Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure
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Abstract
Background:
The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation.
Methods:
All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of χ2 analysis.
Results:
Median age of the study population was 63 years (range, 21–84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003–1.06; P=0.03). An optimal age cutoff for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and ICD in patients ≤70 years of age (HR, 0.70; 95% CI, 0.51–0.96; P=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68–1.62; P=0.84). For patients ≤70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3–2.5) and nonsudden death rate was 2.7 (95% CI, 2.1–3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8–3.2) and nonsudden death rate was 5.4 (95% CI, 3.7–7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant (P=0.01).
Conclusions:
In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ≤70 years yielded the highest survival for the population as a whole.
Clinical Trial Registration:
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.
Introduction
Editorial, see p 1781
Clinical Perspective
What Is New?
In the present study, we explored further the association between implantable cardioverter-defibrillator (ICD) and all-cause mortality by age in the DANISH study (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality). We found a mortality reduction in association with an ICD in the younger part of the population only, and data from this study suggest an age cutoff of 70 years.
Modes of death differ according to age, and younger patients more often experience sudden cardiac death, which is why an ICD was found to be associated with improved survival rates.
What Are the Clinical Implications?
ICDs were associated with reduced all-cause mortality only in the younger part of the population of patients with nonischemic systolic heart failure.
Younger patients seem to benefit more from an ICD than older patients, primarily because sudden cardiac death accounts for a higher proportion of death in the younger patients.
Patients with systolic heart failure are at increased risk of sudden cardiac death (SCD).1 An implantable cardioverter-defibrillator (ICD) significantly reduces this risk in patients with systolic heart failure caused by ischemic heart disease.2 However, no single study based exclusively on patients with systolic heart failure not caused by coronary artery disease has demonstrated a mortality reduction with ICD implantation. The recent DANISH study (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality) found no reduction in all-cause mortality when patients with nonischemic systolic heart failure were treated with an ICD.3 However, the association of ICD implantation with survival was significantly different depending on age, with lower all-cause mortality in the 2 youngest tertiles combined but not in the older tertile. Although a possible age-dependent relationship of ICDs with survival is a relevant clinical question, few data on this exist.
The majority of deaths in patients with chronic systolic heart failure result from cardiovascular causes, mainly fatal arrhythmias or worsening of heart failure, but a substantial number of patients also die of noncardiovascular causes.4 An ICD can prevent SCD caused only by ventricular tachyarrhythmia, severe bradycardia, or complete heart block; it cannot provide protection against other causes of death.5 The causes of death in patients with heart failure change with age.6 Younger patients may be more prone to ventricular tachyarrhythmia, whereas older patients may be more likely to die of pump failure or noncardiovascular reasons.4
The purpose of the present analysis is to provide further insight into the relationship between ICD implantation and all-cause mortality and SCD by age.
Methods
The DANISH Study
The detailed design of the DANISH trial was reported previously.7 In brief, DANISH was a randomized controlled trial addressing ICD implantation in patients with nonischemic systolic heart failure.3 In total, 1116 patients with documented nonischemic systolic heart failure with left ventricular ejection fraction ≤35% and increased levels (>200 pg/mL) of NT-proBNP (N-terminal pro–brain natriuretic peptide) were randomized to ICD or control. Exclusion of ischemic heart disease as the cause of heart failure was done by coronary angiography (96% of patients), computed tomography angiography, or nuclear myocardial perfusion imaging. Patients were primarily in New York Heart Association functional class II or III. New York Heart Association class IV was accepted in candidates for cardiac resynchronization therapy (CRT). Patients with preexisting conventional pacemaker or CRT-pacemaker could be included. Patients with permanent atrial fibrillation and a resting heart rate >100 bpm and patients with end-stage renal failure (dialysis) were excluded.
Ethics
The study was performed according to the principles of the Declaration of Helsinki. Patients were enrolled only after providing informed consent. The study was approved by the regional scientific ethics committee for the capital region (H-D-2007-0101) and the Danish Data Protection Agency. In addition, the trial is registered at ClinicalTrials.gov with the identifier NCT00542945.
