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.     

Association of heart rate variability with arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events. METHODS AND RESULts: We studied 30 consecutive patients (17 males; 45.4 ± 18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19 ± 7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039). CONCLUSIONS: Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events.     

Wearable cardioverter defibrillator: Bridge or alternative to implantation?

The implantable cardioverter-defibrillator(ICD) is effective to prevent sudden cardiac death(SCD) in selected patients with heart disease known to be at high risk for ventricular arrhythmia. Nevertheless, this invasive and definitive therapy is not indicated in patients with potentially transient or reversible causes of sudden death, or in patients with temporary contraindication for ICD placement. The wearable cardioverter defibrillator(WCD) is increasingly used for SCD prevention both in patients awaiting ICD implantation or with an estimated high risk of ventricular arrhythmia though to be transient. We conducted a review of current clinical uses and benefits of the WCD, and described its technical aspects, limitations and perspectives.     

Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death and ventricular tachyarrhythmias in young, apparently healthy individuals and athletes. Myocardial atrophy with subsequent fibrofatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness which are prerequisites for reentrant ventricular tachyarrhythmias.Patients affected with ARVC should be excluded from competitive sports and vigorous training. To provide optimal treatment, a detailed diagnostic evaluation and risk stratification are mandatory. Tailored treatment strategies aim at the suppression or effective termination of recurrent ventricular tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy, catheter ablation, or implantation of a cardioverter defibrillator (ICD).Antiarrhythmic drugs may be used as a stand-alone treatment to suppress ventricular tachycardia (VT) recurrences in patients with ARVC and low risk of sudden death. Sotalol (preferred) or amiodarone in combination with -blockers showed the highest efficacy rates. In patients at higher risk, an ICD should be implanted and antiarrhythmic drugs be used only as an adjunct to prevent or suppress frequent VT recurrences and ICD discharges.Catheter ablation using conventional or electroanatomic mapping techniques yields good acute results for eliminating the targeted arrhythmia substrate. However, during the progressive long-term course of ARVC, VT recurrences from new arrhythmia foci are frequent and therefore limit the curative value of catheter ablation. In patients with frequent VT recurrences and ICD discharges, however, catheter ablation plays an important role as a palliative and adjunctive treatment option for arrhythmia suppression.ICD therapy has been increasingly used for secondary and also primary prevention of sudden death in patients with ARVC. In secondary prevention, the ICD has shown to improve the long-term prognosis of patients at high risk of sudden death by effective termination of life-threatening recurrences of ventricular tachyarrhythmias. However, adequate lead placement may be difficult and lead-related complications during long-term follow-up must be taken into account. The role of ICD therapy for primary prevention of sudden death in ARVC is not yet adequately defined.Ongoing international registries will provide important additional data to improve risk stratification and refine treatment algorithms in order to select the best individual treatment for arrhythmia suppression and prevention of sudden death in patients with ARVC.     

Arrhythmogene rechtsventrikuläre Kardiomyopathie

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disease and a major cause of sudden cardiac death and ventricular tachyarrhythmia in young, apparently healthy individuals and athletes. Patients affected by ARVC should be excluded from competitive sports and vigorous training. To provide optimal treatment, early diagnosis and risk stratification are mandatory and genetic counseling of families is recommended. Tailored treatment strategies aim at the prevention of ventricular tachyarrhythmia and sudden death as well as the preclusion of disease progression and symptomatic heart failure. Patients with a low risk of sudden death need either no specific treatment or can be treated with beta blockers or antiarrhythmic drugs, depending on the clinical manifestation of the arrhythmia. Catheter ablation in ARVC constitutes a symptom-oriented and palliative approach for frequently relapsing ventricular tachycardia refractory to antiarrhythmic medication. However, despite good acute results of catheter ablation, there is a high incidence of recurrence during long-term follow-up. In patients with ARVC at high risk of sudden death, implantation of an implantable cardioverter defibrillator (ICD) improves long-term survival by detection and termination of life-threatening ventricular arrhythmias. In the long term, however, the cumulative incidence of mainly lead-related complications of ICD therapy must be considered in the young population with ARVC, particularly when the indications are for primary prevention of sudden death or life-threatening arrhythmias. The proposed algorithm of therapeutic management in ARVC is under constant validation, development and refinement.     

