Prevention Of Sudden Cardiac Death In Patients Research Articles

Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies.

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age- and sex-matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better-informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in-depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non-dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarizes established and emerging risk factors for life-threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence-based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification.

The role of entirely subcutaneous ICD™ systems in patients with dilated cardiomyopathy

BackgroundThe subcutaneous implantable-cardioverter defibrillator (S-ICD™, Boston Scientific, Natick, MA, USA) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICD™ use, long-term data are still limited, especially in subgroups. Dilated cardiomyopathy (DCM) is a common reason for the implantation of an ICD. However, there are no sufficient data on the performance of the S-ICD™ in this patient cohort. Materials and methodsAll S-ICD™ patients with DCM as the main indication for ICD implantation (n=47 patients) in our large-scaled single-center S-ICD™ registry (n=294 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 22.9±18.5 months. ResultsA total of 47 patients with DCM as the underlying structural heart disease received an S-ICD™ in our institution. Mean left ventricular ejection fraction was 37±12% and a 28% had a history of ventricular tachyarrhythmia. During follow-up eight ventricular tachyarrhythmias were adequately terminated in three patients. In four patients, oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector. There was no need for a change to a cardiac resynchronization (CRT) system while one system was changed to a VVI-ICD due to S-ICD™ wound infection. ConclusionThe S-ICD™ seems to be a valuable option for the prevention of SCD in patients with DCM and no indication for CRT. As clinically relevant ventricular arrhythmias consisted of ventricular fibrillation or fast ventricular tachycardia in all patients in our cohort, no change to transvenous ICDs for anti-tachycardia pacing delivery was necessary.

Rare but lethal short QT syndrome: most recent understanding of the disease

Short QT syndrome (SQTS) is a rare genetic channelopathy that affects the repolarization of cardiac cells and is associated with cardiac arrhythmia and sudden cardiac death (SCD). “Abbreviated repolarization” is the hallmark of the disease, which is secondary to genetic defects; mutations in several genes that encode different cardiac ion channels have been identified in individuals with the disease. Presentations of the disease include syncope, atrial or ventricular arrhythmia and SCD. SQTS is diagnosed with a corrected-QT (QTc) interval of <340 milliseconds (ms) or a QTc of 340-360 ms and either personal or family history of SCD, family history of SQTS or an identified genetic mutation. Implantable cardioverter-defibrillator (ICD) is the main treatment used in the secondary prevention of SCD in patients with the disease who have experienced previous major arrhythmic events. Pharmacological treatment with quinidine is used as an adjuvant therapy to ICD in the setting of recurrent shocks or as an alternative treatment when ICD is not feasible. The goal of this review article is to describe this rare and under-studied condition, highlight steps to diagnosis and describe treatment modalities, particularly in South America where there is a lack of studies and understanding of this disease.

The entirely subcutaneous ICDTM system in patients with congenital heart disease: experience from a large single-centre analysis.

The subcutaneous implantable cardioverter-defibrillator (S-ICDTM) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICDTM use, long-term data are still limited, especially in subgroups such as adult patients with congenital heart diseases. This cohort is of high interest because of the difficult anatomic conditions in these patients. All S-ICDTM patients with an underlying congenital heart disease (CHD) resulting in an indication for ICD implantation (n = 20 patients) in our large-scaled single-centre S-ICDTM registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 36 months. Primary prevention of SCD was the indication for implantation of an S-ICDTM in six patients (30%). Of all 20 patients with an overall mean age of 40.5 ± 11.5 years, 12 were male (60%). The mean left ventricular ejection fraction was 46.5 ± 11.3%. Nine episodes of ventricular tachycardia (two monomorphic and seven polymorphic) were adequately terminated in three patients (15%). In two patients, T-Wave-Oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector or activation of the SMART PASSTM filter. There were no S-ICDTM system-related infections. In one patient, surgical revision was necessary due to a persistent haematoma. The S-ICDTM seems to be a valuable option for the prevention of SCD in patients with various CHDs and complex anatomical anomalies. The S-ICDTM is safe and works effectively, also in these complex patients. Inadequate shock delivery was rare and could be managed by reprogramming.

Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

Implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is controversial in view of the recent DANISH trial which suggested no benefit with ICD for primary prevention in patients with non-ischemic cardiomyopathy (NICMP). We conducted a meta-analysis of randomized control trials studying the role of ICD in primary prevention of SCD in patients with NICMP. Only six studies were identified after the application of inclusion/exclusion criteria. Pooling of these randomized trials showed a statistically significant benefit of using ICDs in patients with NICMP [OR 0.76 (0.64 - 0.91), I2 = 0%]. Sensitivity analysis did not show a statistically significant mortality benefit of ICD in NICMP in trials which had adequate beta blocker, ACE/ARB and aldosterone receptor blocker (ALD-RB) use [OR 0.70 (0.41, 1.19), I2 = 70%]. The DANISH trial's failure to show mortality benefit may be due to the significant number of patients who had CRT. Our meta-analysis studied the independent effect of ICDs and showed them to be associated with net mortality benefits in patients who are not on optimal guideline directed medical therapy; especially the patients not on ALD-RB.

[Sudden cardiac death : Epidemiology, pathophysiology and risk stratification].

Sudden cardiac death (SCD) remains amajor public health burden despite revolutionary progress in the last three decades in the treatment of ventricular tachyarrhythmia with the use of implantable cardioverter defibrillator (ICD) therapy. Survivors of sudden cardiac arrest are at high risk for recurrent tachyarrhythmia events. Early recognition of low left ventricular ejection fractions (≤35%) as astrong predictor of mortality and the causal association between ventricular tachyarrhythmia and SCD has led to asignificant development of not only pharmacological antiarrhythmic therapy but also device-based prevention of SCD. The ICD therapy is nowadays routinely used for primary prevention of SCD in patients with significant structural cardiomyopathy and primary electrical arrhythmia syndromes, which are associated with high a risk and secondary prevention in survivors of sudden cardiac arrest. Additionally, effective approaches exist to significantly reduce the recurrence rate of ventricular tachyarrhythmia of various origins by complex electrophysiological endocardial and epicardial catheter ablation procedures.

The Wearable Cardioverter Defibrillator in Nonischemic Cardiomyopathy: A US National Database Analysis

BackgroundThe wearable cardioverter defibrillator (WCD) is often used in patients at risk of sudden cardiac death (SCD) who are not yet candidates for an implantable cardioverter defibrillator (ICD). Newly diagnosed cardiomyopathy may be reversible, and a WCD may protect patients during the initial period of risk. We evaluate the benefit and compliance of the WCD in patients with nonischemic cardiomyopathy (NICM). MethodsWe reviewed a national database of patients with NICM who used WCDs and who self-reported a history of excess alcohol use, although other causes of cardiomyopathy could not be excluded. The database contained demographic data, initial ejection fraction (EF), reason for WCD prescription, compliance and use data, any detected arrhythmias, therapies, and reason for discontinuing WCD. Statistical analyses were performed using SAS, version 9.3 (SAS Institute, Cary, NC). ResultsOf the 127 patients, 88% were men with a mean age of 52.6 ± 11.0 years. The mean initial EF was 19.9% ± 7.4%. Patients wore the WCD for a median of 51 days and a median daily use of 18.0 hours per day. The most common reasons for discontinuing the WCD were improvement in EF (33%) or ICD implantation (23.6%). Seven patients (5.5%) had 9 sustained ventricular arrhythmia events, which were successfully treated with 100% conversion. There were 11 deaths (8.6%) during 100 days of follow-up. No deaths resulted from WCD shock failure or undersensing. ConclusionsNICM may have a significant risk of ventricular arrhythmias and death in the first few months. The WCD delivered appropriate therapy in 5.5% of patients. This study suggests that a WCD may be effective temporary prophylaxis for prevention of SCD in patients with newly diagnosed NICM.

The Wearable Cardioverter Defibrillator: an Early Single Centre Australian Experience. Some Pitfalls and Caveats for Use

Wearable Cardioverter Defibrillators (WCD) have been effectively used for more than a decade in North America and Europe for prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. This device has only recently been available in Australia. At Westmead hospital, WCD has been used since 2013 as a bridging therapy to an implantable cardioverter defibrillator (ICD) for those at high risk, but are temporarily not suitable for an implantable device. Indications for use were explanted infected ICD, dilated cardiomyopathy, post partum cardiomyopathy, valvular heart disease and myocarditis. The default device settings were: ventricular tachycardia (VT) and ventricular fibrillation (VF) threshold of 150 bpm and 200 bpm respectively and response times were 60 secs for VT and 25 secs for VF. WCD was used in eight patients. Duration of use ranged from five to 180 days with median of 77 days. Daily usage averaged 23.4±0.6hours. All except one were compliant with the device and none of our patients received shock or died during device usage. Four of the eight patients received ICD, two declined ICD, one was judged to no longer require ICD and one remains under assessment. WCD is easy to use, well tolerated and is effective for SCD prevention in patients who are temporarily not suitable for ICD. However patients need to be actively followed-up to reduce the duration of WCD usage and thereby be cost effective.