Age Groups and Causes of Death
Age was the only prespecified subgroup with a significant treatment-by-subgroup interaction in the DANISH trial (P=0.009 for interaction with age divided into tertiles). Age tertiles based on age at randomization were used for initial demographic analysis according to the prespecified analysis plan: age group 1, <59 years; age group 2, 59 to <68 years; and age group 3, ≥68 years.
The primary end point, death resulting from any cause, and the secondary end points of cardiovascular death, SCD, and noncardiac death were adjudicated according to previously reported criteria by a clinical end-point committee.7 Cardiovascular deaths were subclassified as sudden or nonsudden. SCD was defined as death occurring unexpectedly in a previously stable patient, death occurring within an hour of onset or worsening of symptoms, or unwitnessed death, when patients were last seen alive <72 hours before death with no sign of life-threatening disease or symptoms, and when circumstances suggested sudden death such as when the patient was found in bed. Noncardiovascular deaths were defined as all deaths not adjudicated as cardiovascular death. Cardiovascular deaths classified as nonsudden and all noncardiovascular deaths were categorized together as nonsudden deaths.
Statistical Analysis
Baseline characteristics of the age groups were compared with the χ2 test for categorical variables and Kruskal-Wallis test for continuous variables. Outcomes were analyzed with the use of time-to-event methods. All analyses were performed in the intention-to-treat population. The relationship between ICD and survival by age was assessed with linear and spline-based models for effects on the log hazard of death, with separate effects of age estimated in each treatment group. The model with the lowest Akaike information criterion was selected as having the best balance between fit and parsimony.8,9
In addition, a selection impact analysis was performed, describing the expected survival in the full population under different age-based thresholds for ICD treatment assignment.10,11 The selection impact estimate is nonparametric because each time point represents a weighed combination of Kaplan-Meier estimates from the relevant treatment groups. Thus, the overall survival for the population, including both the patients who received an ICD and those who did not, is estimated. For example, the estimated effect of assigning patients ≤50 years of age to ICD is the weighted average of the Kaplan-Meier estimates for survival in the ICD arm for patients ≤50 years of age and in the control arm for patients >50 years of age, with the average weighed by the proportions of patients in the corresponding age groups. Ninety-five percent confidence intervals (CIs) were estimated with bootstrapping. Cumulative incidence curves were calculated for all-cause mortality and for cardiovascular death, SCD, and nonsudden death, taking competing risks into account. Formal assessment of proportional hazard did not find significant nonproportionality (P=0.23). Differences in the distribution of mode of death between age groups were assessed with frequency tables and the χ2 test. Incidences rates were estimated by Poisson regression and are expressed as events per 100 patient-years. In a multivariable Cox regression model, we tested the interaction between age and treatment strategy, controlling for known risk factors. Two-sided values of P<0.05 were considered statistically significant. All analyses were performed with SAS software version 9.4 (SAS Institute) and R software version 3.3.1 (R Project for Statistical Computing).
Results
Baseline characteristics for the age tertiles are presented in the Table. Median age of the study population was 63 years (range, 21–84 years; Figure 1). The oldest age group had a significantly higher prevalence of comorbidities, a longer duration of heart failure, and an adverse biomarker profile (NT-proBNP and lower renal function [estimated glomerular filtration rate]), and slightly fewer received target doses of guideline therapy. The median follow-up time for the entire population was 67.6 months, with no difference between groups. Baseline characteristics for patients according to age tertiles and randomization for those ≤68 and >68 years and ≤70 and >70 years of age are presented in Tables I through III in the online-only Data Supplement.
