Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure

More than 4000 patients have been evaluated in randomized controlled trials of cardiac resynchronization therapy (CRT). These studies have demonstrated that CRT with or without an implantable cardioverter-defibrillator (ICD) consistently improves quality of life, functional status, exercise capacity, and cardiac structure and function and reduces morbidity and mortality in heart failure patients with ventricular dyssynchrony. The magnitude of benefit seen with CRT is comparable to or exceeds that seen with evidence-based drug therapies for heart failure but occurs in patients who are already receiving such medications. Thus, CRT has been added to the list of evidence-based therapies that make heart failure patients feel better and live longer (the Table). Consequently, a strong ethical mandate exists for the use of CRT in heart failure. This mandate is reflected in our current practice guidelines for the management of chronic heart failure, which state that all eligible patients should receive CRT unless contraindicated.1,2 End of debate! CRT should be a routine part of any evidence-based treatment regimen for heart failure. View this table: Major Benefits of Evidence-Based Heart Failure Therapies Of course, things are never quite so simple, so let us take a look at the evidence supporting this clinical mandate for CRT and address patient selection, some of the limitations of CRT, and some of the unanswered questions about the use of CRT in heart failure. None of this discussion will lessen the role of CRT in the treatment of heart failure; rather, it will guide the selection of appropriate patients and speculate on the future application of CRT to an even broader group of heart failure patients. Response by Greenberg and Mehra p 2698 Approximately one third of patients with systolic heart failure exhibit ventricular dyssynchrony, defined as a QRS duration >120 ms on the surface ECG.3,4 Ventricular dyssynchrony produces suboptimal ventricular …

