Implantable Cardioverter-defibrillator Implantation For Primary Prevention Research Articles

Cardiac sympathetic innervation assessed with 123I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator

BackgroundScintigraphy with iodine-123-metaiodobenzylguanidine (123I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if 123I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with 123I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Material and methodsSeventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent 123I-MIBG to assess CSI (heart-to-mediastinum ratio – HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of 123I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. ResultsDuring a mean follow-up of 19.5 [9.3–29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). ConclusionsDiabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless 123I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients.

Impact of early complications on outcomes in patients with implantable cardioverter-defibrillator for primary prevention

The lifesaving benefit of implantable cardioverter-defibrillators (ICDs) has been demonstrated. Their use has increased considerably in the past decade, but related complications have become a major concern. The purpose of this study was to assess the incidence and effect on outcomes of early (≤30 days) complications after ICD implantation for primary prevention in a large French population. We analyzed data from 5539 patients from the multicenter French DAI-PP (Défibrillateur Automatique Implantable-Prévention Primaire) registry (2002-2012) who had coronary artery disease or dilated cardiomyopathy and were implanted with an ICD for primary prevention. Overall, early complications occurred in 707 patients (13.5%), mainly related to lead dislodgment or hematoma (57%). Independent factors associated with occurrence of early complications were severe renal impairment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.17-2.37, P = .02), age ≥75 years (OR 1.01, 95% CI 1.00-1.02, P = .03), cardiac resynchronization therapy (OR 1.58, 95% CI 1.16-2.17, P = .01), and anticoagulant therapy (OR 1.28, 95% CI 1.02-1.61, P = .03). During a mean ± SD follow-up of 3.1 ± 2.3 years, 824 (15.8%) patients experienced ≥1 late complication (>30 days), and 782 (14.9%) patients died. After adjustment, early complications remained associated with occurrence of late complications (OR 2.15, 95% CI 1.73-2.66, P < .0001) and mortality (OR 1.70, 95% CI 1.34-2.17, P = .003). Early complications are common after ICD implantation for primary prevention, occurring in 1 in 7 patients, and are associated with an increased risk of late complications and overall mortality. Further studies are needed to investigate the underlying mechanisms of such associations.

Geriatric Conditions in Patients Undergoing Defibrillator Implantation for Prevention of Sudden Cardiac Death

Geriatric conditions may influence outcomes among patients receiving implantable cardioverter-defibrillators (ICDs). We sought to determine the prevalence of frailty and dementia among older adults receiving primary prevention ICDs and to determine the impact of multimorbidity on mortality within 1 year of ICD implantation. The cohort included 83 792 Medicare patients from the National Cardiovascular Data Registry ICD Registry who underwent first primary prevention ICD implantation between 2006 and 2009. These data were merged with Medicare analytic files to determine the prevalence of frailty, dementia, and other conditions before ICD implantation, as well as 1-year mortality. A validated claim-based algorithm was used to identify frail patients. Mutually exclusive patterns of chronic conditions were examined. The association of each pattern with 1-year mortality was assessed using logistic regression models adjusted for selected patient characteristics. Approximately 1 in 10 Medicare patients with heart failure receiving a primary prevention ICD had frailty (10%) or dementia (1%). One-year mortality was 22% for patients with frailty, 27% for patients with dementia, and 12% in the overall cohort. Several multimorbidity patterns were associated with high 1-year mortality rates: dementia with frailty (29%), frailty with chronic obstructive pulmonary disease (25%), and frailty with diabetes mellitus (23%). These patterns were present in 8% of the cohort. More than 10% of Medicare beneficiaries with heart failure receiving primary prevention ICDs have frailty or dementia. These patients had significantly higher 1-year mortality than those with other common chronic conditions. Frailty and dementia should be considered in clinical decision-making and guideline development.

Outcomes following the implantation of cardioverter-defibrillator for primary prevention in transposition of the great arteries after intra-atrial baffle repair: a single-centre experience.