Clinical Management and Prevention of Sudden Cardiac Death

Despite the revolutionary advancements in the past 3 decades in the treatment of ventricular tachyarrhythmias with device-based therapy, sudden cardiac death (SCD) remains an enormous public health burden. Survivors of SCD are generally at high risk for recurrent events. The clinical management of such patients requires a multidisciplinary approach from postresuscitative care to a thorough cardiovascular investigation in an attempt to identify the underlying substrate, with potential to eliminate or modify the triggers through catheter ablation and ultimately an implantable cardioverter-defibrillator (ICD) for prompt treatment of recurrences in those at risk. Early recognition of low left ventricular ejection fraction as a strong predictor of death and association of ventricular arrhythmias with sudden death led to significant investigation with antiarrhythmic drugs. The lack of efficacy and the proarrhythmic effects of drugs catalyzed the development and investigation of the ICD through several major clinical trials that proved the efficacy of ICD as a bedrock tool to detect and promptly treat life-threatening arrhythmias. The ICD therapy is routinely used for primary prevention of SCD in patients with cardiomyopathy and high risk inherited arrhythmic conditions and secondary prevention in survivors of sudden cardiac arrest. This compendium will review the clinical management of those surviving SCD and discuss landmark studies of antiarrhythmic drugs, ICD, and cardiac resynchronization therapy in the primary and secondary prevention of SCD.

Application of ICD guidelines and indications in a community-based academic hospital: a case series-based discussion

BackgroundImplantable cardioverter defibrillators (ICDs) are indeed beneficial in selected patients as evidenced by multiple large randomized controlled trials (RCTs) since 1980. A systematic method for stratification of patients and hospital-wide criteria/guidelines to ascertain appropriate device implantation became necessary.MethodsMajor ICD/CRT (cardiac resynchronization therapy) clinical studies and relevant guidelines were reviewed, and an institution-wide inclusion and exclusion criteria for ICD/CRT was formulated. A retrospective analysis of selected cases was performed to discuss the criteria and special clinical situations.ResultsWe have translated the evolving ICD/CRT studies into a standard of care at our hospital by formulating a standard, practical, and update-to-date ICD inclusion and exclusion criteria. Thirteen cases were selected to represent major indications and contraindications of ICDs in our practice. These cases cover indications of ICD for secondary prevention of sudden cardiac death (SCD), primary prevention of SCD in patients with CHF resulted from either ischemic or non-ischemic cardiomyopathy, as well as for infiltrative cardiomyopathy and inherited conditions. We discussed the application of CRT in patients with CHF associated with prolonged QRS duration. We then covered the potential benefits of ICD with/without CRT in certain special populations of patients that have not been adequately evaluated by currently available RCTs; these include alcoholic, elderly, female, and ESRD/HD patients. Finally, we addressed risks, complications and contraindications of ICD, as well as application of an external wearable defibrillator in AMI, or status post-CABG patient during the mandatory waiting period for an ICD.ConclusionsEstablishment of the ICD/CRT criteria represents a practical translation of emerging CRTs and helps to standardize patient care in our hospital. It also improves cost-effectiveness as well as appropriate utilization of institute and device resources.

Tools for risk stratification of sudden cardiac death: A review of the literature in different patient populations

While various modalities to determine risk of sudden cardiac death (SCD) have been reported in clinical studies, currently reduced left ventricular ejection fraction remains the cornerstone of SCD risk stratification. However, the absolute burden of SCD is greatest amongst populations without known cardiac disease. In this review, we summarize the evidence behind current guidelines for implantable cardioverter defibrillator (ICD) use for the prevention of SCD in patients with ischemic heart disease (IHD). We also evaluate the evidence for risk stratification tools beyond clinical guidelines in the general population, patients with IHD, and patients with other known or suspected medical conditions.

Protection from outpatient sudden cardiac death following ICD removal using a wearable cardioverter defibrillator.

An implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death (SCD). Once an ICD is removed and reimplantation is not feasible, a wearable cardioverter defibrillator (WCD) may be an alternative option. We determined the effectiveness of WCD for SCD prevention in patients who were discharged after ICD removal. A retrospective study was conducted on all WCD (LifeVest, ZOLL, Pittsburgh, PA, USA) patients who underwent ICD removal due to cardiac device infections (CDIs) at two referral centers between January 1, 2005 and December 31, 2009. Clinical characteristics, device information, and WCD data were analyzed. Sudden cardiac arrest was defined as all sustained ventricular tachycardia (VT) and ventricular fibrillation occurring within a single 24-hour period. Ninety-seven patients (mean age 62.8 ± 13.3, male 80.4%) were included in the study. The median duration of antibiotic use was 14.7 days (interquartile range [IQR] 10-30). The median daily WCD use was 20 hours/day and the median length of use was 21 days (IQR 5-47). A total of three patients were shocked by WCD. Two patients had four episodes of sustained VT, successfully terminated by the WCD. A third patient experienced two inappropriate treatments due to oversensitivity of the signal artifact. Three patients experienced sudden death outside the hospital while not wearing the device. Five patients died while hospitalized. WCD can prevent SCD, until ICD reimplantation is feasible in patients who underwent device removals for CDI. However, patient compliance is essential for the effective use of this device.

Current Evidence Base for Use of the Implantable Cardioverter–Defibrillator

Almost 4 decades after its conception the implantable cardioverter–defibrillator (ICD) has emerged as a widely accepted treatment modality for the prevention of sudden cardiac death (SCD). The indications for ICD therapy have rapidly expanded over the past 10 years, and, today, >100 000 ICDs are implanted annually in the United States. More recently, however, some have raised words of caution as to the potential overestimation of ICD-associated benefits and hazards in individual patients.1,2 Therefore, this review summarizes the current scientific basis for ICD indications, puts it in context with recent guidelines, and discusses areas where additional trial evidence is needed to clarify pending issues regarding the optimal use of device therapy. The term secondary prevention refers to the prevention of SCD in patients who have survived previous cardiac arrest or an episode of sustained ventricular tachycardia (VT). The term primary prevention of SCD describes patient populations known to be at high risk for cardiac arrest because of preexisting cardiovascular disease but who have not yet experienced sustained VT or ventricular fibrillation (VF).3 ### Secondary Prevention Trials The secondary prevention strategy that emerged from observations indicating a high recurrence rate of VT or VF in survivors of cardiac arrest4,5 was the first to be tested in randomized clinical trials (Table 1). There are 3 secondary prevention ICD trials, the Antiarrhythmics Versus Implantable Defibrillator (AVID) trial, the Canadian Implantable Defibrillator (CIDS) trial, and the Cardiac Arrest Study Hamburg (CASH) trial, all initiated between the late 1980s and early 1990s.6–8 The AVID trial was the first to report its results and showed a statistically significant survival benefit over antiarrhythmic drugs (mostly amiodarone), with an absolute risk reduction of 7% over 2 years.6 After publication of AVID, the CIDS trial was prematurely stopped owing to the similarities between …

Sudden cardiac death after repair of anomalous origin of left coronary artery from right sinus of Valsalva with an interarterial course : Case report and review of the literature.

Anomalous aortic origin of the coronary artery from the opposite sinus with interarterial course (AAOCA) is a rare condition with a high risk of sudden cardiac death (SCD) during or after strenuous exertion. SCD after repair of this anomaly is extremely rare. Here we present a 15-year-old athlete who collapsed on the basketball court in whom an anomalous origin of the left coronary artery from the right sinus of Valsalva with interarterial course (ALCA) was diagnosed. In spite of extensive pre-sport participation testing, SCD occurred shortly after surgical correction. We reviewed the literature to establish an evidence-based recommendation to aid physicians in conducting the optimal pre-sport participation management for the prevention of SCD in patients with a surgically corrected AAOCA/ALCA, especially for those who participate in strenuous exercise. Review of the literature (60 articles with 325 patients) reveals that post-surgical, pre-sport participation testing varies greatly but that mortality after surgical repair is extremely low (1.5%). In conclusion, SCD can still rarely occur after repair of AAOCA despite extensive pre-sport participation testing. This should raise awareness among physicians treating these patients and raises the question whether or not return-to-play guidelines need to be revised.

