Primary Prophylactic Implantable Cardioverter Defibrillator Research Articles

Implementation of guidelines for implantable cardioverter-defibrillator therapy in clinical practice: Which patients do benefit?

PurposeBased on multiple large clinical trials conducted over the last decades guidelines for implantable cardioverter-defibrillator (ICD) implantations have been evolving. The increase in primary prophylactic ICD implantations challenges us to be critical towards the indications in certain patient populations.MethodsWe retrospectively collected patient characteristics and rates of appropriate and inappropriate ICD therapy, appropriate and inappropriate ICD shock and mortality of all patients who received an ICD in the University Medical Center Utrecht (UMCU) over the years 2006–2011.ResultsA total of 1075 patients were included in this analysis (74 % male, mean age 61 ± 13 years, left ventricular ejection fraction 30 ± 13 %); 61 % had a primary indication and 58 % had ischaemic heart disease. During a mean follow-up period of 31 ± 17 months, 227 of the patients (21 %) received appropriate ICD therapy (149 (14 %) patients received an appropriate ICD shock). Females, patients with a primary prophylactic indication and patients with non-ischaemic heart disease experienced significantly less ICD therapy. Only a few patients (54, 5 %) received inappropriate ICD therapy; 33 (3 %) patients received an inappropriate ICD shock. Fifty-five patients died within one year after ICD implantation and were therefore, in retrospect, not eligible for ICD implantation.ConclusionOur study confirms the benefit of ICD implantation in clinical practice. Nevertheless, certain patients experience less benefit than others. A more patient-tailored risk stratification based on electrophysiological parameters would be lucrative to improve clinical benefit and cost-effectiveness.

Clinical relevance of slow ventricular tachycardia in heart failure patients with primary prophylactic implantable cardioverter defibrillator indication

Implantable cardioverter defibrillators (ICDs) have shown to reduce all-cause mortality in heart failure patients. In SCD-HeFT study, ICDs were programmed with a detection zone of ≥ 187 b.p.m. Thus, the incidence and clinical significance of slower ventricular tachycardias (VTs) in these patients remains largely unknown, though clinically important for device selection, programming, and follow-up. We prospectively studied symptomatic heart failure patients with an indication for a primary prophylactic ICD with or without concomitant resynchronization therapy according to SCD-HeFT inclusion criteria. Devices were programmed to an additional monitor zone for slow VTs at heart rates 130-186 b.p.m. Two hundred consecutive patients (86% male) were followed for a mean of 509 ± 308 days. One hundred and thirty-seven patients (68.5%) were New York Heart Association class III, 75 patients (37.5%) were on cardiac resynchronization therapy, and 124 (62%) had ischaemic cardiomyopathy. We observed 473 VT episodes in 36 patients (18%) and 131 ventricular fibrillation episodes in 30 patients (15%). Ventricular tachycardia overall occurred in 40 patients (20%). The incidence of slow VTs was low in only 12 patients (6%). No patient with slow VT suffered from syncope, palpitation, or decompensation leading to hospitalization. We did not find any reliable predictor for increased long-term risk of slow VTs. Incidence of slow VTs in a typical heart failure population with primary prophylactic ICD-implantation ± resynchronization therapy is very low. Slow VTs detected in the ICD monitor zone remained clinically asymptomatic. Thus, single chamber and atriobiventricular ICDs with a VT/ventricular fibrillation zone of ≥ 187 b.p.m. and one burst before shock delivery might be sufficient and pragmatic for the vast majority of these patients.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis

It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.