Patients with D-loop transposition of the great arteries (D-TGA) status post intra-atrial baffling are at an increased risk for sudden cardiac arrest. The benefit of primary implantable cardioverter-defibrillator (ICD) implantation in these patients is questionable due to high burden of adverse events. We aimed to evaluate the incidence and causes of all types of device shocks, as well as of device-related complications among patients with D-TGA implanted with ICDs for primary prevention. Retrospective analysis of all patients with D-TGA who underwent atrial switch procedure and ICD implantation for primary prevention. Eighteen patients (83% males) were identified. Average age at atrial switch was 2.5 years (range 0.1-17) and at ICD implantation 26 years (15-41). During a median follow-up of 4 years, 10 patients (55%) received shocks for non-ventricular arrhythmic events, whereas 1 patient was shocked for ventricular tachycardia, for an annual rate of shock delivery of 7.1%. The most common cause for shock delivery was the occurrence of atrial arrhythmias, mostly in the form of atrial flutter. Elevated systemic ventricular end-diastolic pressures were found to be associated with an increased risk for inappropriate shocks. Five patients (28%) required lead extraction and three required generator change due to device recalls during follow-up. Atrial arrhythmias were the most common cause for ICD shocks in a primary prevention population, while ventricular tachycardia was infrequent. The association between elevated end-diastolic pressures and the occurrence of arrhythmias demonstrates the close mechano-electrical relationship in D-TGA and may be an important predictor of arrhythmic events.

Association of Implantable Cardioverter Defibrillator Therapy with All-Cause Mortality-A Systematic Review and Meta-Analysis.

Implantable cardioverter defibrillators (ICDs) have become the standard approach for prevention of sudden cardiac death. Whether ICD therapy is an independent predictor of all-cause mortality is controversial. We made the systematic review and meta-analysis to estimate the impact of ICD therapy on mortality. We searched the PubMed and Embase databases for studies evaluating the effect of ICD shocks or antitachycardia pacing (ATP) on mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random effects models. Thirteen cohort studies were identified. Mean ejection fraction of the population was 23-35%; 68.0% had ischemic etiology, and 74.5% received a primary prevention ICD implantation. Appropriate shocks were an independent predictor of increased mortality compared with no-shock or no-therapy patients (HR 2.07, 2.76, respectively). In contrast, inconsistent results were obtained during inappropriate-shock analyses: when compared with no-shock patients, inappropriate shocks were associated with an increased risk of death (HR 1.54, 95% CI: 1.25-1.89, P < 0.0001); however, when compared to no-therapy patients, there was no relationship between inappropriate shocks and mortality (HR 1.20, 95% CI: 0.90-1.61, P = 0.22). Subgroup analysis in heart failure patients also did not find any difference in mortality between inappropriate-shock and no-therapy patients. No increased risk of mortality was found in the patients who experienced appropriate or inappropriate ATP only. Appropriate shocks were associated with an increased mortality in ICD patients. However, whether inappropriate shocks worsened the clinical outcome was controversial, and larger prospective trials are needed to clarify the issue.

Abstract 17128: Primary Prevention With Implantable Cardioverter Defibrillator in High-risk Long-QT Syndrome Patients