Effects of Omega-3 Fatty Acid for Sudden Cardiac Death Prevention in Patients with Cardiovascular Disease: A Contemporary Meta-Analysis of Randomized, Controlled Trials

Experimental and epidemiological studies suggest that omega-3 fatty acids have an antiarrhythmic effect. However, evidence from randomized controlled trials (RCTs) for prevention of sudden cardiac death (SCD) remains controversial. This study sought to evaluate the efficacy of omega-3 fatty acids for secondary prevention of SCD in patients with cardiovascular disease (CVD) in the era of guidelines-based therapy. We conducted a PubMed/EMBASE/CENTRAL search for RCTs evaluating omega-3 fatty acids for CVD secondary prevention with at least 6 months follow-up and with data on SCD. Primary outcome was SCD. Secondary outcomes were cardiovascular mortality and all-cause mortality. Ten randomized controlled trials were identified evaluating a total of 33,429 patients with CVD. In patients with guidelines-adjusted therapy, omega-3 fatty acids did not reduce the risk ratio (RR) of SCD (RR:0.96; 95% CI: 0.84-1.10). In patients with non- guidelines-adjusted therapy, omega-3 fatty acids reduced the RR of SCD (RR: 0.64; 95% CI: 0.51-0.80). Overall, RR for cardiac death and all-cause mortality were 0.81 (95% CI: 0.69-0.95) and 0.89 (95% CI: 0.79-1.01), respectively. In the era of guidelines-adjusted treatment for CVD secondary prevention, omega-3 fatty acids do not appear to reduce SCD.

Implantable Cardioverter‐Defibrillator in Patients With Hypertrophic Cardiomyopathy: Efficacy and Complications of the Therapy in Long‐Term Follow‐up

Although implantable cardioverter-defibrillators (ICDs) are used in sudden cardiac death (SCD) prevention in high-risk patients with hypertrophic cardiomyopathy (HCM), long-term results as well as precise risk stratification are discussed in a limited number of reports. The aim of the study was to assess the incidence of ICD intervention in HCM patients with relation to clinical risk profile. We studied 104 consecutive patients with HCM implanted in a single center. The mean age of study population was 35.6 (SD, 16.2) years with the average follow-up of 4.6 (SD, 2.6) years. ICD was implanted for secondary (n = 26) and primary (n = 78) prevention of SCD. In the secondary prevention group, 14 patients (53.8%) experienced at least 1 appropriate device intervention (7.9%/year). In the primary prevention (PP) group appropriate ICD discharges occurred in 13 patients (16.7%) and intervention rate was 4.0%/year. Nonsustained VT was the only predictive risk factor (RF) for an appropriate ICD intervention in the PP (positive predictive value 22%, negative predictive value 96%). No significant difference was observed in the incidence of appropriate ICD discharges between PP patients with 1, 2, or more RF. Complications of the treatment included: inappropriate shocks (33.7%), lead dysfunction (12.5%), and infections: 4.8% of patients. Four patients died during follow-up. ICD therapy is effective in SCD prevention in patients with HCM, although the complication rate is significant. Nonsustained ventricular tachycardia seems to be the most predictive RF for appropriate device discharges. Number of RF did not impact the incidence of appropriate ICD interventions.

ICD therapy in women: Are men from Mars and women from Venus?

Heart failure affects approximately 5.8 million people in the United States, with women composing nearly half that population. 1 Lloyd-Jones D. Adams R.J. Brown T.M. et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010; 121: e46-e215 Crossref PubMed Scopus (1385) Google Scholar The annual incidence of heart failure is approximately 670,000 in patients ages 45 years and older, with men and women affected in equal numbers. 1 Lloyd-Jones D. Adams R.J. Brown T.M. et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010; 121: e46-e215 Crossref PubMed Scopus (1385) Google Scholar Treatment of heart failure patients with severe systolic dysfunction includes optimization of medical therapy in addition to primary prevention of sudden cardiac death (SCD) with implantation of an implantable cardioverter-defibrillator (ICD). 2 Hunt S.A. Abraham W.T. Chin M.H. et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009; 119: e391-e479 Crossref PubMed Scopus (1400) Google Scholar , 3 Hunt S.A. Abraham W.T. Chin M.H. et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005; 112: e154-e235 Crossref PubMed Google Scholar This approach to the primary prevention of SCD in patients with heart failure is the result of multiple clinical trials that have evaluated the efficacy of ICDs in this population. 4 Moss A.J. Zareba W. Hall W.J. et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346: 877-883 Crossref PubMed Scopus (5576) Google Scholar , 5 Bardy G.H. Lee K.L. Mark D.B. et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005; 352: 225-237 Crossref PubMed Scopus (5257) Google Scholar The integration of these results into practice guidelines has led to a significant increase in the rate of ICD implantation in the United States. 6 Hammill S.C. Kremers M.S. Kadish A.H. et al. Review of the ICD Registry's third year, expansion to include lead data and pediatric ICD procedures, and role for measuring performance. Heart Rhythm. 2009; 6: 1397-1401 Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar Gender differences in clinical outcome and primary prevention defibrillator benefit in patients with severe left ventricular dysfunction: A systematic review and meta-analysisHeart RhythmVol. 7Issue 7PreviewWomen are underrepresented in primary prevention implantable cardioverter-defibrillator (ICD) trials, and data on the benefit of ICD therapy in this subgroup are controversial. Full-Text PDF

