Most Important Outcomes Research Papers on Device Therapies for Cardiomyopathies

Abstract

HomeCirculation: Cardiovascular Quality and OutcomesVol. 6, No. 5Most Important Outcomes Research Papers on Device Therapies for Cardiomyopathies Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBMost Important Outcomes Research Papers on Device Therapies for Cardiomyopathies Aakriti Gupta, MBBS, Kumar Dharmarajan, MD, MBA, Rachel Dreyer, PhD, Behnood Bikdeli, MD, Ruijun Chen, BA, Vivek T. Kulkarni, AB, Ruizhi Shi, MD, MPH, Abbas Shojaee, MD and Isuru Ranasinghe, MBChB, MMed, PhDfor The Editor Aakriti GuptaAakriti Gupta Search for more papers by this author , Kumar DharmarajanKumar Dharmarajan Search for more papers by this author , Rachel DreyerRachel Dreyer Search for more papers by this author , Behnood BikdeliBehnood Bikdeli Search for more papers by this author , Ruijun ChenRuijun Chen Search for more papers by this author , Vivek T. KulkarniVivek T. Kulkarni Search for more papers by this author , Ruizhi ShiRuizhi Shi Search for more papers by this author , Abbas ShojaeeAbbas Shojaee Search for more papers by this author and Isuru RanasingheIsuru Ranasinghe Search for more papers by this author and for The Editor Originally published1 Sep 2013https://doi.org/10.1161/CIRCOUTCOMES.113.000556Circulation: Cardiovascular Quality and Outcomes. 2013;6:e36–e47Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 IntroductionDisorders of the cardiac muscle or cardiomyopathies are a broad, yet collectively common, group of conditions. Despite the heterogeneous etiologies, mode of death from these conditions is remarkably similar - progressive decline in cardiac function leading to intractable heart failure (HF) and sustained ventricular arrhythmias resulting in sudden cardiac death (SCD). Nearly 50% of patients die within 5 years of a HF diagnosis.1 Indeed, in the United States, HF alone is thought to cause 55,000 deaths per year2 and further contribute to 1 in 9 deaths overall.1 However, while advanced HF and the risk of SCD were once thought to be untreatable, technological advances has seen the emergence of device therapies as viable treatment options. Specifically, implantable cardioverter-defibrillator (ICD) therapy for treatment of ventricular arrhythmias, cardiac resynchronization therapy (CRT) for restoring cardiac synchrony and mechanical efficiency, and ventricular assist device (VAD) therapy to temporarily or permanently replace the function of the failing heart, have all emerged as highly efficacious therapies.The expanding use of device therapies, however, poses many challenges. First, while the indications for these devices are well summarized in clinical guidelines,3,4 considerable hurdles remain in ensuring eligible patients receive these therapies.5 By the same token, establishing the safety and effectiveness of these therapies in populations that are found in clinical practice, yet commonly excluded from trials, such as the elderly6 and uncommon forms of cardiomyopathies,7 is a high priority. Second, rapid dissemination of technologies frequently results in disparities in care. Indeed, age, gender, and racial disparities, in both receipt of these devices and outcomes following implantation, have been well documented. Whether these disparities have persisted, and the potential causative mechanisms underlying these disparities, however, are uncertain.8,9 Third, these devices are not without significant untoward effects; understanding and minimizing these adverse events, and in particular long-term events, is important particularly in the context of improving patient survival.10 For example, patient longevity now often exceeds that of ICD’s and 70% of patients are expected to require an ICD replacement in their lifetime exposing patients to risks from multiple surgical procedures.11 Similarly, VADs are increasingly used as long-term destination therapy. Fourth, while considerable focus has centered on establishing the effectiveness of these therapies, the impact of these devices on patient reported outcome such as symptoms, function, and quality of life have been rarely examined.12 Lastly, these devices are costly; establishing the cost- effectiveness of these devices is an essential prerequisite in an era of constrained healthcare resources.13We focus predominantly on papers that address these challenges in the following topic review for Circulation: Cardiovascular Quality and Outcomes. We have therefore included papers that evaluate outcomes related to (1) implanted cardioverter-defibrillators, (2) cardiac-resynchronization therapy and (3) ventricular assist devices in patients with cardiomyopathies and its common presentations of heart failure and sudden cardiac death.Temporal Trends in Treatment and Outcomes for Advanced Heart Failure With Reduced Ejection Fraction From 1993 to 2010: Findings From a University Referral CenterSummary: The effectiveness of change in management of severe HF during past 20 years is uncertain. Using data from a single tertiary referral center, the authors conducted an observational study to compare the outcomes of patients (n=2057) with advanced HF (EF ≤40%) over three 6-year periods during which, HF therapies were evolving (1993 to 1998, 1999 to 2004, 2005 to 2010). The primary outcome was all-cause mortality and the secondary outcomes were sudden death, progressive HF death, VAD therapy, urgent transplantation, and their combination. All outcomes were assessed at 1, 2, and 3 years. The proportion of patients receiving ICD therapy (increase from 11.1% to 65.7%) and CRT therapy (increase from 0% to 39%) were substantially higher in the latter periods (both P<0.001). A concurrent increase in use of aldosterone antagonists and β-blockers was noted, while the rate of anticoagulation therapy was unchanged and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers remained at a high level across the eras. Fewer patients used nitrates, hydralazine, and loop diuretics in latter periods. Risk-adjusted analysis for predictors of HF mortality showed that years 2005–2010 were associated with 42% lower relative risk of all-cause mortality during 3-year follow-up (HR, 0.58; 95% CI, 0.40–0.85) with a trend towards a decreased risk of sudden death (P=0.057) compared with earlier eras. In later periods, increased rates of HF deaths, transplants, and VADs were observed perhaps because of different risk profiles at the time of referral and substantial reductions in sudden death. Also later periods were not independently associated with risk of progressive HF death but period 2 had a higher risk of the combined end point of mortality, urgent transplant, or VAD.Conclusion: This study shows promising improvement in patient outcomes over time which have occurred in parallel with advancements in management of HF. Device therapies, particularly ICD and CRT therapies, have increased markedly which may partially explain the reduction in SCD. It is important to note that these findings are from a single tertiary referral center with an advanced HF program and thus may not be able to generalize to other settings. Nevertheless, this study shows the successful transition from clinical trial to real-world populations for life-prolonging medications and devices for patients with advanced HF over the past 2 decades. Yet, despite survival improvements, all-cause mortality rate remains high (≈30%) among HF patients with reduced EF, indicating the need of new treatment options and management strategies to decrease overall mortality.14Implantable Cardioverter-Defibrillator TherapyThe first successful placement of the ICD in 1980, and subsequent FDA approval in 1985, revolutionized the management of individuals at high risk of sudden cardiac death (SCD).15 From the large device that required to be implanted abdominally with no programmability to a sleek pectoral implant with extensive programmability, tremendous strides have been made in the evolution of ICD technology. Multiple randomized trials demonstrating its high success rate in terminating ventricular fibrillation (VF) and ventricular tachycardia (VT) and improved survival have led ICD implantation to be considered as first line treatment option for the secondary prevention of SCD.16–18 Indications for ICD placement have also expanded to include populations at high risk of SCD due to VT/VF for primary prevention following the landmark trials including MADIT I and MADIT II and SCD-HeFT that demonstrated improved survival with prophylactic ICD placement in selected patients with left ventricular systolic dysfunction.19–21 From January 1, 2006, through December 31, 2009, 486,025 ICD implants were documented in the ICD Registry of the National Cardiovascular Data Registry (NCDR), which is estimated to account for 90% of all ICDs implanted in the United States during this period.22The life-prolonging benefit derived from ICDs however comes with several strings attached. With the rapidly increasing placement of ICDs, consequences of inappropriate ICD shocks have received greater attention. As many as 1 in 3 of these patients suffer inappropriate shocks,23 which have been associated with poor mental and physical functioning, psychological disorders including anxiety and depression, and increased risk of HF hospitalizations.24,25 In fact, patients with psychological disorders at baseline have been noted to be at higher risk of worse outcomes from ICD placement.26 Furthermore, an estimated 18% of patients have an implant-related adverse event and many are exposed to lead and generator related complications long-term.27,28 Moreover, elderly patients with multiple comorbidities may not derive equal benefit from ICD therapy, given the higher risks of non-cardiac causes of death.29 Similarly, it has also been debated that women may derive