Background: Implantable cardioverter defibrillator (ICD) is currently indicated for the treatment of long QT syndrome (LQTS) patients who survived aborted cardiac arrest. However, data regarding the role of ICD in primary prevention in patients with LQTS is scarce. Methods: The study population comprised 212 LQTS patients (65% genotype positive) from the Rochester LQTS Registry who had ICD implantation for primary prevention. Cox regression model was used to identify clinical variables that were associated with appropriate shock and inappropriate shock. The efficacy of β-blockers was determined using a time-dependent analysis. Results: During a median follow up time of 9.2±4.9 years the cumulative event rates of appropriate shocks and inappropriate shocks were 23% and 34% respectively. In the entire cohort appropriate shock was associated with QTc ≥ 550 msec (HR=3.94; CI 2.08-7.46; p&lt;0.001) and prior syncope on β-blockers (HR=1.92;(CI 1.01-3.65, p=0.047), β-blockers trended to be protective (HR=0.52; CI 0.26-1.07; p=0.075). Importantly, prior syncope was only important if it happened while on β-blockers. Inappropriate shock was significantly associated with age below 15 at implantation (HR=1.94; CI 1.11-3.38; p=0.019). In patients with positive genotype, appropriate shock was associated with QTc ≥ 550 msec (HR=5.37; CI 2.38-12.10; p&lt;0.001), implantation age ≤ 15 years (HR=2.77; CI 1.08-7.11; p=0.034), LQT2 vs. LQT1 (HR=2.47; CI 0.93-6.52; p=0.069), and multiple mutations vs. LQT1 (HR=2.87; CI 0.88-9.42; p=0.081); β-blockers were significantly protective (HR=0.23, CI 0.09-0.59, p=0.002). Conclusions: Among LQTS patients in whom ICD is implanted for primary prevention, QTc duration and history of syncope while on β-blockers therapy are associated increased risk for appropriate shock. β-blocker treatment remains important in this high-risk group. Those with an ICD implanted before age 15 were at a higher risk of receiving an inappropriate shock.

Abstract 12621: Gender Differences Among Implantable Cardioverter Defibrillators Recipients in the Setting of Primary Prevention

Background: Data regarding sex specificities in the use, benefits and complications of implantable cardioverter-defibrillators (ICDs) in primary prevention in the real-world European setting are sparse. Methods: Using a large multicentric cohort of consecutive patients referred for ICD implantation for primary prevention (2002-2012), in the setting of coronary artery disease or dilated cardiomyopathy, we examined potential sex differences in subjects’ characteristics and outcomes. Results: Of 5,539 patients, only 837 (15.1%) were women and 53.8% received cardiac resynchronization therapy (CRT-D). Compared to men, women presented a significantly higher proportion of dilated cardiomyopathy (60.2% vs. 36.2%, P120ms: 74.6% vs. 68.5%, P=0.003), higher New York Heart Association functional class (2.5±0.7 vs. 2.4±0.7, P=0.003) and lower prevalence of atrial fibrillation (18.7% vs. 24.9%, P&lt;0.001). During a 16,786 patient-years follow-up, overall, fewer appropriate therapies were observed in women (HR = 0.59, CI95% 0.45-0.76; P&lt;0.001). By contrast, no sex-specific interaction was observed for inappropriate shocks (OR for women = 1.00, 95%CI 0.74-1.35, P=0.997) and mortality (HR = 0.87; 95%CI 0.66-1.15, P=0.324), with similar patterns of cause of deaths. Conclusion: In our real life registry, women account for the minority of ICD recipients. While female ICD recipients present with features of more severe heart failure in the setting of primary prevention of sudden cardiac death, we observed they have a 40% lower incidence of appropriate therapies.

Remarks on polyparametric assessment of sudden death risk for primary prevention ICD implantation in patients with left ventricular dysfunction of ischemic and non ischemic etiology. Italian Association of Hospital Cardiologists (ANMCO) Experts Position Paper

It is generally recognized that current guidelines, based on ejection fraction criteria, do not allow appropriate selection of patients for implantable cardioverter-defibrillator (ICD) therapy in the primary prevention of sudden death, thus hindering the optimal use of ICD in patients with left ventricular dysfunction of ischemic and nonischemic etiology. Ejection fraction alone has limitations in both sensitivity and specificity. Assessment of the risk for sudden death using a combination of multiple tests (ejection fraction associated with one or more different arrhythmic risk markers) could partially compensate for these limitations. In this position paper, the potential usefulness of a polyparametric assessment using some of the most investigated risk markers of sudden death is discussed, including late gadolinium enhancement cardiac magnetic resonance, programmed ventricular stimulation, T-wave alternans, autonomic tone, biomarkers, and genetic testing.

Cardiac sympathetic innervation assessed with (123)I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator.