Implantable Cardioverter–Defibrillators for Primary Prevention of Sudden Cardiac Death

Sudden cardiac death (SCD) remains a major cause of death in the industrialised world. Implantable cardioverter–defibrillators (ICDs) have been shown to be an effective therapy option for the primary prevention of SCD in patients at high risk of SCD. This review will discuss adequate risk stratification in various disease states, such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathies (dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), channelopathies (Brugada syndrome, long- QT syndrome, short-QT syndrome, catecholaminergic polymorphic ventricular tachycardia) and congenital heart diseases, to identify patients at high risk of SCD and selection criteria for ICD therapy. The most important clinical primary prevention trials will be highlighted. Finally, complications of device therapy and quality of life issues will be addressed.

Noninvasive Arrhythmia Risk Assessment in Guiding Pharmacologic Therapy for Prevention of Sudden Cardiac Death: Where Do We Stand? Where Do We Go?

Despite reductions in age-adjusted death rates in patients with cardiovascular disease over the past 20 years, approximately 325,000 deaths still occur suddenly and unexpectedly each year.1 In 20% to 30% of cases, sudden cardiac death (SCD), commonly defined as death within 1 hour after onset of symptoms, occurs without warning. It is generally assumed that this mode of demise is attributable mainly to ventricular tachycardia and fibrillation, although this event can be difficult to document, an inherent limitation in SCD studies. Nevertheless, the scope of this public health problem and the need for progress provide a compelling rationale for development of noninvasive markers to stratify risk for life-threatening arrhythmias and to guide preventive pharmacologic therapy. The present two-part series addresses the advances in noninvasive risk stratification and the evolution of pharmacologic therapy for prevention of SCD, which has progressed beyond targeting ion channels to include myocardial substrate changes, particularly those related to arrhythmogenic postmyocardial infarction remodeling. The first group of reviews focuses on basic mechanisms, conventional antiarrhythmic and nonantiarrhythmic agents for SCD prevention, and the utility of T-wave alternans (TWA) in guiding pharmacologic therapy. Rosen and Janse place the development of antiarrhythmic agents within the framework of the “vulnerable parameter,” first advanced in the Sicilian Gambit nearly two decades ago.2 The Gambit conference assembled an interdisciplinary group of leading scientists and clinicians in the field of antiarrhythmic drug therapy to stimulate the development and application of agents based on in-depth understanding of cellular and ionic mechanisms and molecular therapeutic targets. Fundamentally, a “vulnerable parameter” reflects an electrophysiological property, phenomenon, or ion channel that is within the causal pathway of arrhythmogenesis and can be altered by pharmacologic therapy to decrease the occurrence of arrhythmia. By definition, a noninvasive therapeutic marker encompasses one or more “vulnerable parameters” or arrhythmia mechanism targets. Guided by these concepts, Rosen and Janse review the history of antiarrhythmic drug development, basic mechanisms, and the ensuing major clinical trials, including Cardiac Arrhythmia Pilot Study (CAPS), Cardiac Arrhythmia Suppression Trial (CAST), and Survival With ORal D-Sotalol (SWORD). Important insights are provided into disappointing findings, particularly those from the CAST trial, along with lessons learned to guide future drug development. The authors also discuss the need for research to expand and modify the library of vulnerable parameters and the relevance of newer markers in this context. The need to go beyond ion channels to include consideration of substrate remodeling in association with myocardial infarction and cardiomyopathic heart disease is also underscored. Overall, their encompassing view of the complexities associated with arrhythmogenesis provides a valuable blueprint for future investigation. Das and Zipes address the clinically challenging problem of antiarrhythmic therapy for prevention of lethal ventricular tachyarrhythmias.3 They make the important points that although implantable cardioverter-defibrillator (ICD) discharge is the primary therapy for reducing SCD mortality, device implantation is expensive and is associated with mortality from proarrhythmia and mechanical malfunction. Importantly, ICDs serve a rescue function rather than providing prophylaxis. Their comprehensive review provides a state-of-the-art discussion of contemporary agents that act on adrenergic receptors and major ion channels as well as newer agents with nontraditional modes of action. The authors emphasize the promise of “nonantiarrhythmic” agents, including drugs that act on the renin-angiotensin-aldosterone system, fish oil, and statins. The latter can reduce the occurrence of ventricular tachycardia and fibrillation in patients with coronary artery disease or congestive heart failure. An additional important point noted is that a number of “traditional” antiarrhythmic agents carry risk for proarrhythmia and that “nonantiarrhythmic” agents are generally well tolerated and devoid of proarrhythmic actions. Further exploration of this newer mode of action appears highly worthwhile, especially with agents that improve left ventricular remodeling, which is increasingly recognized as an important factor in arrhythmogenesis. In the last review in the first part of the series, the utility of TWA, a beat-to-beat alternation in morphology and amplitude of the ST segment or T wave, as a noninvasive marker with potential to guide antiarrhythmic therapy is discussed by Verrier and Nieminen.4 The rationale for TWA is reviewed and the case is developed that this phenomenon, which has long been reported in association with life-threatening arrhythmias in patients with diverse conditions including ischemic heart disease, heart failure, and channelopathies, may serve as an index of risk for lethal ventricular