| Age Group 1, <59 y (n=348) | Age Group 2, 59–<68 y (n=375) | Age Group 3, ≥68 y (n=393) | P Value | |
|---|---|---|---|---|
| Median age (IQR), y | 53 (47–56) | 63 (61–65) | 73 (70–76) | … |
| Randomized to ICD, n (%) | 167 (48) | 173 (46) | 216 (55) | 0.04 |
| Men, n (%) | 260 (75) | 273 (73) | 276 (70) | 0.39 |
| Median blood pressure (IQR), mm Hg | ||||
| Systolic | 120 (109–136) | 123 (110–137) | 126 (113–140) | 0.02 |
| Diastolic | 74 (68–83) | 74 (65–81) | 73 (65–80) | 0.02 |
| Median BMI (IQR), kg/m2 | 27 (24–31) | 27 (24–30) | 26 (24–29) | 0.004 |
| Median NT-proBNP (IQR), pg/mL | 817 (446–1692) | 1245 (658–2307) | 1466 (724–2682) | <0.0001 |
| Median QRS complex duration (IQR), ms | 132 (102–162) | 145 (112–166) | 150 (120–166) | <0.0001 |
| Median LVEF (IQR), % | 24 (19–30) | 25 (20–30) | 25 (20–30) | 0.03 |
| Median eGFR (IQR), mL·min−1·1.73 m−2 | 87 (71–101) | 73 (59–90) | 63 (50–78) | <0.0001 |
| NYHA class, n (%) | <0.0003 | |||
| II | 216 (62) | 201 (54) | 180 (46) | |
| III | 130 (37) | 170 (45) | 205 (52) | |
| IV | 2 (1) | 4 (1) | 8 (2) | |
| Median duration of heart failure (IQR), mo | 12 (7–40) | 18 (8–72) | 25 (11–75) | <0.0001 |
| Coexisting conditions, n (%) | ||||
| Hypertension | 74 (21) | 127 (34) | 147 (37) | <0.0001 |
| Permanent atrial fibrillation | 45 (13) | 86 (23) | 117 (30) | <0.0001 |
| Diabetes mellitus | 54 (16) | 83 (22) | 76 (19) | 0.08 |
| Cause of heart failure, n (%) | 0.004 | |||
| Idiopathic | 274 (79) | 286 (76) | 289 (74) | |
| Valvular | 12 (3) | 10 (3) | 19 (5) | |
| Hypertension | 19 (5) | 48 (13) | 50 (13) | |
| Other | 43 (12) | 31 (8) | 35 (9) | |
| Medication, n (%) | ||||
| β-Blocker | 324 (93) | 345 (92) | 357 (91) | 0.53 |
| ACE inhibitor or ARB | 343 (99) | 361 (96) | 373 (95) | 0.03 |
| MRA | 228 (66) | 217 (58) | 201 (51) | 0.0004 |
| Amiodarone | 15 (4) | 27 (7) | 24 (6) | 0.25 |
| CRT, n (%) | 181 (52) | 210 (56) | 254 (65) | 0.002 |
| Preexisting pacemaker or CRT-pacemaker, n (%) | 20 (6) | 30 (8) | 52 (13) | 0.001 |
Figure 1. Age distribution for the study population from the DANISH trial (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter-Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality). White, gray, and black bars illustrate the age tertiles.
Figure 2 shows the relation between age and risk of all-cause mortality comparing ICD treatment and control. Increasing the model complexity beyond a linear relationship with age did not sufficiently improve model fit to justify the additional model complexity. Each year of younger age was associated with a 3.0% (95% CI, 0.03–6.0; P=0.03) further reduction in the hazard ratio (HR) for the benefit of an ICD, and the point estimate crossed 1.0 at just after 70 years of age.
Figure 2. Relation between age and risk of all-cause mortality for implantable cardioverter-defibrillator (ICD) treatment or control. Shown is the linear relationship between age and survival of patients by ICD implantation. The x axis shows age in years; the y axis, hazard ratios (HRs). Dashed gray horizontal line indicates HR=1, which corresponds to an equal mortality in patients treated with an ICD and control. The full black line illustrates risk for all-cause mortality according to age, and dashed gray lines show the 95% confidence interval.