Scintigraphy with iodine-123-metaiodobenzylguanidine ((123)I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if (123)I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with (123)I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Seventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent (123)I-MIBG to assess CSI (heart-to-mediastinum ratio - HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of (123)I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. During a mean follow-up of 19.5 [9.3-29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). Diabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless (123)I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients.

Serum amine-based metabolites and their association with outcomes in primary prevention implantable cardioverter-defibrillator patients.

Heart failure patients are at increased risk of ventricular arrhythmias and all-cause mortality. However, existing clinical and serum markers only modestly predict these adverse events. We sought to use metabolic profiling to identify novel biomarkers in two independent prospective cohorts of patients with implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death (SCD). Baseline serum was quantitatively profiled for 42 known biologically relevant amine-based metabolites among 402 patients from the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) Study (derivation group) and 240 patients from the Genetic Risk Assessment of Defibrillator Events (GRADE) Study (validation group) for ventricular arrhythmia-induced ICD shocks and all-cause mortality. Three amines, N-methyl-l-histidine, symmetric dimethylarginine (SDMA), and l-kynurenine, were derived and validated to be associated with all-cause mortality. The hazard ratios of mortality in PROSE-ICD and GRADE were 1.48 (95% confidence interval 1.14-1.92) and 1.67 (1.22-2.27) for N-methyl-l-histidine, 1.49 (1.17-1.91) and 1.77 (1.27-2.45) for SDMA, 1.31 (1.06-1.63) and 1.73 (1.32-2.27) for l-kynurenine, respectively. l-Histidine, SDMA, and l-kynurenine were associated with ventricular arrhythmia-induced ICD shocks in PROSE-ICD, but they did not reach statistical significance in the GRADE cohort. Utilizing metabolic profiling in two independent prospective cohorts of patients undergoing ICD implantation for primary prevention of SCD, we identified several novel amine markers that were associated with appropriate shock and mortality. These findings shed insight into the potential biologic pathways leading to adverse events in ICD patients. Further studies are needed to confirm the prognostic value of these findings.

Distribution of Ventricular Fibrosis Associated With Life-Threatening Ventricular Tachyarrhythmias in Patients With Nonischemic Dilated Cardiomyopathy.

Current guidelines recommend the implantation of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) in a subgroup of patients with nonischemic cardiomyopathy (NICM) who have a left ventricular ejection fraction (LVEF) ≤ 30-35%, and are NYHA functional class II or III. However, the majority of patients with an ICD implantation for primary prevention did not receive appropriate ICD therapy. The purpose of this study was to evaluate the association between myocardial fibrosis detected by cardiovascular magnetic resonance (CMR) imaging and life-threatening ventricular arrhythmic events in NICM patients. One hundred and seventy-five NICM patients with an LVEF ≦ 35 % and NYHA functional class II or III, (60 ± 15 years, LVEF 29 ± 5.4%) were studied. Myocardial fibrosis was identified with a late gadolinium enhancement (LGE) on CMR. Clinical events were defined as SCD or life-threatening ventricular arrhythmic events and were followed up for 5.1 ± 3.3 years. The presence of an LGE was detected in 122 patients (70%). No life-threatening ventricular arrhythmia events occurred in patients with the absence of an LGE. A total of 18 ventricular tachycardia and 8 ventricular fibrillation events were found in patients with the presence of an LGE (P < 0.01). Sensitivity, specificity, and positive and negative predictive value of LGE in predicting life-threatening ventricular arrhythmia events were 100%, 34%, and 15% and 100%, respectively. Multivariate analysis showed that the presence of both septal and lateral mid-wall LGE was associated with life-threatening ventricular arrhythmic events (hazard ratio 23.1 CI; 2.88-184.9, P = 0.003). The absence of an LGE predicts a low potential risk of SCD and life-threatening ventricular arrhythmia events in the near future. CMR may be a useful tool for selecting suitable patients for primary ICD implantations in NICM patients.