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.     

Sudden cardiac death: Epidemiologic and financial worldwide perspective

The term sudden cardiac death (SCD) implies the sudden and unexpected loss of an active, productive member of the community. SCD is typically attributed to lethal ventricular arrhythmias; however, these arrhythmias are impossible to diagnose after the fact. Epidemiologic analyses, therefore, rely on inference of the cause of death. Estimates of the incidence of are SCD variable but it may be as high as 1 per 1,000 per year. The cost of SCD to society is incalculable. Current strategies for preventing SCD rely on risk assessment for cardiology patients and implantation of defibrillators (ICD) in high risk patients. Unfortunately, the absolute number of SCDs that occur in the general (relatively low-risk) population is large compared to the number of SCDs in the high risk population. Therefore, prevention of SCD in high risk populations is unlikely to prevent the majority of SCDs. Cost-effectiveness of ICD implantation for prevention of SCD has been studied; ICDs appear to meet U.S. and European criteria for cost-effectiveness if their benefit extends to at least 7–8 years. However, therapies considered cost-effective may nonetheless be too costly for most worldwide societies. Currently, investigators are focusing on refining risk stratification, partly in hopes of identifying patients for whom ICD implantation will not be useful.     

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）。     

Sudden Cardiac Death Unresponsive to Implantable Defibrillator Therapy: An Urgent Target for Clinicians,Industry and Government

A major expansion in utilization of implantable cardioverter-defibrillators (ICDs) is anticipated based on the results of randomized clinical trials (RCT) that demonstrate increased survival in a sizable population of patients with reduced left ventricular function. However, if RCT accurately reflect clinical practice, then a substantial proportion of patients will die suddenly despite ICD implantation. ICD-unresponsive sudden cardiac death (SCD) has been recognized since the initial ICD experience. Yet, despite 25 years of technical advances, the frequency of ICD-unresponsive SCD has not declined. Pooled analysis of RCT indicates a crude rate of ICD-unresponsive SCD of 5%. This may not cause alarm in an average practice, but it comprises about 30% of cardiac deaths. Meta-analyses of RCT show that ICD therapy is associated with a relative risk reduction of SCD of approximately 60%, far less than the greater than 90% efficacy that many expect. The suboptimal performance of ICD therapy accounts for the failure of some RCT to achieve statistically significant effects on survival. The number of patients with ICD-unresponsive SCD is highly correlated with the number of cardiac deaths among control patients as well as ICD recipients. Otherwise, no definite patterns have emerged that clearly distinguish this mode of demise from other modes of cardiac death. Retrospective post-hoc analyses have not revealed distinguishing characteristics of patients with ICD-unresponsive SCD with respect to clinical variables, pre-terminal symptoms or to the setting of the terminal event. Despite advanced storage capabilities of implanted devices, almost no information has become available from RCT regarding the terminal rhythm or the response of the ICD. These observations have implications for clinical management and research. Candidates for ICD implantation based on RCT should be accurately informed about the residual risk of SCD. Investigators seeking to identify populations likely to benefit from ICD therapy based on SCD incidence should recognize that a significant fraction may not respond to ICD therapy. Reducing the incidence of ICD-unresponsive SCD would substantially improve survival and cost-effectiveness related to ICD therapy. Close cooperation between clinicians, investigators and representatives of industry and government is urgently needed to develop strategies to identify patients prone to ICD-unresponsive SCD, to determine its mechanisms and to develop methods of prevention and treatment.     

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.     

Sudden death related cardiomyopathies - Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a form of inherited cardiomyopathy. Most individuals with HCM experience minimal symptoms throughout their lifetime. However, those with HCM are at risk of ventricular arrhythmias and sudden cardiac death (SCD), the most feared complication of HCM. Implantable cardioverter defibrillator (ICD) implantation has played a large role in transforming this disease from one with an ominous prognosis to one with mortality rates that are on par with the general public. Since the early 2000s, balance between SCD prevention and unnecessary ICD placement has been sought, this is reflected in the evolution of SCD risk stratification models for patients with HCM. This review discusses key concepts pertaining to HCM, with emphasis on prevention of SCD, and summarizes and compares the recommendations for ICD implantation in current guidelines.     