Several studies have already established the superiority of cardiac resynchronisation therapy (CRT)-defibrillator (D) over implantable cardioverter-defibrillator (ICD) alone in patients with severely symptomatic chronic heart failure (New York Heart Association (NYHA) class III/IV), left ventricular (LV) systolic dysfunction, and a wide QRS complex. Synchronous pacing of opposing LV walls in malfunctioning asynchronously contracting LV regions creates resynchronisation with restoration of LV motion dynamics. In the Multicenter Automatic Defibrillator Implantation Trial-CRT (MADIT-CRT) study, a reduction in mortality or hospitalisation for congestive heart failure with CRT-D was observed compared with ICD. However, no difference in mortality was noted between the two groups. The COMPANION study established the superiority of CRT-D over optimal medical management alone in reducing all-cause mortality patients with NYHA class III/IV symptoms. While improvements in LV dimensions with CRT in patients with mildly asymptomatic heart failure were observed in the MIRACLE ICD-II and REVERSE trials, there were no significant differences in clinical endpoints in these studies. The MADIT-CRT study showed a significant reduction in the composite endpoint of mortality or heart failure events in similar patients with NYHA class I/II symptoms over a mean follow-up of 2 years. However, no significant difference in all-cause mortality between the two groups was noted. At the November 2010 meeting of the AHA in Chicago, the results of the Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) study were presented by Dr. Anthony Tang, Ottawa, Canada and recently published in the New England Journal of Medicine [1]. In the RAFT study, the safety and efficacy of CRT-D compared with ICD alone were investigated in patients with NYHA class II/III, LV systolic dysfunction (left ventricular ejection fraction (LVEF), ≤30%), and a wide QRS complex. All patients had been scheduled for ICD implantation for primary or secondary prevention of sudden cardiac death. The primary endpoint of the study was all-cause mortality or hospitalisation for worsening congestive heart failure. A total of 1798 patients (mean age, 66 years; 17% women) were randomised to either CRT-D (n = 894) or to ICD alone (n = 904). Two thirds of the patients had ischaemic cardiomyopathy. The majority of patients (80%) had NYHA class II and a mean LVEF of 22%. Permanent atrial fibrillation or flutter was seen in 13% of the patients. Patients were optimally treated, and the mean duration of follow-up was 40 months. Medtronic transvenous devices and leads were used in both groups. The LV lead was positioned in the lateral or posterolateral walls. Programming was set to minimise right ventricular pacing in the ICD arm and to maximise biventricular pacing in the CRT-D arm. The mean nonpaced QRS complex was 158 ms, and the mean paced QRS complex was 208 ms. A left bundle branch block (LBBB) pattern was noted in 72% of the patients. An LV lead was successfully placed in 95% of the patients in the CRT-D arm, and there was a 10% crossover to the CRT-D arm from the ICD arm. The main results of the RAFT study showed that the primary endpoint of all-cause mortality or hospitalisation for heart failure was significantly reduced in the CRT-D arm compared with ICD (40.3% versus 33.2%, p < 0.001). All-cause mortality was also significantly decreased (26.1% versus 20.8%, p = 0.003). This corresponded to a number needed to treat of 14 patients for 5 years to prevent one death with CRT-D compared with ICD alone. Hospitalisation for congestive heart failure was similarly reduced (26.1% versus 19.5%, p < 0.001). Results for the primary and secondary endpoints were similar for NYHA class II or III patients. Subgroup analysis showed a greater benefit with CRT-D in patients with wider QRS complex at baseline (≥150 ms for native and ≥200 ms for paced). LBBB morphology also seemed to derive greater benefit, and there was a trend towards greater efficacy in women. However, device-related hospitalisations were higher in the CRT-D arm (20.0% versus 12.2%, p < 0.001). Device- or implantation-related complications were significantly higher in the CRT-D arm, as compared with the ICD arm at 30 days (13.3% versus 6.8%, p < 0.001). The complications included haemothorax or pneumothorax, device-pocket haematomas, device-pocket infections, and lead displacement requiring intervention. The results of the RAFT study clearly indicate that in patients with NYHA class II/III (80% class II!), LV systolic dysfunction (LVEF, <30%), and a wide QRS complex, the addition of CRT to an ICD reduces all-cause mortality and hospitalisation for congestive heart failure by about 25%. On subgroup analysis, the results of the primary endpoint seemed to be more outspoken in patients with a wider QRS complex at baseline and those with LBBB morphology. There was a significant increase (twofold!) in the risk of device- or procedure-related complications at 30 days in the CRT-D arm, including a higher risk of hospitalisation for device-related causes. The higher complication rates in the RAFT trial are similar to those noted by other CRT-D trials, and careful attention to complications is therefore essential. Further studies are needed to identify optimal LV lead placement for maximal benefit and the cost-effectiveness of extending CRT-D to mildly symptomatic patients. In an accompanying editorial, Dr. Arthur Moss (Rochester, NY, USA) stated, ‘we can say that recent findings documenting the use of CRT in preventing heart failure in minimally symptomatic patients are breathtaking’ [2].

In this issue, Al-Majed and colleagues report a systematic review of 25 trials that suggests that CRT benefits patients with reduced left ventricular ejection fraction, symptoms, and prolonged QRS ...