Changes in Follow-Up Left Ventricular Ejection Fraction Associated With Outcomes in Primary Prevention Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy Device Recipients

BackgroundHeart failure patients with primary prevention implantable cardioverter-defibrillators (ICD) may experience an improvement in left ventricular ejection fraction (LVEF) over time. However, it is unclear how LVEF improvement affects subsequent risk for mortality and sudden cardiac death. ObjectivesThis study sought to assess changes in LVEF after ICD implantation and the implication of these changes on subsequent mortality and ICD shocks. MethodsWe conducted a prospective cohort study of 538 patients with repeated LVEF assessments after ICD implantation for primary prevention of sudden cardiac death. The primary endpoint was appropriate ICD shock defined as a shock for ventricular tachyarrhythmias. The secondary endpoint was all-cause mortality. ResultsOver a mean follow-up of 4.9 years, LVEF decreased in 13.0%, improved in 40.0%, and was unchanged in 47.0% of the patients. In the multivariate Cox models comparing patients with an improved LVEF with those with an unchanged LVEF, the hazard ratios were 0.33 (95% confidence interval: 0.18 to 0.59) for mortality and 0.29 (95% confidence interval: 0.11 to 0.78) for appropriate shock. During follow-up, 25% of patients showed an improvement in LVEF to >35% and their risk of appropriate shock decreased but was not eliminated. ConclusionsAmong primary prevention ICD patients, 40.0% had an improved LVEF during follow-up and 25% had LVEF improved to >35%. Changes in LVEF were inversely associated with all-cause mortality and appropriate shocks for ventricular tachyarrhythmias. In patients whose follow-up LVEF improved to >35%, the risk of an appropriate shock remained but was markedly decreased.

Late arrhythmia in patients with repaired tetralogy of Fallot: who is at risk?

Summary Tetralogy of Fallot (TOF) is the most common cause of cyanotic congenital heart defect. Over the last century, the life expectancy of TOF patients has significantly improved. This, however, has brought new challenges both to patients and their health-care providers, the main of them being late arrhythmia. Ironically, late arrhythmia is predominantly generated due to the fibrotic scars caused by the life-saving surgical repair. Once the first two mainly arrhythmia-free decades after the repair pass, the risk of developing late arrhythmia and, therefore, SCD becomes substantial. Consequently, young adults with repaired Tetralogy of Fallot (rTOF) require careful outpatient monitoring. There have been many attempts to predict the risk of life-threatening arrhythmia in rTOF patients. This has led to the defining of various risk factors, ranging from the widely used QRS prolongation to novel predictors, derived from cardiac magnetic resonance (CMR) based anatomical findings (left ventricular dyssynchrony indexes, right ventricular output tract akinetic length, right ventricular mass-to-volume ratio). The latter predictors have recently established CMR as a tool of high significance in evaluation of rTOF patients. Although the role of Holter monitoring findings in rTOF patient-assessment remains unclear, it may be useful in those who are 25 years and older. Implantable cardioverter–defibrillator (ICD) implantation is the first-line treatment for secondary prevention of sudden cardiac death (SCD). rTOF patients suffer from the highest rate of inappropriate and the lowest rate of appropriate ICD shocks, when compared to other congenital heart diseases. As a consequence, ICD implantation for primary SCD prevention should be carefully weighed. Catheter-based ablation therapy leads to high rate of initial success when abolishing monomorphic ventricular tachycardia and intra-atrial reentrant tachycardia, however recurrence rates remain high.

Quality of Life in Young Adult Patients with a Cardiogenetic Condition Receiving an ICD for Primary Prevention of Sudden Cardiac Death