tachyarrhythmias. The authors review the evidence that newer quantitative techniques to detect microvolt TWA, studied in more than 12,000 patients, support the predictivity of TWA testing for cardiovascular mortality and SCD not only during exercise testing, but more recently during ambulatory electrocardiogram (ECG) monitoring. Although the focus for TWA testing has been in guiding ICD implantation, a growing literature supports the potential utility of this tool to guide pharmacologic therapy. The clinical and basic research evidence supporting TWA as a therapeutic marker of antiarrhythmic and proarrhythmic effects is reviewed for the major drug classes. In each case, the direction of changes in TWA magnitude is consistent with the anti- or proarrhythmic effects of agents studied. Information is also provided that TWA may be helpful in detecting the beneficial effects of nonantiarrhythmic agents such as angiotensin II receptor blockade, presumably through an indirect action on myocardial remodeling. The authors conclude that quantitative analysis of TWA has considerable potential for guiding pharmacologic therapy and that this should be a topic of intensive investigation. The second part of the series focuses on the new marker of autonomic reflexes, heart rate turbulence (HRT); on left ventricular ejection fraction (LVEF), a mainstay for arrhythmia risk stratification; and on the QT interval as an indicator of repolarization abnormalities in newborns. Bauer, Zürn, and Schmidt discuss the use of HRT, an indicator of baroreceptor-mediated short-term oscillations in cardiac cycle length that follow spontaneous ventricular premature complexes.5 HRT is closely related to baroreceptor gain, provides a measure of the interplay between sympathetic and parasympathetic nerve activity, and can be monitored from standard ECG recordings. This parameter has been shown in sizeable studies to be a strong independent predictor of cardiovascular mortality in postmyocardial infarction patients and patients with heart failure. HRT appears not only to be correlated with patients' clinical status but also to exhibit a pattern of recovery when heart failure treatment, including beta-blockade, angiotensin-converting enzyme inhibition, or cardiac resynchronization therapy, is effective. Thus, there is considerable evidence that HRT may be useful as a treatment target to guide pharmacologic therapy. The pivotal topic of heart failure as a marker of risk for SCD is addressed by Buxton and colleagues.6 This parameter has received considerable attention and is currently applied in guiding ICD therapy for primary prevention of SCD in patients with coronary artery disease and/or nonischemic dilated cardiomyopathy. The MADIT II criterion of less than 30% LVEF in postmyocardial patients is extensively used.7 Buxton and colleagues point out that although low LVEF identifies patients with relatively increased risk for SCD, a number of factors limit the use of this parameter as a primary indicator for ICD implantation. A major point is the parameter's lack of sensitivity and specificity. Most patients who die suddenly have LVEF above the criterion level, and 17 of 18 individuals who receive ICD implants guided by LVEF do not experience device therapy. The authors suggest that shortcomings in predictivity relate to fact that LVEF is a measure of mechanical function and may be only indirectly related to mechanisms responsible for ventricular tachyarrhythmias. The role of LVEF in guiding pharmacologic therapy has not been adequately explored. The authors conclude that whereas this index is likely to remain a mainstay in sudden death risk stratification, there is potential value in combining it with other indicators, including measures of autonomic function and abnormal depolarization and repolarization, to encompass the potential influences of diverse arrhythmogenic factors and of specific mechanisms associated with underlying disease substrate and with progression in disease state. The challenging problem of identifying newborns at risk for arrhythmic death is addressed by Schwartz and Stramba-Badiale.8 The authors draw attention to the pressing need to identify abnormalities in ventricular repolarization that can lead to death in infants with the long QT syndrome. They assembled an impressive database of ECG recordings from 44,000 infants and analyzed QT interval distribution during the first month of life. Their work supports the rationale for widespread screening of ECGs to allow early detection of infants affected by long QT syndrome. This information also provides means for identification of the 51% of family members who may be silent carriers of the potentially lethal mutation. The authors discuss the potential effective therapies that can benefit from the early warning based on ECG monitoring. In summary, significant advances have been made both in noninvasive risk stratification and in pharmacologic therapies for prevention of SCD. It is likely that a number of the markers discussed may be combined to improve prognostic capacity. An important aspect of the evolving work is the recognition that noninvasive risk markers may provide insights into underlying mechanisms of arrhythmogenesis and thereby serve as “vulnerable parameters” or therapeutic targets for rational selection of prophylactic agents. The approach to antiarrhythmic therapy has also advanced in an innovative fashion. It appears that protecting the myocardium may involve not only addressing arrhythmogenic currents associated with disease, but also targeting myocardial substrate changes as a result of remodeling from myocardial infarction, heart failure, cardiomyopathy, and other conditions. As prospective trials are developed, there is also a treasure trove of archival ambulatory ECG trial data on both antiarrhythmic and nonantiarrhythmic agents in which a favorable outcome in terms of SCD has been documented and therefore provides a basis for evaluation of individual parameters and hypothesis testing. Accordingly, we are at an exciting frontier, poised to progress “beyond QT” and “beyond traditional ion channels” to improve diagnosis and pharmacologic therapy.9