Risk factors for sudden cardiac death to determine high risk patients in specific patient populations that may benefit from a wearable defibrillator

BACKGROUND There is a high risk for sudden cardiac death(SCD) in certain patient groups that would not meet criteria for implantable cardioverter defibrillator(ICD) therapy.In conditions such as hypertrophic cardiomyopathy(HCM) there are clear risk scores that help define patients who are high risk for SCD and would benefit from ICD therapy. There are however many areas of uncertainty such as certain patients post myocardial infarction(MI). These patients are high risk for SCD but there is no clear tool for risk stratifying such patients.AIM To assess risk factors for sudden cardiac death in major cardiac disorders and to help select patients who might benefit from Wearable cardiac defibrillators(WCD).METHODS A literature search was performed looking for risk factors for SCD in patients post-MI, patients with left ventricular systolic dysfunction(LVSD), HCM, long QT syndrome(LQTS). There were 41 studies included and risk factors and the relative risks for SCD were compiled in table form.RESULTS We extracted data on relative risk for SCD of specific variables such as age,gender, ejection fraction. The greatest risk factors for SCD in post MI patients was the presence of diabetes [Hazard ratio(HR) 1.90-3.80], in patient with LVSD was ventricular tachycardia(Relative risk 3.50), in LQTS was a prolonged QTc(HR36.53) and in patients with HCM was LVH greater than 20 mm(HR 3.10). A proportion of patients currently not suitable for ICD might benefit from a WCDCONCLUSION There is a very high risk of SCD post MI, in patients with LVSD, HCM and LQTS even in those who do not meet criteria for ICD implantation. These patients may be candidates for a WCD. The development of more sensitive risk calculators to predict SCD is necessary in these patients to help guide treatment.     

The use of implantable cardioverter-defibrillators in patients at high risk of sudden cardiac death

We have reviewed literature on contemporary views on sudden cardiac death (SCD), detection of category of patients belonging to the group with high risk of SCD, and methods of SCD prevention. Randomized studies on assessment of efficacy of implantable cardioverter-defibrillators (ICD) for primary and secondary prevention of SCD have been reviewed in detail as well. We also present experience with clinical management of patients with ICD in the Main Military Clinical Hospital named after N.N.Burdenko. Primary implantations were carried out in 42 patients (5 women) aged 52.7+/-11.9 (19-80) years for secondary (40 patients) or primary (2 patients) SCD prevention. In most patients etiological factor of life threatening ventricular arrhythmias was ischemic heart disease and indications on myocardial infarction in anamnesis (28 patients). In remaining 14 patients we diagnosed right ventricular arrhythmogenic dysplasia (6 patients), dilated cardiomyopathy (3 patients), hypertrophic cardiomyopathy (2 patients), long QT syndrome (2 patients), and the Brugada syndrome (1 patient). During follow-up (from 2 to 48 months, mean 23.7+/-15.4 months) 2 patients died in 5 and 11 months after ICD implantation. In this period ICD discharges were registered in 27 patients (64%). Only in 2 of them (5%) at subsequent testing of the device the therapy was considered unjustified.     

Implantable cardioverter-defibrillators in children

BACKGROUND: Implantable cardioverter-defibrillators (ICD) have been increasingly used in adult patients for the prevention of sudden cardiac death (SCD). The usefulness and feasibility of ICD implantation in children have been less well established. AIM: To analyse indications, results and safety of ICD therapy in children. METHODS: ICDs were implanted in seven children, aged from 6 to 17 years. All patients underwent cardiological evaluation which included analysis of medical history, physical examination, chest X-ray, standard ECG, 24-hour Holter ECG monitoring and echocardiography. RESULTS: In five children devices were implanted due to aborted sudden death (ventricular fibrillation) whereas in the remaining two - as a primary prevention of SCD. Three children had hypertrophic cardiomyopathy, one - dilated cardiomyopathy, one - mitral valve prolapse and QT prolongation, one - congenital long QT syndrome and the remaining patient - idiopathic ventricular tachycardia. Single-chamber devices were implanted in six children, and dual-chamber system - in one patient. In all patients endocardial leads were implanted and ICD pocket was formed under the greater pectoral muscle. During follow-up ranging between four months to 5.4 years, four children developed ventricular fibrillation or ventricular tachycardia which were terminated by appropriate ICD discharges. CONCLUSIONS: 1. ICD implantation in children is effective in the prevention of SCD. 2. In our population, the most frequent indications for device implantation were life-threatening ventricular arrhythmias occurring in patients with cardiomyopathy. 3. Cardiac arrest due to ventricular fibrillation may occur in children without a history of aborted SCD. 4. ICD implantation in children is feasible and safe.     