Long‐Term Follow‐Up of Prophylactic Implantable Cardioverter‐Defibrillator–Only Therapy: Comparison of Ischemic and Nonischemic Heart Disease

The benefits of primary prophylactic implantable cardioverter-defibrillators (ICDs) are actually debated, as some drawbacks become more apparent and as the natural history of cardiac disease seems to improve. Therefore, contemporary follow-up data of non-trial populations treated according to current guidelines remain necessary. The aim of this study was to evaluate mortality and the occurrence of ICD interventions in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM) who received in the recent era a primary prophylactic ICD without resynchronization therapy. Survival and event-free rates from appropriate ICD therapy are different between ischemic and nonischemic ICD patients. Prospective cohort study of 427 consecutive primary prevention ICD patients with ischemic or nonischemic heart disease, excluding patients with resynchronization. Ischemic heart disease was present in 290 patients (68%), nonischemic heart disease in 137 patients (32%). During a median follow-up of 31 months (interquartile range [IQR] 15-45 months), 30 patients (7%) died. Mortality was not different in both disease categories. The incidence of appropriate ICD interventions was similar in CAD and DCM (23% vs 21%). Appropriate ICD intervention occurred more frequently in patients with atrial fibrillation (29% vs 19%). Inappropriate ICD intervention occurred in 11% of patients. The clinical course of ischemic and nonischemic heart disease patients treated with a primary prophylactic ICD is similar with respect to mortality and to appropriate and inappropriate ICD interventions, in spite of a younger age at baseline of the DCM patients.

Effectiveness of prophylactic implantation of cardioverter-defibrillators without cardiac resynchronization therapy in patients with ischaemic or non-ischaemic heart disease: a systematic review and meta-analysis

AimsMuch controversy exists concerning the efficacy of primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with low ejection fraction due to coronary artery disease (CAD) or dilated cardiomyopathy (DCM). This is also related to the bias created by function improving interventions added to ICD therapy, e.g. resynchronization therapy. The aim was to investigate the efficacy of ICD-only therapy in primary prevention in patients with CAD or DCM.Methods and resultsPublic domain databases, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, were searched from 1980 to 2009 for randomized clinical trials of ICD vs. conventional therapy. Two investigators independently abstracted the data. Pooled estimates were calculated using both fixed-effects and random-effects models. Eight trials were included in the final analysis (5343 patients). Implantable cardioverter-defibrillators significantly reduced the arrhythmic mortality [relative risk (RR): 0.40; 95% confidence interval (CI): 0.27–0.67] and all-cause mortality (RR: 0.73; 95% CI: 0.64–0.82). Regardless of aetiology of heart disease, ICD benefit was similar for CAD (RR: 0.67; 95% CI: 0.51–0.88) vs. DCM (RR: 0.74; 95% CI: 0.59–0.93).ConclusionsThe results of this meta-analysis provide strong evidence for the beneficial effect of ICD-only therapy on the survival of patients with ischaemic or non-ischaemic heart disease, with a left ventricular ejection fraction ≤35%, if they are 40 days from myocardial infarction and ≥3 months from a coronary revascularization procedure.

Outcomes in heart failure patients referred for consideration of implantable cardioverter defibrillator for primary prophylaxis of sudden cardiac death: What are the risks of waiting?

Clinical trials have confirmed that implantable cardioverter defibrillators (ICDs) reduce mortality in patients with a left ventricular ejection fraction below 30%. The 'real-world' prognosis before ICD implantation in such patients is not known. The estimated risk of death is 0.8% per month, and this forms the basis for wait-time recommendations. To determine the consequences of waiting for ICD implantation among heart failure patients eligible for primary prophylactic ICD. The present retrospective study evaluated consecutive patients who were deemed eligible for primary prophylactic ICD implantation. Survival outcomes were tracked for patients who declined an ICD, those who accepted and received an ICD, and patients who accepted an ICD but died while waiting. Of 470 patients referred for evaluation, 218 were deemed eligible for an ICD. A total of 174 of 218 patients (79.8%) accepted an ICD; 39 (17.9%) declined, and five (2.3%) were deemed to be at too great a risk for the procedure. The mortality rate at two years among patients who accepted an ICD was 18.8% before ICD implantation and 12.2% after ICD implantation. Among patients who declined ICD implantation, the two year mortality rate was 5.3%. Among patients waiting for an ICD, five of 19 deaths were out-of- hospital sudden deaths. Of 12 patients who died after ICD implantation, there were no documented out-of-hospital sudden deaths. Consistent with current estimates, the mortality rate at two years among patients who accepted and were waiting for an ICD implant was 18.8%. After receiving an ICD, the mortality rate was 12.2% at two years.