less benefit from ICD therapy as compared with women for reasons not entirely understood. The establishment of the ICD Registry by the American College of Cardiology NCDR in conjunction with the Heart Rhythm Society is an important initiative that will permit the collection of comprehensive data on ICD implantations and long-term outcomes.The following summaries concern multiple topics pertinent to ICD therapy including trends in implantation over time, gender-, race- and age- related differences in implantation and outcomes, predictors of short- and long-term complications, and methods to improve patient selection.Implantable Cardioverter-Defibrillators Have Reduced the Incidence of Resuscitation for Out-of-Hospital Cardiac Arrest Caused by Lethal ArrhythmiasSummary: The authors sought to establish the contribution of ICD therapy to the decline in ventricular fibrillation (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac arrest (OHCA) in recent years. Using a prospective database of all OHCA resuscitation in the province of North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), they compared VF OHCA incidence (per 100 000 inhabitants per year) collected in 2005–2008 with VF OHCA incidence data during 1995–1997. They also collected ICD interrogations of all ICD patients from North Holland and identified all appropriate ICD shocks in 2005–2008. The number of prevented VF OHCA episodes was calculated, considering that only some of the appropriate shocks would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100 000 in 1995–1997 to 17.4/100 000 in 2005–2008 (P<0.001). Non-VF OHCA increased from 12.2/100 000 to 19.4/100 000 (P<0.001). VF as presenting rhythm declined from 63% to 47%. In 2005–2008, 1972 ICD patients received 977 shocks. Of these shocks, 339 were caused by a life-threatening arrhythmia. They estimated that these 339 shocks prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA, corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF OHCA incidence.Conclusion: Findings from this study that ICD therapy may explain up to one-third of the observed decline in VF OHCAs in North Holland could potentially be extrapolated to the US where a similar decline has been registered.30,31 Besides ICD therapy, other studies have noted factors like beta-blocker use, overall decline in coronary heart disease burden and increasing conversion of VF to asystole rhythm at the time of detection to contribute to this trend.32 Of note, an increase in non-VF OHCA was noted through the study period concerning for shifts in patient and treatment characteristics. Nonetheless, improved identification of candidates for device therapy, better medical therapy for patients with cardiac disease and augmentation of resuscitative efforts may lead to continued declines in VF OHCAs and overall SCD rates.33Use of Primary Prevention Implantable Cardioverter-Defibrillators in a Population-Based Cohort Is Associated With a Significant Survival BenefitSummary: Although clinical trials have demonstrated survival benefit from ICD implantation for primary prevention, they may not accurately reflect morbidity and mortality outcomes in the real world population that may be eligible for this therapy. The authors sought to determine the utilization rates of implantable defibrillators in a primary prevention ICD-eligible population and mortality in this group compared with a group that had undergone implantation of this therapy. A retrospective cohort of patients from April 1, 2006, to December 31, 2009, was used to define a primary prevention ICD-eligible population. The two groups were compared on the basis of ICD implantation (no-ICD versus ICD) and the primary outcome measure was mortality. Of the 717 patients found to be potentially eligible for a primary prevention ICD, only 116 (16%) were referred. The remaining cohort of 601 patients were compared with an existing cohort of primary prevention ICD patients (n=290). A significant survival benefit was associated with primary prevention ICD implantation (HR, 0.46; 95% CI 0.33–0.64). When adjusted for pre-specified variables known to be associated with overall mortality and propensity score for ICD use, a similar survival benefit was seen (HR, 0.59; 95%CI 0.40–0.87).Conclusion: Despite the class IA AHA recommendation for primary prevention ICD implantation, only a small percentage of the eligible population in this registry study from Canada received the device, supporting results from other studies in the US8 where observed adherence to this particular guideline was low. Notably, the authors of this study demonstrated the translation of clinical trial results,20,21 which showed survival benefit with use of primary prevention ICDs, into real world practice. Given that patients receiving ICD therapy in clinical practice are much older and sicker than the clinical trial population of the SCD-HeFT and MADDIT-II