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

As an electrophysiologist, I am referred large numbers of patients with, or at risk of, arrhythmias as part of the heart failure complex. In this review I will concentrate on the role of pacemakers and defibrillators in heart failure, because these are my areas of greatest experience. Left ventricular assist devices and implantable hemodynamic monitors will not be reviewed. The first controversy for discussion is how to assess patients for suitability to receive these devices. Patients with heart failure are frequently fitted into a New York Heart Association (NYHA) class. The NYHA class is, however, a blunt instrument for decision-making that is based on a physician's or nurse's impression of how patients express their symptoms. Two patients with similar levels of symptomatology but with different responses to their symptoms may therefore receive different NYHA classifications and be candidates for different management approaches. Guidelines such as those from the European Society of Cardiology (ESC) offer valuable guidance on the use of cardiac resynchronization therapy (CRT).12 There are, however, issues in the use of CRT which the guidelines do not consider. Controversies that relate particularly to CRT include the identification of which patients benefit most from this technique and the characterization of its role in atrial fibrillation, in patients with bradycardia, and in non-responders. CRT has been available for approximately 10 years. An early meta-analysis of randomized controlled trials of CRT, including CONTAK-CD, InSync ICD, MIRACLE, and MUSTIC, showed that CRT reduced death from progressive heart failure by 51%, reduced heart failure hospitalization by 29%, and showed a trend to reduced all-cause mortality2 (Figures 12–3). Some of these trials included a defibrillator component, which made characterization of the effects of CRT alone problematic. Subsequent to these trials, the CARE-HF study was performed. CARE-HF observed that CRT produced a 37% reduction in all-cause mortality or unplanned hospitalization compared to medical therapy over 4 years (P < 0.0001)5 (Figure 4). All-cause mortality alone was reduced 36% by CRT when compared to optimal medical therapy (P = 0.0019). CARE-HT was the first major trial to demonstrate a definite improvement in all-cause mortality from CRT pacing. The COMPANION study included patients at higher risk than those in CARE-HF and investigated three treatment limbs – optimal pharmacological therapy, biventricular pacing, and biventricular defibrillation.3 COMPANION was not powered to detect a difference in outcome between the two types of biventricular device, but did appear to show that biventricular defibrillation was superior to medical therapy based on the secondary endpoint of all-cause mortality at 12 months (Figure 5). On the basis of these trials, the ESC guidelines recommend that “CRT using biventricular pacemakers can be considered [my italics] in patients with reduced ejection fraction and ventricular asynchrony (QRS width ≥120 ms) who remain symptomatic despite optimal medical therapy (NYHA III/IV) to improve symptoms, hospitalizations, and mortality”.12 From my viewpoint, this statement may require to be updated in the revised ESC guidelines and CRT should be performed much more commonly than presently. National guidelines from the Scottish Intercollegiate Guidelines Network (SIGN), which have been more produced recently (2007) than those from the ESC (2005), make a similar statement – namely, that CRT “should be considered” in patients with characteristics similar to those described in the ESC guidelines. The English National Institute for Clinical Excellence (NICE) Health Technology Appraisal of the place of CRT in heart failure (2007) states that: “CRT with a pacing device (CRT-P) is recommended as a treatment option for patients with heart failure who fulfill the following criteria. They are currently experiencing or have recently experienced NYHA class III-IV symptoms. They are in sinus rhythm either with a QRS duration 150 ms or longer … or with a QRS duration of 120–149 ms and mechanical dyssynchrony. They have a LVEF of 35% or less. They are receiving optimal pharmacological therapy.” The NICE guidelines therefore strongly recommend CRT for a precisely defined group of patients. The NICE guidelines also offer guidance on the use of CRT with a defibrillator (CRT-D). “CRT-D may be considered for people who fulfill the criteria for implantation of a CRT-P device and who