Editorial: The economical challenge in the treatment of chronic heart failure: is primary prophylactic implantable cardioverter defibrillator therapy cost-effective in Europe?

We read with interest the editorial commenting on our modelling of the cost-effectiveness of primary prophylactic implantable cardioverter defibrillator (ICD) implantation according to the current European guidelines in a European population,1 claiming that our analysis overstated the likely cost-effectiveness of such therapy due to inappropriate assumptions around key determinants of cost and efficacy. Meine et al. mistakenly suggest that the results of our analysis2 were materially different from those from the MADIT II3 and SCD-HeFT4 trials. Our analysis had a life-time model time horizon (as recommended in most recent national and international guidelines for health economic analyses5–7), whereas the two US cost-effectiveness analyses took a (rather arbitrary) 12-year time horizon. If we had taken this time horizon, the incremental cost-effectiveness ratio (ICER) at that point in our analysis would have been €43 752 ($61 253 per QALY at exchange rate of €1: $1.40), similar to the MADIT II ($78 600–$114 000 per life year) and SCD-HeFT analyses ($58 510 per QALY). The more appropriate life-time horizon in our analysis gave an ICER of €31 717 per QALY gained ($44 404). The editorial also suggests that there is a lack of a treatment effect for ICDs in …

Venturing Into the Storm

Estimates of the incidence of electrical storm (ES) range from 4% over 20.6 months of follow-up in patients with primary prophylactic implantable cardioverter-defibrillators (ICDs)1 to 20% over 31 months of follow-up in a population with secondary prophylactic ICDs.2 Although smaller observational series have not identified a clear mortality risk associated with ES,3,4 larger and more recent series have suggested a large and significant association between repeated ventricular arrhythmic events and death, both sudden and nonsudden.5–8 It is unclear whether this adverse outcome is a result of repeated ICD shocks or whether recurrent arrhythmias are a marker of sicker hearts that are destined to do poorly. Indeed, the mode of death after ES frequently is related to heart failure. Uncertainty has thus remained about whether interventions for ES can influence mortality beyond the acute period.9 In this issue of Circulation , Carbucicchio and colleagues10 describe a large series of …

Risk stratification and prevention of sudden death in hypertrophic cardiomyopathy

Sudden cardiac death is the most devastating manifestation of hypertrophic cardiomyopathy (HCM) and often occurs in young and previously asymptomatic patients. Therefore, risk stratification for sudden death has a major role in the management of HCM and has acquired even greater relevance since the implantable cardioverter-defibrillator (ICD) has proved to be highly effective in preventing sudden death in this disease. The ICD is definitely indicated for secondary prevention of sudden death in patients with HCM who have survived a cardiac arrest with documented ventricular fibrillation, or experienced one or more episodes of sustained ventricular tachycardia. However, uncertainties persist regarding the precise selection of patients for primary prophylactic ICD implantation. A number of risk markers are used to assess the magnitude of risk, including family history of premature sudden death; extreme left ventricular (LV) hypertrophy (> 30 mm) in young patients; nonsustained ventricular tachycardia on Holter electrocardiographic recording; unexplained (not neurally mediated) syncope, particularly in young patients; and blood pressure decrease or inadequate increase during upright exercise. Multiple risk factors convey a definite increase in risk. However, a single risk factor such as family history of multiple sudden deaths, massive LV hypertrophy in a young patient, or frequent and/or prolonged runs of nonsustained ventricular tachycardia on Holter, may also justify consideration of a prophylactic ICD.

Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome

Aims To analyse the follow-up data of implantable cardioverter-defibrillator (ICD) therapy in Brugada syndrome (BS). Methods and results We conducted a retrospective, single centre study of 47 patients (mean age: 44.5 ± 15 years) with BS, who underwent primary prophylactic ICD implantation. All patients had baseline spontaneous (23 patients) or drug-induced (24 patients) coved type I ECG pattern. All patients were judged to be at high risk because of syncope (26 patients) and/or a positive family history of sudden death (26 patients). During a median follow-up of 47.5 months, seven patients had appropriate shocks. The presence of spontaneous type I ECG and non-sustained ventricular tachyarrhythmia in the ICD datalog suggested a trend towards shorter appropriate shock-free survival by Kaplan–Meier analysis ( P = 0.037 and P = 0.012, respectively). Seventeen patients received inappropriate shocks (IS); eight patients for sinus tachycardia; six patients for new onset atrial arrhythmias; and five patients for noise oversensing. In multivariable Cox-regression analysis, new onset atrial fibrillation (AF) and less than 50 years of age were independent predictors of significantly shorter IS-free survival ( P = 0.04 and P = 0.036, respectively). Conclusion In high-risk patients with BS, primary prophylactic ICD therapy is an effective treatment. In this, young and otherwise healthy patient population, the IS rate is high.

Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome: reply

Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome: reply

Comparison of N-Terminal Pro-Brain Natriuretic Peptide Versus Electrophysiologic Study for Predicting Future Outcomes in Patients With an Implantable Cardioverter Defibrillator After Myocardial Infarction

The aim of the study was to examine the predictive value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) versus electrophysiologic study in patients with implantable cardioverter-defibrillators (ICDs) after myocardial infarction (MI). We prospectively studied 99 consecutive patients with a history of MI who underwent ICD implantation for primary or secondary prevention of sudden cardiac death. An electrophysiologic study was performed in all patients. Venous blood samples for NT-pro-BNP measurement were obtained at the beginning of the study. The primary end point was ventricular tachycardia or ventricular fibrillation (VT/VF) and the secondary end point was a composite of death, hospitalization for heart failure, or MI. On multivariate Cox regression analysis, NT-pro-BNP level at or greater than median (497 ng/L) was the only significant predictor for VT/VF occurrence (p = 0.047). Along with amiodarone use (p = 0.001), NT-pro-BNP levels higher than median were also associated with a higher risk of composite clinical events (p = 0.036). Kaplan-Meier analysis showed that patients with NT-pro-BNP level at or greater than median had a higher risk of experiencing VT/VF and composite clinical events than patients with NT-pro-BNP levels less than median (log-rank p <0.05). In conclusion, assay of NT-pro-BNP, which is easy to perform and widely available, is superior to electrophysiologic study for prediction of future outcomes in predominantly secondary prophylactic ICD recipients after MI. In the era of primary prophylactic ICD implantation without preimplantation electrophysiologic study, higher NT-pro-BNP levels might help to improve risk-adjusted concomitant antiarrhythmic therapy and device selection.

Uncertainty on the Use of Aldosterone Antagonists for Primary Therapy for Sudden Cardiac Death in the Setting of Implanted Devices

