Temporal Trends and Outcomes of Implantable Cardioverter Defibrillators in Heart Failure and Chronic Kidney Disease in the United States

Chronic kidney disease (CKD) and hemodialysis increase the risk of sudden cardiac death (SCD) in heart failure (HF); however, national trends in utilization and outcomes of implantable cardioverter-defibrillator (ICD) in this population remain unknown. We sought to evaluate the utilization and outcomes of ICD therapy in HF patients with CKD and end-stage renal disease (ESRD) using the National Inpatient Sample from 2009 to 2018. Hospitalizations with a discharge diagnosis of systolic HF and ICD implantation were identified and stratified by stages of kidney disease. A total of 281,219 systolic HF hospitalizations who underwent ICD implantation were included. A significant decrease in inpatient ICD implantation was observed over the past decade (3.7% in 2009 to 1.1% in 2018) regardless of renal impairment. In-hospital mortality was highest in ESRD, followed by CKD compared with patients with no CKD. Length of hospital stay and hospitalization costs were also significantly higher in patients with CKD and ESRD. The overall utilization of inpatient ICD implantation has decreased in systolic HF patients and inpatient ICD placement in CKD is associated with an increased risk of mortality and adverse clinical outcomes. This indicates that patients with renal impairment and HF represent a sicker cohort than the general HF population.     

Electrical manipulation of the failing heart

Chronic heart failure with reduced (≤?40%) ejection fraction (HFrEF) poses a significant residual mortality risk despite modern optimal medical therapy. In the last decades, we have witnessed the introduction of breakthrough cardiac implantable electronic devices (CIED) aimed at addressing sudden cardiac death and HF progression in patients with HFrEF, leading to improved survival and functional capacity. Following their introduction, implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) have undergone substantial technological improvements and have been investigated in different settings of HFrEF, some of which yielded controversial results. In this review, we provide a comprehensive, yet pragmatic, approach to the individual key points in the electrical manipulation of the failing heart with ICD and CRT including patient selection, technological advances in the implant technique, follow-up, and long-term management. The aim of the review is to provide real-life-oriented advices to maximize the desired outcomes of CIED-based therapy of HFrEF. Accordingly, a framework to inform the decision-making process in candidates to ICD and/or CRT has been developed reflective of a critical appraisal of the most recently available evidence reappraising some domains beyond the classic views.     

Sudden death prophylaxis in heart failure

Sudden cardiac death (SCD) is the leading cause of mortality in heart failure (HF). Today the implantable cardioverter-defibrillator (ICD) has become a commonplace therapy around the world for patients with both ischemic and non-ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF alone does not discriminate between the modes of death from HF (sudden arrhythmic death vs. non-sudden death). Other risk statifiers, such as electrophysiologic study and microvolt T-wave alternans testing, should therefore be used in the appropriate settings to minimize the number of unnecessary device implants. In addition, left ventricular mechanical dyssynchrony has now become recognized as an additional major marker of cardiac mortality. Its assessment should entail echocardiography rather than measurement of the QRS duration. This will allow us to better integrate the ability of cardiac resynchronization therapy (CRT) in enhancing cardiac function with the ability of an ICD in preventing SCD. This review aims to: 1) give a synthesis of the published evidence regarding the value of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss controversial clinical issues in this area; and 3) recommend practical device-based management strategies.     

Electrical devices for left ventricular dysfunction and heart failure: do we need revised guidelines?