Prophylactic implantable cardioverter defibrillator (ICD) therapy prevents sudden cardiac death (SCD) among young adults with cardiogenetic conditions, but might reduce quality of life (QoL) due to potential device complications, ongoing medical appointments, and lifestyle restrictions. We investigated QoL in the first year after ICD implantation for the primary prevention of SCD and compared QoL scores with population norms. Consecutive patients with cardiogenetic conditions (aged 18-50 years) referred to the Academic Medical Center in Amsterdam to receive ICD therapy for the primary prevention of SCD between 2007 and 2009 were eligible. Patients completed questions about QoL (Short-Form 36 Health Survey; SF-36), depressive symptoms (Center for Epidemiologic Studies Depression scale; CES-D), anxiety (State-Trait Anxiety Inventory; STAI), and the impact of receiving ICD therapy on lifestyle and work, shortly before ICD implantation and after 2 months, 6 months, and 12 months. Thirty-five of 47 eligible patients participated. QoL was significantly reduced shortly before and 2 months after ICD implantation but improved over time and was comparable with population norms at 6 months and 12 months after ICD implantation. Yet, only about half of the patients believed they had a normal life like everyone else, and 28% had lost or changed their job due to their cardiogenetic condition and ICD therapy. Receiving a diagnosis of a cardiogenetic condition and subsequent ICD implantation was accompanied with a temporarily reduced QoL and a significant negative impact on professional life. Clinicians should inform their patients of the possible QoL consequences when deciding about ICD implantation in primary prevention of SCD in cardiogenetic conditions.

Clinical Impact of Cardiac Magnetic Resonance Imaging Versus Echocardiography-Guided Patient Selection for Primary Prevention Implantable Cardioverter Defibrillator Therapy

The main eligibility criterion for primary prevention implantable cardioverter defibrillator (ICD) therapy, that is, left ventricular ejection fraction (LVEF), is based on large clinical trials using primarily 2-dimensional echocardiography (2DE). Presently, cardiac magnetic resonance imaging (MRI) is considered the gold standard for LVEF assessment. It has been demonstrated that cardiac MRI assessment results in lower LVEFs compared with 2DE. Consequently, cardiac MRI-LVEF assessment may lead to more patients eligible for ICD implantation with potential clinical consequences. The aim of this study was to evaluate the clinical impact of cardiac MRI-LVEF versus 2DE-LVEF assessment for ICD eligibility. A total of 149 patients with cardiac MRI-LVEF ≤35% referred for primary prevention ICD implantation who underwent both 2DE and cardiac MRI-LVEF assessment were retrospectively included. 2DE-LVEF was computed by Simpson's biplane method. Cardiac MRI-LVEF was computed after outlining the endocardial contours in short-axis cine images. Appropriate device therapy (ADT) and all-cause mortality were evaluated during 2.9 ± 1.7years of follow-up. The present study found that cardiac MRI-LVEF was significantly lower compared with 2DE-LVEF (23 ± 8% vs 30 ± 8%, respectively, p <0.001), resulting in 29 (19%) more patients eligible for ICD implantation according to the current guidelines (LVEF ≤35%). Patients with 2DE-LVEF >35% but cardiac MRI-LVEF ≤35% experienced a lower ADT rate compared with patients having 2DE-LVEF ≤35% (2.1% vs 10.4% per year, respectively, p= 0.02). Application of cardiac MRI-LVEF cutoff of 30% resulted in 119 eligible patients experiencing 9.9% per year ADT, comparable with 2DE-LVEF cut-off value of 35%. In conclusion, cardiac MRI-LVEF assessment resulted in more patients eligible for ICD implantation compared with 2DE who showed a relatively low event rate during follow-up. The event rate in patients with cardiac MRI-LVEF ≤30% was comparable with patients having a 2DE-LVEF ≤35%. This study suggests the need for re-evaluation of cardiac MRI-based LVEF cut-off values for ICD eligibility.

The effect of duration of follow-up and presence of competing risk on lifespan-gain from implantable cardioverter defibrillator therapy: who benefits the most?