studies,20–22 and the high cost of this procedure, findings from this study are reassuring. Implementation of point-of-care tools that help identify and risk-stratify candidates for this technology will help promote evidence-based decision making in real world practice.34Extent of and Reasons for Nonuse of Implantable Cardioverter Defibrillator Devices in Clinical Practice Among Eligible Patients With Left Ventricular Systolic DysfunctionSummary: Previous claims and registry data have shown that 40–80% of eligible patients do not receive an implantable cardioverter defibrillator (ICD).35,36 Using detailed chart abstraction, LaPointe and colleagues determined the extent and reasons for nonuse of ICDs among patients with HF with reduced ejection fraction at a tertiary academic medical center. They included hospitalized patients with HF between January 1 and August 30, 2007 and determined whether each patient had an ICD during a subsequent 1-year period. From the 542 included patients, 224 (41%) did not have and ICD placed up to 1 year after index hospitalization. In the initial analyses, absence of ventricular arrhythmia or cardiac arrest (OR: 3.17; 95% CI: 2.14 to 4.68), index hospitalization on a noncardiology service (OR: 2.64; 95% CI: 1.65 to 4.21), and female sex (OR: 1.90; 95% CI: 1.28 to 2.81) were the main factors associated with increased likelihood of ICD non-use. Chart review showed that from the 224 ICD nonusers, 117 had contraindications to ICD and 38 patients refused it, leaving only 69 truly eligible patients who did not receive an ICD. Among these 69 patients, absence of ventricular arrhythmias, non-cardiology hospital service, and lack of health insurance, but not the female sex, were associated with increased likelihood of ICD nonuse.Conclusion: This study had several interesting findings. First, it showed that while there is room to improve ICD use, true rate of ICD underuse might be markedly lower than what has been previously reported. Further, contrary to prior studies,37 female sex was not a predictor of ICD nonuse among truly eligible patients. However, the data for this study were from a leading academic medical center. Overall rate of ICD underuse and associated disparities might be more notable at other medical centers in underserved areas.38Use of a Screening Tool Improves Appropriate Referral to an Electrophysiologist for Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac DeathSummary: It is known that implantable cardioverter defibrillators (ICDs) are underused for primary prevention in at-risk patients, despite the existence of guideline recommendations and coverage by insurers. The authors determined whether using a screening tool in two primary care practices would improve the appropriate identification and referrals for ICD placement. They compared the number and proportion of appropriate referrals before versus after use of the screening tool. The proportion of eligible patients who were referred increased during the post-screening period at both sites (21/35 to 44/44, P<0.001 and 5/15 to 8/10, P<0.02). From the total of 78 patients referred in the entire study period, 32 were accepted for ICD placement.Conclusion: Irrespective of mechanism, including a Hawthorne effect, this study suggests that using a screening tool might enhance the referrals for ICD placement among at-risk patients. However, this interesting study has some limitations, including the before and after study design, and use of temporally displaced cohorts. Nevertheless, this study highlights the need for identification and addressing the barriers for referral, including physician and patient factors, in future studies may improve the use of ICDs among at-risk patients.5Important Differences in Mode of Death Between Men and Women With Heart Failure Who Would Qualify for a Primary Prevention Implantable Cardioverter-DefibrillatorSummary: Recent meta-analyses have suggested that women receiving a primary prevention ICD may not derive similar benefit as men.39–41 To explore this topic further, the authors examined whether sex differences exist in the mode of death among a large cohort of ambulatory HF patients meeting criteria for a primary prevention ICD, in particular, whether women are less likely to die of sudden cardiac death. They used a participant-level de-identified database of ambulatory HF patients from 5 randomized trials or HF registries. From this database, the authors included patients meeting criteria for primary prevention ICD including New York Heart Association Class II/III HF and left ventricular ejection fraction < 35%. Risk of death was calculated using the Seattle Heart Failure Model (SHFM). For those who did die, cause of death was categorized as sudden death, pump failure death, or other death. From 8,337 patients (20% women), the authors found that all-cause mortality at 2.4 years was 26.3%, of which 40% was due to sudden