Three recent trials have demonstrated the benefit of cardiac resynchronization therapy (CRT) in the New York Heart Association (NYHA) class II patients with heart failure (HF) with ischemic or nonischemic cardiomyopathy as well as in NYHA class I (asymptomatic) patients mostly with ischemic cardiomyopathy. Earlier intervention with CRT in asymptomatic or minimally symptomatic patients improves survival and reduces HF hospitalizations. The reduction or the prevention of HF hospitalizations is of paramount importance because the HF episodes seem to alter the natural history of disease and are associated with deterioration of left ventricular (LV) function and a marked increase in mortality. The CRT benefit is greatest in patients with a QRS ≥ 150 ms. At this time, it would seem prudent to consider CRT-D (D = ICD) therapy for class I NYHA patients with a QRS ≥ 150 ms and an LV ejection fraction ≤ 30% regardless of etiology. Although the data for NYHA class I patients with nonischemic cardiomyopathy are scanty, the recommendation for class I patients is justified because CRT achieves a much greater degree of LV reverse remodeling in nonischemic compared to ischemic patients. With regard to lone ICDs, there is no evidence that they prevent sudden cardiac death more efficiently in symptomatic than in asymptomatic patients. Cardiomyopathy should be the primary target for device therapy regardless of symptoms for both CRT and lone ICD therapy. New guidelines are needed to address the role of CRT in hospitalized NYHA class IV HF patients or those who depend on inotropic therapy or an LV assist device because randomized CRT trials have not included these patients. CRT in these patients remains controversial. The mortality of such patients even with CRT is very high despite the occasional positive response. The role of CRT in patients waiting for cardiac transplantation also needs guidelines. With the expansion of CRT indications to minimally symptomatic or asymptomatic patients, the benefit of device therapy must be carefully weighed against the potential risk of lifelong device complications.     

Current role of device therapy to reduce sudden cardiac death in heart failure

Sudden cardiac death (SCD) continues to be a major contributor to mortality in patients with heart failure (HF) despite recent advances in medical therapy. Device therapy, including the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT), serves as an adjunct in reducing HF mortality. Several clinical trials support the prophylactic use of the ICD in reducing mortality in certain HF populations and have established the clinical benefits of CRT in advanced HF. More recently, the Comparison of Medical Therapy Pacing and Defibrillation in Heart Failure trial was the first study to demonstrate a survival benefit of CRT alone or in conjunction with an ICD. This article reviews the most pertinent data regarding the role of device therapy in reducing SCD in HF and addresses future challenges faced by device manufacturers and clinicians.     

Long-term survival of patients with heart failure and ventricular conduction delay treated with cardiac resynchronization therapy

This multicenter longitudinal observational trial was designed to analyze the long-term outcome of patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) alone or with implantable cardioverter-defibrillator (ICD) backup in a daily practice scenario. It is unknown whether the magnitude of survival benefits conferred by CRT in a daily practice scenario is comparable to what has been observed in randomized controlled trials and whether this benefit is sustained over the long term. The outcome of 1,303 consecutive patients with ischemic or nonischemic cardiomyopathy on optimal pharmacologic therapy treated from August 1, 1995 to August 1, 2004 at 4 European centers with CRT alone (44%) or with ICD backup for symptomatic HF and prolonged QRS duration was assessed. Cumulative event-free survival was evaluated for a combined end point, defined as death from any cause, urgent transplantation, or implantation of a left ventricular assist device. The cumulative incidence of competing events, HF, sudden cardiac death, and noncardiac death, was also assessed. Event-free survival was similar across the different centers. At 1 and 5 years, cumulative event-free survivals were 92% (95% confidence interval [CI] 91 to 94) and 56% (95% CI 48 to 64), respectively. The cumulative incidence of HF deaths was 25.1% (95% CI 19 to 31.7), whereas that of sudden death was 9.5% (95% CI 5.1 to 15.7). Using multivariate analysis, CRT with an ICD backup was associated with a nonsignificant decrease in mortality by 20% (hazard ratio 0.83, 95% CI 0.58 to 1.17, p = 0.284), with a highly significant protective effect against sudden cardiac death (hazard ratio 0.04, 95% CI 0.04 to 0.28, p <0.002). In conclusion, patients with advanced HF and a wide QRS complex routinely treated with CRT have a favorable long-term outcome that was reproducible at different centers. The leading cause of death in these patients remained HF, and this mode of death was competing with other causes in determining outcome. Total mortality was 20% lower with ICD backup (95% CI 42% lower to 17% higher) due to a protective effect against sudden cardiac death.     