separately fulfill the criteria for use of an ICD as recommended in NICE Technology Appraisal Guidance 95.” The latter criteria include wide QRS and poor LV function post-myocardial infarction. There is controversy over whether mechanical dyssynchrony is also required for the selection of patients for CRT. Considerable heterogeneity exists in the echocardiographic criteria adopted to define dyssynchrony, but a few small observational studies suggest that echocardiographic measurement of mechanical dyssynchrony may best identify patients who are likely to benefit from CRT.7 Further work is required in this area. What are the cost implications of using CRT-P and CRT-D? Based on data from the CARE-group using data from COMPANION, the incremental cost-effectiveness of CRT-P versus medical therapy was €7538 per quality-adjusted life-year (QALY), and the incremental cost-effectiveness of CRT-D versus CRT-P was €47 909.13 CRT-P was concluded to be relatively inexpensive, while CRT-D was of borderline cost-effectiveness. The patient's age comes into consideration in deciding who, among eligible patients, should receive CRT-D. In younger patients, CRT-D may be considered affordable in order to keep patients alive for as long as possible. In patients aged above 70 years, by contrast, other factors are more likely to cause death and the cost of CRT-D compared to CRT-P becomes prohibitive. The use of CRT in patients with atrial fibrillation (AF) is a contentious issue. The ESC guidelines do not specify a rhythm, but most other guidelines do specify the presence of sinus rhythm (SR) in their recommendations. Most trials have included only patients in SR, although the MUSTIC study included approximately equal numbers of patients in SR and AF. In MUSTIC, patients in SR improved significantly, whereas those in AF did not.4,8 For patients in SR, activation of the pacemaker was associated with an improvement in 6-min walking distance, which worsened when the device was inactivated. However, it is notable that only 37 of 64 patients in AF completed both limbs of the study. A long-term follow-up of patients in MUSTIC at 9 and 12 months found that all SR patients and 88% of AF patients were programmed to biventricular pacing.9 The two groups experienced similar magnitudes of improvement in walking distance, peak VO2, quality of life, NYHA class, and ejection fraction (Figure 6). Therefore, for every factor measured, AF patients appeared to do as well as SR patients in the long term. MUSTIC and some smaller studies represent the only trial evidence on which to base treatment in patients with AF. This raises the question of whether the potential benefits of CRT should be denied to AF patients in the absence of large-scale randomized studies. Opinions obtained from members of the Heart Rhythm UK suggest that most large centers are implanting CRT devices in a proportion of AF patients. There are two schools of thought on the type of AF patient who may benefit from CRT. In one school, CRT should be offered to the relatively small numbers of patients in whom rigorous rate control can be achieved by medical therapy and, if necessary, ablation of atrioventricular conduction to ensure biventricular pacing all of the time. According to the results of MUSTIC, this group may improve. This is called the “rate control” group. In the second school of thought, patients should be selected in whom stringent efforts will be made to restore and maintain SR. CRT may help by increasing the ejection fraction, lowering mitral regurgitation, and lowering left ventricular pressure. Cardioversion will be easier, and amiodarone and atrial catheter ablation may be added. This is called the “rhythm control” group. It is clear that the rate control group and the rhythm control groups encompass almost all patients with AF who fit CRT criteria. In other words, there is little agreement on which patients not to implant. Another controversial area is that, in every trial, there are patients classified as “non-responders”, who represent approximately 40% of the study population. In a proportion of these cases, however, the CRT device is stabilizing the patient who would otherwise deteriorate. Although the patient may complain of not feeling better, the device may actually be preventing deterioration or death. This situation illustrates the difficulty in measuring response. Other indices may need to be assessed, such brain natriuretic peptide levels, echocardiography/magnetic resonance imaging, and evidence of dyssynchrony, in order to identify