The selection impact curve is presented in Figure 3. Each point on the curve shows the estimated total 7-year survival for the population in case this specific age was chosen as the cutoff for ICD treatment. The 7-year survival rate in the overall population is estimated at 70% if no one received an ICD and at 72% if everyone received an ICD. The maximum survival rate of the entire population was estimated with a cutoff of ≤70 years for ICD implantation, with 75% surviving. A cutoff at ≤70 years was therefore used for further analysis of modes of death. A selection impact analysis with 1-year age intervals, depicting age ≤70 years as the highest age cutoff with significant survival benefit for the entire population, is shown in Figure I in the online-only Data Supplement.
Figure 3. Selection impact curve to describe the expected survival in the full population under different age-based thresholds for implantable cardioverter-defibrillator (ICD) treatment assignment. Each point (black circle) shows the total 7-year survival in the population if this age is chosen as cutoff for ICD treatment. Gray vertical lines show the 95% confidence interval. The estimate is nonparametric because each point on the curve is a weighted combination of Kaplan-Meier estimates from the relevant treatment groups. The survival in the entire population is 75% when ICD implementation is restricted to patients ≤70 years of age. The graph does not show survival rates for patients with the specified ages along the horizontal axis but rather the survival rate in the entire population when ICD use is assigned on the basis of the different age thresholds.
In Figure 4, the time-to-event curves for all-cause mortality are stratified by the cutoff of ≤70 years. Patients ≤70 years of age had significantly better survival when treated with an ICD (HR, 0.70; 95% CI, 0.51–0.96; P=0.03). After 7 years of follow-up, patients with an ICD had 8% lower absolute mortality (1.1%/y). For patients >70 years old, ICD implantation was not associated with improved all-cause mortality (HR, 1.05; 95% CI, 0.68–1.62; P=0.84). In a multivariable model adjusted for sex, CRT, body mass index, NT-proBNP, estimated glomerular filtration rate, New York Heart Association class, duration of heart failure, hypertension, diabetes mellitus, atrial fibrillation, and use of β-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and mineralocorticoid-receptor antagonist, ICD was significantly associated with improved survival (P=0.02) for patients <70 years of age.
Figure 4. All-cause mortality for the entire population in (A) patients ≤70 years old and (B) patients >70 years old. Black lines represent patients in the control group; gray lines, patients randomized to implantable cardioverter-defibrillator (ICD) treatment.
Figure 5 shows the cumulative rates of SCD and nonsudden death in the control group only. Among patients ≤70 years of age randomized to the control group, the incidence rate of SCD was 1.8 (95% CI, 1.3–2.5) and for nonsudden death was 2.7 (95% CI, 2.1–3.5) events per 100 patient-years. In contrast, for patients >70 years of age, the incidence rate for SCD was 1.6 (95% CI, 0.8–3.2) and for nonsudden death was 5.4 (95% CI, 3.7–7.8) events per 100 patient years. This difference in distribution of mode of death was statistically significant (P=0.01). The corresponding cumulative rates of SCD and nonsudden death for patients randomized to ICD treatment are presented in Figure 6. Figures II and III in the online-only Data Supplement show the risk of SCD and nonsudden death, respectively, according treatment with ICD or control for patients ≤70 and >70 years of age.
Figure 5. Cumulated event rates of causes of death in the control group for (A) patients ≤70 years old and (B) patients >70 years old. For both graphs, gray lines indicate nonsudden death, and black lines indicate sudden cardiac death (SCD). Among patients <70 years old, 96 patients died: 38 SCDs and 58 nonsudden deaths. Among patients >70 years old, 35 patients died: 8 SCDs and 27 nonsudden deaths.
Figure 6. Cumulated event rates of causes of death in the implantable cardioverter-defibrillator (ICD)–treated group for (A) patients ≤70 years and (B) patients >70 years old. In both graphs, gray lines indicate nonsudden deaths and black lines indicate sudden cardiac deaths (SCDs). Among patients <70 years old, 65 patients died: 13 SCDs and 52 nonsudden deaths. Among patients >70 years old, 55 patients died: 11 SCDs and 44 of nonsudden deaths.