death and 30% was due to pump failure. Adjusted all-cause mortality was 24% lower for women. Among causes of death, sudden death was 31% lower for women. This pattern of lower risk of sudden death among women was present for patients with low, intermediate, and high-risk SHFM scores.Conclusion: In finding that deaths among women qualifying for a primary prevention ICD are less often sudden than among men, the authors demonstrate a potential explanation for the observation that women are less likely to derive a mortality benefit from ICD treatment. The reasons for this difference are not further explored in this paper, though may relate to the fact that women in the study were less likely to have an ischemic etiology of their HF (43% in women versus 59% in men). The study conclusions must be interpreted in light of the fact that the post-hoc assignment of mode of death is subject to error. In addition, all sudden deaths cannot be presumed to arise from a cardiac cause as may be implied by this paper.42Trends in Use of Implantable Cardioverter-Defibrillator Therapy Among Patients Hospitalized for Heart Failure: Have the Previously Observed Sex and Racial Disparities Changed Over Time?Summary: It has been reported that certain minorities such as women and blacks receive low utilization rates of ICDs for primary prevention.37,43,44 Within the observed sex and race disparities it is uncertain whether the use of ICD device therapy has altered over time. In this study, the authors determined the rate of ICD implantation use per year for both, the overall population and for sex and race subgroups, using patients enrolled in the Get with the Guidelines-Heart Failure (GWTG-HF) program between 2005–2009 (N=11,880, 36% women).44 Patients ≥65 years old with a history of HF and left ventricular ejection fraction (LVEF) ≤35% were included in this study. Patients were excluded if they had new-onset HF, no documented LVEF or an LVEF >35%, had a contraindication for not receiving ICD treatment, or if they had missing data on sex and race. GWTG-HF files were then matched with enrollment details and in-patient claims from the Centers for Medicare and Medicaid Services (CMS) data to identify unique patients (matched by admission/discharge date, date of birth, sex and hospital). Over the study period, the most significant increase in ICD therapy was observed from 2005–2007 (increased from 30–42%) and then remained constant from 2008–2009. In multivariate analyses, ICD use significantly increased in all 4 sex/race groups including the overall population (OR 1.28; 95% CI, 1.11–1.48 per year; P=0.0008), black women (OR 1.82; 95% CI, 1.28–2.58 per year; P=0.0008), white women (OR 1.30; 95% CI 1.06–1.59 per year; P=0.0010), black men (OR 1.54; 95% CI 1.19–1.99 per year; P=0.0009), and white men (OR 1.25; 95% CI, 1.06–1.48 per year, P=0.0072), even following adjustment for important confounders. However, the increase in ICD use was the greatest among blacks but persisted among women over time.Conclusion: Despite the previously reported underutilization of ICD therapy in eligible patients, the rate of this guideline-recommended therapy has promisingly increased both over time and between all sex/race groups. Although race differences were no longer present by the end of the study period, sex differences in ICD use persisted. The GWTG registry, however, only captures those patients hospitalized for HF and thus assessment of ICD use is limited to this particular setting. In addition, this GWTG program largely attracts hospitals with a focus on quality improvement and therefore the results of this study may not be generalizable to other clinical practices. Nevertheless, while racial disparities in ICD utilization are no longer present, significant sex disparities in treatment still exist. Future studies should focus on assessing gender differences in the underuse of ICD therapy and persistence in its use over time on patient outcomes.8Predictors of Short-Term Complications After Implantable Cardioverter-Defibrillator Replacement: Results From the Ontario ICD DatabaseSummary: ICD device replacements have been linked to an increased risk of complications.45–47 This study examines both the frequency and predictors of complications after ICD device replacement. The authors enrolled patients ≥18 years from 18 centers undergoing ICD generator replacement in the prospective Ontario Implantable Cardioverter Defibrillator registry from 2007–2009 (N=1081, 21% women).48,49 During ICD clinic visits, all patients were routinely assessed for 45-day device-related difficulties that were further classified as either major or minor. Within this study, 21% of patients received an ICD replacement and 4.3% of patients had a complication rate within 45 days, with a total of 47 major complications in 2.6% of individuals (infection, lead revision, electrical storm and pulmonary edema). Furthermore, 