In the early development of therapy for acute myocardial infarction, it was thought that once the necrotic process had been completed (usually within 24 hours of coronary artery occlusion), additional therapies could not affect outcome. However, after completion of the necrotic process, the myocardial infarction may thin and stretch (involving lengthwise slippage of myocytes), a phenomenon referred to as myocardial infarct expansion. This process causes local left ventricular cavity dilatation followed by gradual global left ventricular dilatation and lengthwise (eccentric) hypertrophy of the noninfarcted tissue. Apoptosis (programmed cell death) and some attempt of the myocardium to regenerate, especially at the infarct border zone, may also contribute to this remodeling process of the ventricle. If the left ventricle remodels in such a way that it becomes very dilated, then the prognosis is poor, and heart failure is more likely to occur.1 These later processes of myocardial infarct expansion and left ventricular remodeling became the target of therapies such as angiotensin-converting enzyme (ACE) inhibition that could be initiated after 24 hours of coronary occlusion. ACE inhibition, angiotensin receptor blockade, and long-term β-blockade have become standard pharmacological approaches for postinfarction left ventricular dysfunction and heart failure. Response by Pitt and Pitt p 2989 Ventricular arrhythmias can occur in both the acute and chronic phases of acute myocardial infarction and can lead to sudden cardiac death (SCD). Reentrant arrhythmias may arise at the border zone of infarcts, causing monomorphic ventricular tachycardia that may occur years after the index infarction. Recurrent myocardial ischemia resulting in an unstable substrate may contribute to polymorphic ventricular tachycardia or ventricular fibrillation. Agents such as β-blockers that are anti-ischemic may reduce sudden death by quieting this unstable substrate. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable defibrillators were shown to reduce mortality in post–myocardial infarction patients with …

Long-term follow-up of primary prophylactic implantable cardioverter-defibrillator therapy in Brugada syndrome

To analyse the follow-up data of implantable cardioverter-defibrillator (ICD) therapy in Brugada syndrome (BS). We conducted a retrospective, single centre study of 47 patients (mean age: 44.5 +/- 15 years) with BS, who underwent primary prophylactic ICD implantation. All patients had baseline spontaneous (23 patients) or drug-induced (24 patients) coved type I ECG pattern. All patients were judged to be at high risk because of syncope (26 patients) and/or a positive family history of sudden death (26 patients). During a median follow-up of 47.5 months, seven patients had appropriate shocks. The presence of spontaneous type I ECG and non-sustained ventricular tachyarrhythmia in the ICD datalog suggested a trend towards shorter appropriate shock-free survival by Kaplan-Meier analysis (P = 0.037 and P = 0.012, respectively). Seventeen patients received inappropriate shocks (IS); eight patients for sinus tachycardia; six patients for new onset atrial arrhythmias; and five patients for noise oversensing. In multivariable Cox-regression analysis, new onset atrial fibrillation (AF) and less than 50 years of age were independent predictors of significantly shorter IS-free survival (P = 0.04 and P = 0.036, respectively). In high-risk patients with BS, primary prophylactic ICD therapy is an effective treatment. In this, young and otherwise healthy patient population, the IS rate is high.

Impact of Implantable Defibrillators and Resynchronization Therapy on Outcome in Patients with Left Ventricular Dysfunction – A Meta-Analysis

Background: The clinical benefits of cardiac resynchronization therapy (CRT) and primary prophylactic implantable cardioverter defibrillator (ICD) in patients with left ventricular systolic dysfunction (LVSD) are debated. Objective: To evaluate by a meta-analysis the effect of CRT and prophylactic ICD therapy in patients with LVSD. Methods: Eligible trials evaluating the effect of CRT vs. no-CRT, ICD vs. no-ICD and adding ICD to CRT vs. no-ICD were selected and meta-analyzed. The outcomes were: all cause mortality, cardiac mortality, hospitalization for heart failure and change in exercise tolerance and New York Heart Association class. Results: Implantation of CRT reduced all cause mortality odds ratio (OR) = 0.73 (0.60–0.89) p = 0.002 and hospitalization for heart failure OR = 0.60 (0.45, 0.80) p = 0.001, increased peak oxygen consumption by 1.77 (0.32–3.22) ml/kg/min p = 0.017 and improved New York Heart Association class by at least one class with OR = 1.52 (1.30, 1.77) p < 0.0001. Implantation of ICD reduced all-cause mortality OR = 0.75 (0.59–0.96) p = 0.025 and cardiac mortality OR = 0.63 (0.48, 0.82) p = 0.001. Adding ICD to CRT reduced all cause mortality OR = 0.69 (0.53–0.91) p = 0.008. Conclusion: Selective patients with LVSD benefit from CRT, ICD or both. Further investigations are necessary to clarify which patients benefit most from a single or combined device implantation.