A successful ICD shock was experienced by 46 patients <70 years of age and 10 patients >70 years of age. The cumulative incidence of first successful ICD shock after 7 years of follow-up was 0.72% (95% CI, 0.66–0.78) for patients <70 years of age compared with 0.48% (95% CI, 0.39–0.61) for patients >70 years of age.
All results reported with age ≤70 years as the cutoff were similar if age ≤68 years was used instead with no changes in statistical significance.
Discussion
In this study in patients with nonischemic systolic heart failure, the association between the ICD and all-cause mortality decreased with advancing age in a linear relation, and no association between the ICD and survival was observed in older patients. Modes of death vary with age, and although sudden death rates were roughly similar between younger and older patients, the rate of nonsudden death was twice as high in the older population.
Limited data exist on the relation between the ICD and all-cause mortality by age. A previous meta-analysis found a survival benefit of ICD implantation for all patients, but with benefit decreasing with increasing age.12 In the current international guidelines, implantation of an ICD is recommended for patients with systolic heart failure regardless of pathogenesis and age.13,14 Meta-analyses of all trials of patients with nonischemic systolic heart failure, including the results of the DANISH study, found a significant reduction in all-cause mortality for the entire population.15,16 However, the result from our study suggests that ICD implantation in patients with nonischemic systolic heart failure significantly decreases all-cause mortality only in the younger patients. This is in accordance with a meta-analysis of the MADIT II trial (Multicenter Automatic Defibrillator Implantation II), SCD-HeFT trial (Sudden Cardiac Death in Heart Failure), and DEFINITE trial (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation), which showed that age may be associated with the benefit of an ICD with a smaller reduction in all-cause mortality in older compared with younger patients.17
For an ICD to prevent death, the underlying cause must be arrhythmic. Therefore, the potential benefit of ICD implantation depends on a patient’s risk of SCD relative to the risk of nonsudden death. Correspondingly, we found no association between ICD and nonsudden death regardless of age. The potential benefit of ICD implantation therefore depends on a patient’s risk of SCD relative to the risk of nonsudden death. In the present study, we investigated the modes of death in patients not treated with an ICD. Older patients were twice as likely as younger patients to die of causes other than SCD, and consequently, SCD accounted for a higher proportion of deaths among the younger patients than the older patients. This pattern was also seen in an analysis of >6000 patients with structural heart disease, primarily heart failure caused by coronary artery disease, in which death resulting from any cause increased with age whereas the incidence of SCD decreased.6 All this may explain why ICD implantation has less impact in older patients. A dichotomous age cutoff for effect of an ICD will be arbitrary, but our analyses suggest an optimal cutoff of ≤70 years of age in the population randomized in the DANISH study. However, because other factors may also be of importance when ICD implantation is considered, a rigid age cutoff should not be stated. Overall, the mortality rates in DANISH were lower than in previous studies addressing ICD implantation.18,19
Many factors are important in the consideration of ICD implantation. First, patients’ preferences should be taken into account. Studies have shown that patients with heart failure express different preferences concerning treatment strategy according to age. Younger patients often emphasize longer life expectancy and prefer increased survival time, whereas older patients consider quality of life of greater importance.20 Second, balance between the potential benefits and risks of ICD implantation is important. ICD implantation is an invasive procedure with risk of perioperative complications such as pneumothorax, bleeding, and cardiac perforation, and late complications associated with ICD treatment such as inappropriate shocks, device-related infection, the fear of appropriate shocks, and quality of life are to be considered.21 Consequently, risk stratification techniques are needed to adequately optimize the risk/benefit balance of ICD implantation in individual patients.22 In this study, the patients in the oldest age group presented worse on almost all clinical parameters. A worse risk factor profile might be associated with modes of death and outcomes of an ICD and should be taken into account before ICD implantation.