In at-risk patients with left ventricular dysfunction, implantable cardioverter defibrillators (ICDs) prolong life. Implantable cardioverter defibrillators are increasingly implanted for primary prevention and therefore into lower risk patients. Trial data have demonstrated the benefit of these devices but does not provide an estimate of potential lifespan-gain over longer time periods, e.g. a patient's lifespan. Using data from landmark ICD trials, lifespan-gain was plotted against baseline annual mortality in the individual trials. Lifespan-gain was then extrapolated to a time-horizon of >20 years while adjusting for increasing 'competing' risk from ageing and non-sudden cardiac death (pump failure). At 3 years, directly observed lifespan-gain was strongly dependent on baseline event rate (r = 0.94, P < 0.001). However, projecting beyond the duration of the trial, lifespan-gain increases rapidly and non-linearly with time. At 3 years, it averages 1.7 months, but by 10 years up to 9-fold more. Lifespan-gain over time horizons >20 years were greatest in lower risk patients (∼5 life-years for 5% baseline mortality, ∼2 life-years for 15% baseline mortality). Increased competing risks significantly reduce lifespan-gain from ICD implantation. While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime. Benefit is underestimated when only trial data are assessed as trials can only maintain randomization over limited periods. Lifespan-gain may be further increased through advances in ICD device programming.

Gender and outcomes after primary prevention implantable cardioverter-defibrillator implantation: Findings from the National Cardiovascular Data Registry (NCDR)

Clinical trials have demonstrated the benefit of implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death in selected high-risk individuals. Because of small numbers of women enrolled in these trials, outcomes for women after hospital discharge have not been well described. We compared procedure-related complications and outcomes after hospital discharge between men and women undergoing single- or dual-chamber ICD implantation for primary prevention. In patients 65 years or older with Medicare fee-for-service coverage, we identified 38,912 initial implants (25% women) who received single- or dual-chamber ICDs for primary prevention between January 2006 and December 2009 in the NCDR and evaluated gender differences in outcomes. Women had greater comorbidity and more advanced heart failure (HF) at the time of ICD implantation than did men. Device-related complications, death at 6 months, all-cause readmissions, and HF readmissions at 6 months were significantly more common in women (7.2% vs 4.8%, 6.5% vs 5.6%, 37.2% vs 31.7%, and 14.0% vs 10.0% respectively; P < .001 for all). Women continued to have higher odds of procedural complications (odds ratio [OR] 1.39, 95% CI 1.26-1.53, P < .001), 6-month all-cause readmission (OR 1.22, 95% CI 1.16-1.28, P < .001), and 6-month HF readmission (OR 1.32, 95% CI 1.23-1.42, P < .001), with a trend toward higher 6-month mortality (OR 1.08, 95% CI 0.98-1.20, P = .123), compared with men, after adjusting for differences in baseline characteristics and device type (single vs dual chamber). Among older patients receiving ICDs for primary prevention in clinical practice, women experience worse outcomes than do men. Reasons for gender differences in outcomes are poorly understood and require further investigation.

Prevalence and Outcomes of Patients Receiving Implantable Cardioverter-Defibrillators for Primary Prevention Not Based on Guidelines

Implantable cardioverter-defibrillator (ICD) implantation outside practice guidelines remains contentious, particularly during the mandated waiting periods in patients with recent cardiac events. We assessed the prevalence and outcomes of non-guideline-based (NGB) ICD implantations in a tertiary academic medical center, with a specific focus on adjudication of arrhythmia events. All patients who underwent initial primary prevention ICD implantation at our institution from 2004 to 2012 were categorized as having received guideline-based (GB) or NGB implants and were retrospectively assessed for first episode of appropriate ICD therapy and total mortality. Of 807 patients, 137 (17.0%) received NGB implants. During a median follow-up of 2.9years, patients with NGB implants had similar times to first appropriate ICD therapy (median time to event 1.94 vs 2.17years in patients with GB implants, p= 0.20). After multivariable analysis, patients with NGB implants remained at higher risk for death (hazard ratio 1.54, 95% confidence interval 1.1 to 2.2, p=0.03) but not appropriate ICD therapy (hazard ratio 0.83, 95% confidence interval 0.5 to 1.3, p= 0.51). Furthermore, only 1 of 125 patients who underwent implant within the 40-day waiting period after myocardial infarction or 3-month waiting period after revascularization or cardiomyopathy diagnosis received an appropriate therapy within this period. In conclusion, few patients received NGB ICD implants in our academic medical center. Although these patients have similar long-term risk of receiving appropriate ICD therapy compared with patients with GB implants, this risk is very low during the waiting periods mandated by clinical practice guidelines. These results suggest that there is little need to rush into implanting ICDs during these waiting periods.