The future of implantable defibrillator and cardiac resynchronization therapy trials

Implantable cardioverter defibrillator (ICD) trials were initially limited to survivors of sudden death. The focus of defibrillator trials in the last decade has been in prophylactic implantation of the device in high risk populations for the prevention of sudden cardiac death. It is the contention in this review that the new focus for implantable defibrillator trials in 2008 and beyond will be on more selective and focused use of this therapy. This could be achieved by selecting ICD patients based on their pathophysiologic and genetic risk. Increasing effort will also be placed on using the device for prevention of spontaneous malignant ventricular tachyarrhythmias and the index clinical sudden death event. Finally, implantable defibrillators will be used in combination in a “hybrid” therapy approach. ICDs will be increasingly combined either with ventricular tachycardia ablation or ventricular fibrillation ablation using catheter techniques. With the addition of cardiac resynchronization therapy in these devices, new clinical trials that use cardiac resynchronization therapy as an early intervention in specific high risk heart failure populations and refinement of the CRT technique to improved optimal results are in progress. Finally, combining ICD devices and regenerative medicine approaches to myocardial replacement therapy are being explored. Dr. Saksena is a consultant and/or investigator for Medtronic Inc., St. Jude Medical Inc., Sanofi Aventis, and Aryx Pharmaceuticals.     

Sex-based differences in cardiac resynchronization therapy and implantable cardioverter defibrillator therapies: effectiveness and use

With the rapid advancements in heart failure device therapy, many physicians now use these devices in everyday clinical practice. However, questions remain regarding the clinical benefit of these therapies in different patient subgroups. Since the majority of patients enrolled in device trials are white men, extrapolating the data to specific patient subpopulations becomes important. Specifically, the question of clinical outcomes in women with implantable device therapy for prevention of sudden cardiac death and management of heart failure is an important clinical issue. In this article, we review the data on survival and clinical outcomes with heart failure device therapy (implantable cardioverter defibrillators [ICDs] and cardiac resynchronization therapy [CRT]) and analyze the results from clinical trials for any differences in outcomes based on gender. Even though women are a significantly under-represented population with regard to clinical investigation and utilization of heart failure devices, they still derive the same morbidity and mortality benefits compared to men. Specifically, ICD devices confer the same rates of sudden cardiac death prevention, and CRT devices improve CHF morbidity and mortality at rates comparable to those found in men. These results support equal use of ICDs and CRT in men and women.     

Benefit of primary prevention implantable cardioverter-defibrillators in the setting of chronic kidney disease: a decision model analysis

Introduction: Primary prevention ICD trials have excluded patients with CKD. Comorbidities and lower life expectancy in patients with CKD make the benefit of primary prevention ICD implantation uncertain. Methods: A decision analysis model was devised to evaluate the risks and benefits of implantable cardioverter‐defibrillators (ICD) implantation in patients with chronic kidney disease (CKD) who meet current criteria for a primary prevention ICD. Published data capturing event rates, infection risks, and overall survival in CKD patients with and without ICDs were utilized. Variables included patient's age, GFR and stage of CKD, probability of sudden cardiac death (SCD), and device implantation mortality. Results: The benefit of an ICD for primary prevention of SCD in patients with CKD depends primarily on the patient's age and stage of kidney disease. With stages 1 and 2 CKD, ICD implantation reduces mortality. However, in patients with more advanced stages of CKD, the benefit is less significant and age‐dependent. This is attributed to patients with advanced CKD having a higher procedural risk and decreased life expectancy. With average procedural mortality, ICD implantation is favored at ages <80 for stage 3, ages <75 for stage 4, and ages <65 for stage 5. As procedural mortality rates increase, age thresholds for ICD implantation decrease. Conclusions: Our model shows that benefit from primary prevention ICD implantation is determined by the patient's age and stage of kidney disease. While there is limited impact with lower stages of CKD, careful consideration of ICD implantation is suggested for older patients with more advanced stages of kidney disease.     