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   

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.     

Decrease in amplitude of intracardiac ventricular electrogram and inappropriate therapy in patients with an implantable cardioverter defibrillator

Intracardiac electrograms are important for discrimination of tachyarrhythmia by implantable cardioverter defibrillators (ICD). A low R-wave can cause not only undersensing of ventricular tachyarrhythmia but also inappropriate discharges due to oversensing of unexpected signals because of its characteristic sensing algorithm. Therefore, this study aimed to investigate adverse events associated with R-wave amplitude. We included 115 consecutive patients followed-up over one year after implantation of a transvenous ICD system. The status of the ICD was checked every 3 months and intracardiac ventricular electrograms were analyzed. The decrease in R-wave amplitude was high in arrhythmogenic hypertrophy cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), and sarcoidosis. Low R-waves (< 5.0 mV) were observed in 13 patients at a follow-up of 15 +/- 16 months after implantation, and the mean R-wave was 3.0 +/- 0.8 mV. The frequency of low R-waves was high in ARVC (38%), sarcoidosis (33%), and dilated cardiomyopathy (17%). All of the dilated cardiomyopathy patients with low R-waves had severe left ventricular dysfunction. Inappropriate ICD therapy resulting from T-wave oversensing occurred in 7 patients and the R-wave was < 5.0 mV in 6 of the patients. The frequency of inappropriate therapy was high in patients with sarcoidosis. In 3 patients, inappropriate therapy caused ventricular tachyarrhythmia. In conclusion, decreases in R-wave amplitude occurred in some progressive cardiac disorders and caused inappropriate ICD discharges having arrhythmogenicity. Physicians should attempt to obtain a high R-wave amplitude during ICD implantation and careful follow-up is required, especially in patients with ARVC or sarcoidosis.     

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.     

The role of prophylactic implantable cardioverter defibrillators in heart failure: Recent trials usher in a new era of device therapy

Sudden cardiac death (SCD) manifested as ventricular fibrillation or sustained ventricular tachycardia has been a major focus of cardiovascular research for more than three decades. Although mortality in patients with heart failure (HF) caused by left ventricular systolic dysfunction has declined in recent years through effective pharmacotherapeutic strategies, SCD remains the major cause of death in symptomatic HF, with little improvement by drug therapy. Although it is clear that the implantable cardioverter defibrillator (ICD) is efficacious and should be used to prevent a recurrence of sustained ventricular arrhythmia (secondary prevention) in most patients, the guidelines for prophylactic use of ICDs (primary prevention) are less well defined. The results of recent clinical trials examining the efficacy of prophylactic ICD therapy in HF patients have clarified the role of ICD treatment in this population. This article reviews these trials and summarizes our current approach to the prevention of SCD in HF.     

Arrhythmogenic Right Ventricular Cardiomyopathy Antiarrhythmic Drugs, Catheter Ablation, or ICD?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death and ventricular tachyarrhythmias in young, apparently healthy individuals and athletes. Myocardial atrophy with subsequent fibrofatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness which are prerequisites for reentrant ventricular tachyarrhythmias.Patients affected with ARVC should be excluded from competitive sports and vigorous training. To provide optimal treatment, a detailed diagnostic evaluation and risk stratification are mandatory. Tailored treatment strategies aim at the suppression or effective termination of recurrent ventricular tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy, catheter ablation, or implantation of a cardioverter defibrillator (ICD).