Prediction of Nonarrhythmic Mortality in Primary Prevention Implantable Cardioverter-Defibrillator Patients With Ischemic and Nonischemic Cardiomyopathy

ObjectivesThe objective of this study was to investigate the feasibility of identifying heart failure patients who are less likely to benefit from implantable cardioverter-defibrillator (ICD) therapy among those eligible for primary prevention ICDs. BackgroundThe cost-effectiveness of ICDs in primary prevention may be improved dramatically. MethodsUsing a cause-of-death analysis approach, we evaluated the discriminative and predictive values of a risk score with regard to overall mortality and specific causes of death by examining 2,485 patients enrolled in the French Primary Prevention ICD program (2002 to 2012). The risk score included points for New York Heart Association functional class III or greater, age >70 years, QRS duration >120 ms, atrial fibrillation, and glomerular filtration rate <60 ml/min. Sensitivity analyses were performed for ischemic and nonischemic cardiomyopathy, as well as for patients undergoing cardiac resynchronization therapy. ResultsAfter a mean follow-up of 3.0 ± 2.1 years, the overall mortality rate was 5.9 per 100 patient-years (95% confidence interval: 5.4 to 6.5), which increased with the number of risk factors (0 to 5, respectively), as follows: 2.5, 2.9, 4.8, 9.0, 12.3, and 14.8 per 100 patient-years (p < 0.001). The higher mortality rate among patients with the highest scores resulted from an increase in nonarrhythmic mortality (from 2.1 to 14.8 per 100 patient-years, p < 0.001), whereas the occurrence of appropriate ICD therapies did not change significantly across the categories. The C statistic testing of the score was observed to be highly similar for patients with ischemic cardiomyopathy (0.685) and nonischemic cardiomyopathy (0.658) and those receiving cardiac resynchronization therapy (0.678). ConclusionsOur findings suggest the feasibility of and interest in identifying patients eligible for primary prevention ICD implantation who are at significant risk of nonarrhythmic death in the real-world setting.

Effect of Age on Survival and Causes of Death After Primary Prevention Implantable Cardioverter-Defibrillator Implantation

The benefit of implantable cardioverter-defibrillators (ICDs) remains controversial in elderly patients and may be attenuated by a greater risk of nonarrhythmic death. We examined the effect of age on outcomes after prophylactic ICD implantation. All patients with coronary artery disease or dilated cardiomyopathy implanted with an ICD for primary prevention of sudden cardiac death in 12 French medical centers were included in a retrospective observational study. The 5,534 ICD recipients were divided according to age: 18 to 59 years (n = 2,139), 60 to 74 years (n = 2,693), and ≥75 years (n = 702). Greater prevalences of coronary artery disease and atrial fibrillation at the time of implant were observed with increasing age (both p <0.0001). During a mean follow-up of 3.1 ± 2.0 years, the annual mortality rate increased with age: 3.1% per year for age 18 to 59 years, 5.7% per year for age 60 to 74 years, and 7.5% per year for age ≥75 years (p <0.001). Older age was independently associated with a greater risk of death (adjusted odds ratio 1.43, 95% confidence interval 1.14 to 1.80 for age 60 to 74 years; and adjusted odds ratio 1.65, 95% confidence interval 1.22 to 2.22 for age >75 years). Proportions of cardiac deaths (55.2%, 57.6%, and 57.0%, p = 0.84), including ICD-unresponsive sudden death (9.9%, 6.0%, and 10.6%, p = 0.08), and rates of appropriate ICD therapies were similar in the 3 age groups. Older age was independently associated with a higher rate of early complications and a lower rate of inappropriate therapies. In conclusion, older patients exhibited higher global mortality after ICD implantation for primary prevention, whereas rates of sudden deaths and of appropriate device therapies were similar across age groups.