Implantable device therapy

Sudden cardiac death (SCD) accounts for two-thirds of fatal events related to heart disease. Coronary heart disease and non-ischemic cardiomyopathy are the most common causes of SCD. Data from major randomized trials have consistently shown that therapy with an implantable cardioverter defibrillator (ICD) results in a significant and meaningful effect on survival through a reduction in the risk of SCD in these population. These data have resulted in a marked increase in the application of implantable device therapy in the past 2 decades from secondary prevention with an implantable cardioverter/defibrillator (ICD) in survivors of a cardiac arrest to primary prevention of SCD in asymptomatic patients with ischemic and non-ischemic left ventricular dysfunction, and prevention of symptomatic heart failure progression and death with cardiac resynchronization therapy (CRT), and devices that combine CRT and ICD therapies (CRT-D). However, there are still areas of uncertainty regarding device therapy that include inconsistent benefit in risk-subgroups of patients with low ejection fraction; increased risk of heart failure after life-prolonging ICD therapy, and a considerable rate of device malfunction despite increasing sophistication. In the present review we focus on current data regarding the clinical indications as well as the safety and efficacy of implantable device therapy, including ICD, CRT, and CRT-D.     

Roles and indications for use of implantable defibrillator and resynchronization therapy in the prevention of sudden cardiac death in heart failure

Implantable devices are indicated in the primary and secondary prevention of potentially life-threatening ventricular tachyarrhythmias in patients with heart failure. Early studies, including the landmark MADIT trials, showed that implantable cardioverter–defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices can play a significant role in aborting and preventing ventricular arrhythmias, respectively, that can cause sudden cardiac death. To this day, there have been a number of randomized controlled trials, with respective substudy analyses, that have attempted to better understand the indications for these interventions in patient care. Here, we summarize the major results of these studies, and we discuss the role of ICD therapy for both ischemic and non-ischemic cardiomyopathy, emerging evidence in support of wearable defibrillators, and the impact of modified ICD programming strategies on patient outcomes. Regarding CRT therapy, the phenomenon of ventricular reverse remodeling is an important prognostic indicator in preventing future ventricular tachyarrhythmia episodes. In summation, we provide an overview of the possible selection criteria that can be used in identifying appropriate patients for ICD and/or CRT therapy, as supported by the data.     

Influence of cardiac-resynchronization therapy on heart rate and blood pressure variability: 1-year follow-up

BACKGROUND: Several studies have shown that cardiac-resynchronization therapy (CRT) improves haemodynamic function, cardiac symptoms, and heart rate variability (HRV) and reduces the risk of mortality and sudden death in subjects with chronic heart failure (CHF). In subjects with CHF, power spectral values for the low-frequency (LF) component of RR variability < or =13 ms2, are associated with an increased risk of sudden death. AIMS AND METHODS: To assess whether spectral indexes obtained by power spectral analysis of HRV and systolic blood pressure (SBP) variability could predict malignant ventricular arrhythmias in patients with severe CHF treated with an implantable cardioverter-defibrillator (ICD) alone or with ICD+CRT. In addition, changes in non-invasive spectral indices using short-term power spectral analysis of HRV and SBP variability during controlled breathing in 15 patients with CHF treated with an ICD alone and 16 patients receiving ICD+CRT, were assessed pre-treatment and at 1 year. RESULTS: Arrhythmias necessitating an appropriate ICD shock were more frequent in subjects who had low LF power. CRT improved all spectral components, including LF power. CONCLUSIONS: Low LF power values predict an increased risk of malignant ventricular arrhythmias; after 1 year of CRT most non-spectral and spectral data, including LF power, improved. Whether these improvements lead to better long-term survival in patients with CHF remains unclear.     