Limitations
In the present analysis, the bulk of patients were between 40 and 80 years old, with very few patients outside this range. Consequently, conclusions outside this age span are based on extrapolations. We found the highest survival for the entire population with ICD implantation in patients ≤70 years of age, but confidence limits of the estimate were wide, and we cannot conclude that age ≤70 years is significantly superior to any other age cutoff. As in any clinical trial, patient selection may be an issue, and selection bias might be more pronounced with age. Consequently, 68% of patients >70 years of age who were included in DANISH were scheduled for CRT, and this might have affected our results. In addition, this is a subgroup analysis, and randomization to ICD or control was not stratified by age. Randomization was not blinded because of the surgical procedure, and this may have influenced the clinical treatment strategy afterward. CRT was implanted in 58% of the patients (and in 68% of patients >70 years of age), which may have influenced our findings. The inclusion criteria of NT-proBNP did not change according to age, which might have influenced the risk and severity of heart disease in the older population and thereby also modes of death.
All this must be borne in mind in the interpretation of our results and before they are applied in clinical practice.
Conclusions
In this post hoc analysis of the DANISH study, ICD implantation was associated with reduced all-cause mortality in patients ≤70 years of age. The benefit of ICD implantation decreased with older age and was not apparent in patients >70 years of age. Older patients were more likely to die of causes other than SCD compared with younger patients, which might be a reason for the diminishing association between ICD implantation and all-cause mortality with advancing age.
Sources of Funding
The DANISH trial was supported by unrestricted grants from Medtronic, St Jude Medical, Tryg Fonden, and the Danish Heart Foundation.
Disclosures
Dr Nielsen is supported by the Novo Nordisk Foundation (NNF16OC0018658). Dr Svendsen reports grants, personal fees, and other from Medtronic and Biotronic; personal fees from AstraZeneca, Boehringer Ingelheim, and Bayer; and grants from Gilead and St Jude Medical. The other authors report no conflicts.
Footnotes
References
- 1.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després J-P, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB , American Heart Association Statistics Committee, Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association.Circulation. 2016; 133:e38–e360.LinkGoogle Scholar - 2.
Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML ; Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.N Engl J Med. 2002; 346:877–883. doi: 10.1056/NEJMoa013474.CrossrefMedlineGoogle Scholar - 3.
Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Gustafsson F, Egstrup K, Videbæk R, Hassager C, Svendsen JH, Høfsten DE, Torp-Pedersen C, Pehrson S ; DANISH Investigators. Defibrillator implantation in patients with nonischemic systolic heart failure.N Engl J Med. 2016; 375:1221–1230. doi: 10.1056/NEJMoa1608029.CrossrefMedlineGoogle Scholar - 4.
Rickenbacher P, Pfisterer M, Burkard T, Kiowski W, Follath F, Burckhardt D, Schindler R, Brunner-La Rocca HP ; TIME-CHF Investigators. Why and how do elderly patients with heart failure die? Insights from the TIME-CHF study.Eur J Heart Fail. 2012; 14:1218–1229. doi: 10.1093/eurjhf/hfs113.CrossrefMedlineGoogle Scholar - 5.
Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, Greene HL, Boczor S, Domanski M, Follmann D, Gent M, Roberts RS . Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials: AVID, CASH and CIDS studies: Antiarrhythmics vs Implantable Defibrillator Study, Cardiac Arrest Study Hamburg, Canadian Implantable Defibrillator Study.Eur Heart J. 2000; 21:2071–2078. doi: 10.1053/euhj.2000.2476.CrossrefMedlineGoogle Scholar - 6.
Krahn AD, Connolly SJ, Roberts RS, Gent M ; ATMA Investigators. Diminishing proportional risk of sudden death with advancing age: implications for prevention of sudden death.Am Heart J. 2004; 147:837–840. doi: 10.1016/j.ahj.2003.12.017.CrossrefMedlineGoogle Scholar - 7.
Thune JJ, Pehrson S, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Egstrup K, Hastrup-Svendsen J, Høfsten DE, Torp-Pedersen C, Køber L . Rationale, design, and baseline characteristics of the DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillators in patients with non-ischemic Systolic Heart failure on mortality (DANISH).Am Heart J. 2016; 179:136–141. doi: 10.1016/j.ahj.2016.06.016.CrossrefMedlineGoogle Scholar - 8.
Sakamoto Y . Akaike Information Criterion Statistics. D Reidel Publishing Company: James T. Austin 903; 1988.Google Scholar - 9.
