心肌病、混合性(遗传性及获得性)扩张型心肌病和限制型心肌病、左心室致密化不全以及其他未分类的心肌病。借助基因组学技术,在人群中发现的一些常见突变与疾病的关联已被鉴定。这些突变的体内和体外功能研究为疾病的发生机制和治疗提供了有用的线索。本指南在参考国内外本领域的基础研究、临床研究和其他国家的相关指南共识的基础上,对不同类型遗传型心肌病的表型、诊断、治疗及遗传咨询进行了总结,期望有助于患者临床管理的规范化。     

Serum transforming growth factor-beta1 as a risk stratifier of sudden cardiac death

Sudden cardiac death prematurely claims the lives of some 7 million each year worldwide. It occurs primarily in patients with an underlying structural cardiac abnormality, and regardless of the type of the underlying pathology (heart failure, dilated and hypertrophic cardiomyopathies, myocardial infarction and aging), death is almost always caused by ventricular tachycardia (VT) which rapidly degenerates to ventricular fibrillation (VF). Implantable cardioverter defibrillator is an effective but expensive therapy for preventing SCD, and finding a reasonably specific, sensitive and cost-effective risk stratification tool for patients at high risk of sudden cardiac death will have great clinical utility in preventing premature sudden cardiac death. Increased myocardial fibrosis has been shown to develop in a wide range of cardiac diseases all manifesting increased risk of VT and VF. Clinical and experimental studies attribute a major role for fibrosis in the initiation of VT, VF and sudden cardiac death. Transforming growth factor-beta1 (TGF-beta1) has been shown to promote myocardial tissue fibrosis and perhaps more importantly in cardiac conditions associated with increased myocardial fibrosis are shown to be positively correlated with increased serum levels of TGF-beta1. In the present hypothesis we suggest that monitoring the serum levels of TGF-beta1 may be a cost-effective risk stratifier to identify patients at high risk of sudden cardiac death caused by VT and VF.     

QT dispersion in adult hypertensives

Increased QT dispersion is associated with sudden cardiac death in congestive cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction. Patients with hypertension--in particular, those with left ventricular hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with LVH. One-hundred untreated patients with systemic hypertension and 78 normotensives had QT dispersion measured manually from a surface 12-lead electrocardiogram and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness and left ventricular internal diameter. Office blood pressure was also recorded. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Manual measurement of QT dispersion might be a simple, noninvasive screening procedure to identify those hypertensives at greatest risk of sudden cardiac death in a third-world country.