patients who will benefit from CRT. CRT-D is an option in younger patients, especially those considered for future transplantation, while CRT-P may be provided in older patients to improve symptoms and reduce hospitalization. CRT-D may be considered in the presence of risk factors for sudden death, such as non-sustained ventricular tachycardia (VT) or T-wave alternans. The role of CRT-D in Class IV heart failure and AF requires clarification. Controversies that relate particularly to the use of implantable cardioverters-defibrillators (ICDs) include the identification of which patients will benefit from an ICD or from a CRT plus an ICD, whether the trial evidence for coronary artery disease can be extrapolated to dilated cardiomyopathy (DCM), and issues of deactivation at end of life. The ESC guidelines state that: “Implantation of an ICD in combination with biventricular pacing can be considered (my italics) in patients who remain symptomatic with severe heart failure (NYHA class III/IV) with LVEF [left ventricular ejection fraction] ≤35% and QRS duration >120 ms to improve morbidity or mortality”. “ICD therapy is recommended (my italics) to improve survival in patients who have survived cardiac arrest or who have sustained VT, which is either poorly tolerated or associated with reduced systolic LV function.” “ICD implantation is reasonable (my italics) in selected symptomatic patients with LVEF <30–35%, not within 40 days of a myocardial infarction, on optimal background therapy … to reduce sudden death.” The largest trial that has provided evidence to substantiate these statements is SCD-HeFT.1 SCD-HeFT randomized 2500 patients with symptomatic heart failure (NYHA II/III) and LVEF <35% to no antiarrhythmic therapy, amiodarone, or ICD with a 5-year follow-up. One half of the patients had an ischaemic etiology and one half had idiopathic DCM. Patients were relatively young (mean 60 years) and a proportion were overweight (mean 85 kg). Background medication use with an ACE inhibitor or angiotensin receptor blocker and beta-blocker was good, with rates approaching 90% and 80%, respectively, and use of spironolactone (31% at last follow-up) was reasonable. Loop diuretics were prescribed in the majority. Annual mortality over 5 years was 7.2% in the placebo group. Amiodarone had no influence on morality (hazard ratio [HR] 1.06. P = 0.529 vs placebo), but ICD significantly reduced the mortality rate (HR 0.77, P = 0.007 vs placebo) (Figure 7). Analysis of subgroups showed that the HR of mortality for ICD versus placebo was 0.54 in patients with NYHA II and 1.16 in those with NYHA class III, indicating that patients with Class II heart failure benefited while those with Class III tended to fare worse. Patients with an ischaemic or non-ischaemic etiology had HRs of 0.79 and 0.73, respectively, suggesting equal benefit from ICD. Further subgroup analyses indicated that patients with a low EF (≤30%) had the most to gain (HR 0.73, vs 1.08 for those with an EF >30%), as did those on beta-blocker therapy (HR 0.68, vs 0.92 for those not on beta-blocker therapy), which emphasizes that ICD therapy is not a substitute for good medical therapy. There have been problems in interpreting the outcomes of studies such as SCD-HeFT and MADIT-II.10 The reliance on subgroup analyses in these trials has reduced the power of these studies. Inaccuracies in measurement utilizing LVEF cutoff values and NYHA class has further hampered interpretation, and the relationship between the severity of the condition and the magnitude of improvement requires clarification. No “evidence base” exists on which to guide practice at end of life. Discussing these issues with the patient and relatives is difficult, but needs to be done openly and with sensitivity if any crisis or deterioration develops. Booklets and websites are a valuable source of information that patients can choose to look at, and base decisions on, at their own pace. In the UK, information for patients on websites is available from the British Heart Foundation (www.bhf.org) and the Arrhythmia Alliance (www.arrhythmiaalliance.org.uk). Primary prevention ICDs may be considered in stable heart failure patients who are already receiving optimal medical therapy. ICD should not be considered as a substitute for medical therapy. Ischaemic and non-ischaemic patients benefit equally from ICD, and the worse the LV function, the greater is the benefit. ICD may be considered as a bridge to transplant or, alternatively, as a means to keep the patient away from transplant.