Akaike H . A new look at the statistical model identification.IEEE Trans Autom Control. 1974; 19:716–723.CrossrefGoogle Scholar - 10.
Song X, Pepe MS . Evaluating markers for selecting a patient’s treatment.Biometrics. 2004; 60:874–883. doi: 10.1111/j.0006-341X.2004.00242.x.CrossrefMedlineGoogle Scholar - 11.
Song X, Zhou XH . Evaluating markers for treatment selection based on survival time.Stat Med. 2011; 30:2251–2264. doi: 10.1002/sim.4258.CrossrefMedlineGoogle Scholar - 12.
Hess PL, Al-Khatib SM, Han JY, Edwards R, Bardy GH, Bigger JT, Buxton A, Cappato R, Dorian P, Hallstrom A, Kadish AH, Kudenchuk PJ, Lee KL, Mark DB, Moss AJ, Steinman R, Inoue LY, Sanders G . Survival benefit of the primary prevention implantable cardioverter-defibrillator among older patients: does age matter? An analysis of pooled data from 5 clinical trials.Circ Cardiovasc Qual Outcomes. 2015; 8:179–186. doi: 10.1161/CIRCOUTCOMES.114.001306.LinkGoogle Scholar - 13.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P . 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC): developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur J Heart Fail. 2016; 18:891–975. doi: 10.1002/ejhf.592.CrossrefMedlineGoogle Scholar - 14.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL . 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2013; 128:1810–1852. doi: 10.1161/CIR.0b013e31829e8807.LinkGoogle Scholar - 15.
Golwala H, Bajaj NS, Arora G, Arora P . Implantable cardioverter-defibrillator for nonischemic cardiomyopathy: an updated meta-analysis.Circulation. 2017; 135:201–203. doi: 10.1161./CIRCULATIONAHA.116.026056.LinkGoogle Scholar - 16.
Al-Khatib SM, Fonarow GC, Joglar JA, Inoue LYT, Mark DB, Lee KL, Kadish A, Bardy G, Sanders GD . Primary prevention implantable cardioverter defibrillators in patients with nonischemic cardiomyopathy: a meta-analysis.JAMA Cardiol. 2017; 2:685–688. doi: 10.1001/jamacardio.2017.0630.CrossrefMedlineGoogle Scholar - 17.
Santangeli P, Di Biase L, Dello Russo A, Casella M, Bartoletti S, Santarelli P, Pelargonio G, Natale A . Meta-analysis: age and effectiveness of prophylactic implantable cardioverter-defibrillators.Ann Intern Med. 2010; 153:592–599. doi: 10.7326/0003-4819-153-9-201011020-00009.CrossrefMedlineGoogle Scholar - 18.
Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH ; Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.N Engl J Med. 2005; 352:225–237. doi: 10.1056/NEJMoa043399.CrossrefMedlineGoogle Scholar - 19.
Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH ; Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.N Engl J Med. 2004; 350:2151–2158. doi: 10.1056/NEJMoa033088.CrossrefMedlineGoogle Scholar - 20.
Lewis EF, Johnson PA, Johnson W, Collins C, Griffin L, Stevenson LW . Preferences for quality of life or survival expressed by patients with heart failure.J Heart Lung Transplant. 2001; 20:1016–1024.CrossrefMedlineGoogle Scholar - 21.
Ezzat VA, Lee V, Ahsan S, Chow AW, Segal O, Rowland E, Lowe MD, Lambiase PD . A systematic review of ICD complications in randomised controlled trials versus registries: is our ‘real-world’ data an underestimation?Open Heart. 2015; 2:e000198. doi: 10.1136/openhrt-2014-000198.CrossrefMedlineGoogle Scholar - 22.
Barra S, Providência R, Paiva L, Heck P, Agarwal S . Implantable cardioverter-defibrillators in the elderly: rationale and specific age-related considerations.Europace. 2015; 17:174–186. doi: 10.1093/europace/euu296.CrossrefMedlineGoogle Scholar
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