Current status of implantable cardioverter-defibrillator therapy in heart failure

Sudden cardiac arrest is one of the leading causes of death in patients with heart failure (HF). The implantable cardioverter-defibrillator (ICD) is the only evidence-based treatment strategy for patients who have survived a life-threatening ventricular arrhythmic event. Randomized clinical trials have shown that specific subsets of HF patients with ischemic and nonischemic dilated cardiomyopathy benefit from ICD therapy for primary prevention of sudden cardiac arrest. Cardiac resynchronization therapy has become the device-based therapy of choice for improving symptoms and survival in severe HF patients with evidence of ventricular dyssynchrony. This review summarizes the current status of ICD therapy in treating HF patients based on randomized clinical trials and current practice guidelines.     

Effect of risk stratification on cost-effectiveness of the implantable cardioverter defibrillator

Background Implantable cardioverter defibrillators (ICDs) effectively prevent sudden cardiac death, but selection of appropriate patients for implantation is complex. We evaluated whether risk stratification based on risk of sudden cardiac death alone was sufficient to predict the effectiveness and cost-effectiveness of the ICD. Methods We developed a Markov model to evaluate the cost-effectiveness of ICD implantation compared with empiric amiodarone treatment. The model incorporated mortality rates from sudden and nonsudden cardiac death, noncardiac death and costs for each treatment strategy. We based our model inputs on data from randomized clinical trials, registries, and meta-analyses. We assumed that the ICD reduced total mortality rates by 25%, relative to use of amiodarone. Results The relationship between cost-effectiveness of the ICD and the total annual cardiac mortality rate is U-shaped; cost-effectiveness becomes unfavorable at both low and high total cardiac mortality rates. If the annual total cardiac mortality rate is 12%, the cost-effectiveness of the ICD varies from $36,000 per quality-adjusted life-year (QALY) gained when the ratio of sudden cardiac death to nonsudden cardiac death is 4 to $116,000 per QALY gained when the ratio is 0.25. Conclusions The cost-effectiveness of ICD use relative to amiodarone depends on total cardiac mortality rates as well as the ratio of sudden to nonsudden cardiac death. Studies of candidate diagnostic tests for risk stratification should distinguish patients who die suddenly from those who die nonsuddenly, not just patients who die suddenly from those who live. (Am Heart J 2002;144:440-8.)     

Update on implantable cardioverter defibrillator trials

Many randomized trials of implantable cardioverter defibrillator (ICD) therapy versus medical treatment for the prevention of death in survivors of cardiac arrest or in patients at high risk of sudden cardiac death (SCD) have been reported. ICD therapy has been consistently efficacious in preventing SCD. ICD therapy has generally favorably impacted total mortality, but this has depended upon the control group's risk for arrhythmic and nonarrhythmic mortality. In these trials, predictors of sudden or total mortality better than ventricular dysfunction have not emerged. This review summarizes the randomized ICDs trials and the impact ICDs have on SCD prevention.     

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.     

Outcomes of ICDs and CRTs in patients with chronic kidney disease: a meta-analysis of 21,000 patients

Purpose

The efficacy of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) in patients with chronic kidney disease (CKD) remains unclear. The aim of this meta-analysis is to explore the association between ICD/CRT and mortality in CKD patients.

Methods

An electronic search was conducted using MEDLINE. We included studies that reported outcomes of interest in CKD patients stratified by the presence of ICD, CRT, or none. The primary outcome was all-cause mortality. Outcomes were pooled using random effects model. Odds ratios (OR) were reported for dichotomous variables.

Results

The literature search resulted in 11 studies (observational studies) including 21,136 adult patients: seven studies compared ICD vs. no ICD and four studies compared CRT vs. ICD. All-cause mortality was significantly lower in the ICD group in comparison to that in the no ICD group (OR 0.66 (95% confidence interval [CI] 0.45; 0.98), P?=?0.04). Among dialysis-only patients, all-cause mortality was significantly lower in the ICD group (OR 0.49 (95% CI 0.38; 0.64), P?<?0.001). All-cause mortality was significantly lower in the CRT group in comparison to that in the ICD group (OR 0.73 (95% CI 0.57; 0.92), P?=?0.01).