41 minor complications occurred in 2.3% of patients (incisional infection, pocket hematoma). In multivariate models, the Canadian Cardiovascular Society Angina class (CCSAC) ≥2 (adjusted HR 3.70, 95% CI 1.16–11.81) was associated with a statistically significant risk of major adverse complications. In addition, independent risk factors related to any complication included anti-arrhythmic therapy (HR 6.29, P <0.001), implanter volume (HR 10.4 for <60/y versus >120/y, P=0.026) and CCSAC ≥2 (HR 3.00, P=0.031). Lastly, major complications following ICD replacement were associated with a significant risk of mortality at all time points including 45, 90 and 180 days (HR, 9.61, 12.69, 6.41, all P <0.05).Conclusion: The current study suggests that complications following ICD replacement are driven by three major components including device, physician and patient factors. Complications following ICD replacement have a detrimental effect on patient outcomes and are likely to contribute substantially to the length of hospital stay and increase health care costs. Several limitations of this study should be addressed in light of these findings. Firstly, although several important risk factors were identified, which may be biologically plausible, the potential mechanism could not be pinpointed in this study. Secondly, although this study presents a modest number of patients with ICD replacement complications, the number of events and patients affected are quite small, thus limiting the power of the analysis. These ICD replacements may pose a higher risk than new implants, which calls for the development of longer lasting devices, the reduction of battery drain and/or replacing normally functioning components.50Influence of Age on Perioperative Complications Among Patients Undergoing Implantable Cardioverter-Defibrillators for Primary Prevention in the United StatesSummary: The periprocedural complication rates for ICD therapy among the elderly are helpful for patients to assess risks with ICD implantation and make an informed clinical decision, but such data are insufficient in most ICD trials. This study determines the effect of age on ICD implantation-related complications and mortality across different communities in the United States. Using a national registry database, patients undergoing ICD implantation for primary prevention from January 2006 to December 2008 were included. The primary outcome was in-hospital complications including death. Age was categorized into 5 groups (65, 65 to 69, 70 to 74, 75 to 79, 80 to 84, and at least 85 years old). The study results showed that the complications rate of the entire cohort was approximately 3.4%, including death, after ICD implant. The complications rate increased with age (from 2.8% of patients < 65 years old to 4.5% of patients 85 years and older). Compared with patients < 65 years old, the odds of any adverse event or death after adjustment for clinical covariates were 1.14 (95% CI, 1.03 - 1.25) among 75- to 79-year-olds, 1.22 (95% CI, 1.10 - 1.36) among 80-to 84-year-olds, and 1.15 (95% CI, 1.01 - 1.32) among patients >85 years. Besides advanced age, comorbidities, including end-stage renal disease, stage IV HF, atrial fibrillation, and advanced heart block, were associated with an increased risk of complications.Conclusion: Besides a modestly increased risk of periprocedural complications and in-hospital mortality among older patients who undertook ICD implantation, this well conducted study also identified comorbidities, including multiple cardiac and non-cardiac conditions, which independently increased the risk of perioperative complications. This suggests the need to consider for both comorbidities and age when evaluating potential risk of complications. Importantly, the ICD complications rates in this study, even for the oldest patients, were reassuringly lower than rates observed in prior studies,27,51–54 which may be informative for risk benefit analysis in clinical practices.55Implantable Cardioverter Defibrillators in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Patient Outcomes, Incidence of Appropriate and Inappropriate Interventions, and ComplicationsSummary: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), an inherited disease characterized by dysfunction of the right ventricle and ventricular arrhythmias, is a common cause of sudden cardiac death (SCD) in young adults. ICDs are effective primary prevention and secondary prevention against sudden cardiac death (SCD), but a thorough understanding of the outcomes and complications of ICD therapy in these patients is lacking. The author of this study conducted a systematic review and meta-analysis of the available literature concerning the use of ICDs in patients with ARVD/C. Primary outcomes were cardiac mortality, non-cardiac mortality, appropriate ICD intervention, and inappropriate ICD intervention. A total of 24 studies wer