Should Catheter Ablation be the Preferred Therapy for Reducing ICD Shocks?

In 1980, Mirowski et al1 implanted the first implantable cardioverter-defibrillator (ICD) in a young female with recurrent ventricular fibrillation and provided an innovative approach to aborted sudden cardiac death (SCD). Although the ICD was considered a treatment of last resort during that incipient stage, subsequent years have witnessed prolific expansion of indications for ICD implantation.2 Several large-scale clinical trials have demonstrated its efficacy for both primary and secondary prevention of SCD in patients with ischemic and nonischemic cardiomyopathy.3,4 ICD therapy in such high-risk patients has been shown to improve survival compared with conventional antiarrhythmic drug therapy alone.3,4 The number of ICD implantations has increased significantly in the last decade, with a concurrent decrease in the use of stand-alone antiarrhythmic drugs for ventricular indications.5–7 Current ICDs have sophisticated programming capabilities, atrial and bipolar leads, and are able to deliver antitachycardia pacing algorithms (ATP) in addition to defibrillating shocks. Response by Kuck on p 705 Typically, patients who receive ICDs are at high risk for recurrent arrhythmia; hence, most patients receive 1 or more ICD therapies for spontaneous arrhythmias after implantation.3 Despite the technological evolution of ICD systems, more than 20% of shocks are due to supraventricular arrhythmia and hence are inappropriate.8–10 The ICD uses ATP or defibrillating shocks to terminate episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF). Although the ICD aborts VT/VF, many patients continue to have symptoms such as dizziness, palpitations, nervousness, flushing, or syncope before receiving an ICD shock.11 When the shock is finally delivered, it is physically and emotionally painful and so noxious that 23% of patients dread shocks and 5% of patients prefer to do without an ICD and “take their chances.”12 A significant prevalence of sadness, depression, and even anxiety disorders have been reported after …