Conclusions

The use of ICDs is associated with lower all-cause mortality in observational studies of CKD patients. CRT use was also associated with lower all-cause mortality in CKD patients in comparison to ICDs. A randomized controlled trial is required to definitively define the role of ICDs/CRTs in CKD patients.

     

Is implantable defibrillator indicated in all patients on cardiac resynchronization therapy?

Implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have been introduced during the recent years to improve survival, decrease hospital readmissions and mortality, and to improve functional status and quality of life for patients with heart failure and left ventricular systolic dysfunction (LVSD). Studies which evaluated the use of CRT or ICD alone or compared CRT with CRT-ICD in patients with heart failure and LVSD are listed in this article. The results obtained are already influencing clinical practice in the US, where it has been estimated that 90% of patients receiving a CRT device now are being implanted with an ICD component. However, it is still today debated whether patients with LVSD and heart failure should be routinely offered a CRT-ICD. In fact, there are some issues that still should be solved before to establish indication for CRT-D in all heart failure patients with an indication for CRT: 1) a non complete agreement among the different societies which wrote recommendations for guidelines (a comparative table is reported); 2) a better identification of implantable patients and an amelioration of utilized devices; 3) economic and ethical ramifications of this therapy. Anyway still now the crucial question is: 'Can resynchronization be done in isolation or must be accompanied by an ICD device?'. To answer to this question we can only express which is, in our opinion, the actual position of many physicians who work in the field of pacing and electrophysiology: 'The lesson to be learned is that we still can not predict surely which patient will die of sudden death. Until a method of identifying the high risk patients can be developed, the safest strategy should be to advise a combined ICD-CRT device for patients with indication for CRT'.     

The current role of cardiac resynchronization therapy in reducing mortality and hospitalization in heart failure patients: a meta-analysis from clinical trials

Many diagnostic and therapeutic advances have been reached for congestive heart failure (HF). However, despite clinical improvement and longer survival conferred by new pharmacological options, this syndrome is associated with high morbidity and mortality. Atrial-synchronized biventricular pacing (cardiac resynchronization therapy, CRT) has proven to be effective treatment in symptomatic patients with reduced left ventricular ejection fraction and electromechanical dyssynchrony. To date, many papers have been published on the role of CRT in improving quality of life, functional and neurohormonal parameters and reducing mortality and hospitalization. Eligible studies were randomized controlled trials of CRT for the treatment of chronic, symptomatic left ventricular dysfunction. Our search began dating back to 1994 and was updated to October 2006. Pooled data from the 6 selected studies showed that CRT reduced all-cause mortality by 28% (hazard ration [HR] = 0.72; 95% confidence interval [CI]: 0.60-0.86) and new hospitalizations for worsening HF by 37% (HR = 0.63; 95% CI: 0.44-0.91). This meta-analysis showed that patients with implantable cardiac defibrillators (ICDs) alone and ICD+CRT had a significant reduction of worsening HF hospitalization rate compared to no CRT-no ICD patients. Among patients with ICDs, CRT showed a slight effect on all-cause mortality reduction but no clear impact on worsening HF rehospitalization.     

Outcomes of elderly heart failure recipients of ICD and CRT

Implantable cardioverter defibrillator (ICD) therapy has been established as a highly effective method for primary and secondary prevention of sudden cardiac death in heart failure patients. In addition, cardiac resynchronization therapy (CRT) with and without defibrillator back-up improves symptoms, exercise capacity and prognosis in selected patients with advanced heart failure and intraventricular conduction delay. Unfortunately, mean patient age in ICD- and CRT-intervention trials was only 60 to 65 years with few patients being older than 75 years. None of these trials separately studied an elderly heart failure population. This review summarizes the available scientific evidence for the use of ICDs and CRT devices in elderly heart failure patients based on subgroup analyses of prospective randomized ICD- and CRT-intervention trials, and based on published cohort studies.