Developed in Collaboration With the American Association for Thoracic Surgery, Heart Failure Society of America, and Society of Thoracic Surgeons

POSTER PRESENTATIONS

Contemporary and future trends in cardiac resynchronization therapy to enhance response

ORAL PRESENTATION

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 …

Managing atrial fibrillation in the CRT patient: Controversy or consensus?

There is evidence that implantable cardioverter-defibrillator (ICD) for primary prevention in people with an ischaemic cardiomyopathy improves survival rate. The evidence supporting this intervention in people with non-ischaemic cardiomyopathy is not as definitive, with the recently published DANISH trial finding no improvement in survival rate. A systematic review of all eligible studies was needed to evaluate the benefits and harms of using ICDs for primary prevention in people with non-ischaemic cardiomyopathy. To evaluate the benefits and harms of using compared to not using ICD for primary prevention in people with non-ischaemic cardiomyopathy receiving optimal medical therapy. We searched CENTRAL, MEDLINE, Embase, and the Web of Science Core Collection on 10 October 2018. For ongoing or unpublished clinical trials, we searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the ISRCTN registry. To identify economic evaluation studies, we conducted a separate search to 31 March 2015 of the NHS Economic Evaluation Database, and from March 2015 to October 2018 on MEDLINE and Embase. We included randomised controlled trials involving adults with chronic non-ischaemic cardiomyopathy due to a left ventricular systolic dysfunction with an ejection fraction of 35% or less (New York Heart Association (NYHA) type I-IV). Participants in the intervention arm should have received ICD in addition to optimal medical therapy, while those in the control arm received optimal medical therapy alone. We included studies with cardiac resynchronisation therapy when it was appropriately balanced in the experimental and control groups. The primary outcomes were all-cause mortality, cardiovascular mortality, sudden cardiac death, and adverse events associated with the intervention. The secondary outcomes were non-cardiovascular death, health-related quality of life, hospitalisation for heart failure, first ICD-related hospitalisation, and cost. We abstracted the log (hazard ratio) and its variance from trial reports for time-to-event survival data. We extracted the raw data necessary to calculate the risk ratio. We summarised data on quality of life and cost-effectiveness narratively. We assessed the certainty of evidence for all outcomes using GRADE. We identified six eligible randomised trials with a total of 3128 participants. The use of ICD plus optimal medical therapy versus optimal medical therapy alone decreases the risk of all-cause mortality (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.66 to 0.92; participants = 3128; studies = 6; high-certainty evidence). An average of 24 patients need to be treated with ICD to prevent one additional death from any cause (number needed to treat for an additional beneficial outcome (NNTB) = 24). Individuals younger than 65 derive more benefit than individuals older than 65 (HR 0.51, 95% CI 0.29 to 0.91; participants = 348; studies = 1) (NNTB = 10). When added to medical therapy, ICDs probably decrease cardiovascular mortality compared to not adding them (risk ratio (RR) 0.75, 95% CI 0.46 to 1.21; participants = 1781; studies = 4; moderate-certainty evidence) (possibility of both plausible benefit and no effect). Implantable cardioverter-defibrillator was also found to decrease sudden cardiac deaths (HR 0.45, 95% CI 0.29 to 0.70; participants = 1677; studies = 3; high-certainty evidence). An average of 25 patients need to be treated with an ICD to prevent one additional sudden cardiac death (NNTB = 25). We found that ICDs probably increase adverse events (possibility of both plausible harm and benefit), but likely have little or no effect on non-cardiovascular mortality (RR 1.17, 95% CI 0.81 to 1.68; participants = 1781; studies = 4; moderate-certainty evidence) (possibility of both plausible benefit and no effect). Finally, using ICD therapy probably has little or no effect on quality of life, however shocks from the device cause a deterioration in quality of life. No study reported the outcome of first ICD-related hospitalisations. The use of ICD in addition to medical therapy in people with non-ischaemic cardiomyopathy decreases all-cause mortality and sudden cardiac deaths and probably decreases mortality from cardiovascular causes compared to medical therapy alone. Their use probably increases the risk for adverse events. However, these devices come at a high cost, and shocks from ICDs cause a deterioration in quality of life.

Sudden cardiac death (SCD) is a major public health problem in North America, responsible for approximately 400 000 deaths annually.1,2 Most episodes of SCD in ambulatory populations result from ventricular tachyarrhythmias,3 whereas bradyarrhythmias may be important in some populations, notably hospitalized patients with advanced heart failure4 (Figure 1). A prior article in this series by Zipes and Wellens2 provides a detailed review of the pathogenesis of SCD, its underlying causes, and treatment strategies. Figure 1. Mechanisms of SCD in ambulatory persons. Most SCDs result from ventricular fibrillation. VT, bradyarrhythmias, and other mechanisms account for the remainder. ### ICD Therapy The availability of a therapy that reliably terminates the vast majority of life-threatening tachyarrhythmic and bradyarrhythmic events has tremendous clinical appeal. The implantable cardioverter defibrillator (ICD) represents such a therapy. Despite its appeal, the ICD is imperfect. Currently, systems are costly, have a limited life expectancy, and are subject to complications in the long term.5,6 Furthermore, many patients at risk for SCD are at risk of dying from causes that the ICD would not alter. The impact of ICD shocks also merits consideration. Evidence links multiple shocks with myocardial injury7 and fibrosis,8 and sporadic shocks are associated with significant, independent reductions in quality of life. Compared with patients not having shocks, patients in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial who had ≥1 shocks in the initial year of follow-up had significant declines in self-perceived physical functioning and mental well-being, independent of ejection fraction (EF), social circumstances, and medication use. The reduction in quality of life associated with shocks was of a magnitude similar to clinically important adverse effects from amiodarone.9 Cost-efficacy is a vital issue in settings of limited or restricted health care resources6 and is particularly relevant as ICD use is expanded to …

His-bundle pacing is the best approach to physiological pacing.

Can we predict, prevent, and minimize defibrillator shocks? Lessons learned from “remote monitoring”