Primary Prevention Implantable Cardioverter-defibrillators Patients Research Articles

Hospital utilisation and the costs associated with complications of ICD implantation in acontemporary primary prevention cohort.

Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. ICD-related complications in anational DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. During amedian follow-up of 28.7months (IQR 25.2-33.7) one or more complications occurred in 13.5% of patients. Acomplication resulted in asurgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7million. Complications following ICD implantation are related to asubstantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.

Health status measured by Kansas City Cardiomyopathy Questionnaire-12 in primary prevention implantable cardioverter defibrillator patients with heart failure

BackgroundSelf-reported health status as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with primary prevention implantable cardioverter defibrillators (ICDs) has mainly been reported from randomized trials. However, these studies are often limited to short follow-up and are subject to selection bias. The aim of this study was to assess KCCQ-12 in patients with primary prevention ICD due to either ischemic or nonischemic heart failure.MethodsThis cross-sectional observational study included all patients in Region Gävleborg, Sweden, who because of primary prevention due to heart failure, had an ICD or underwent device replacement between 2007 and 2017. After validation using medical records patients were sent and returned the KCCQ-12 by regular mail.ResultsA total of 118 questionnaires were analyzed (response rate 71.1%). The mean age was 70.9 ± 9.8 years, and a minority was female (n = 20, 16.9%). The mean overall summary score was 71.5 ± 22.4, there was no significant difference between ischemic and nonischemic heart failure (69.5 ± 23.1 vs. 74.4 ± 21.3; p = 0.195). Atrial fibrillation at baseline was associated with lower score for the domains Symptom frequency (70.2 ± 23.2 vs. 82.2 ± 19.2; p = 0.006) and Social limitation (62.1 ± 26.0 vs. 75.6 ± 26.6; p = 0.006) as well as the overall summary score (63.9 ± 21.3 vs. 74.8 ± 22.2; p = 0.004).ConclusionIn a real-world setting, primary prevention ICD patients with heart failure report an acceptable disease-specific health status at long-term follow-up. Ischemic and nonischemic etiology showed similar health status whereas atrial fibrillation was associated with worse outcome.

Predictors of appropriate shock after generator replacement in patients with an implantable cardioverter defibrillator.

Implantable cardioverter defibrillators (ICDs) are indicated for the primary prevention of sudden cardiac death in patients with reduced left ventricular ejection fraction (LVEF). The ongoing risk/benefit profile of an ICD at generator replacement is unknown. This study aimed to identify predictors of appropriate ICD shocks and therapies after first ICD generator replacement, and its procedure-related complications. We conducted a multicenter, retrospective cohort study including patients with primary prevention ICDs who underwent generator replacement between April 2005 and July 2015 at three Canadian centers. The primary and secondary outcomes were appropriate ICD shock and any appropriate ICD therapy, respectively. Procedure-related complication rates were also reported. Of the 219 patients in the cohort, 61 (28%) experienced an appropriate shock while 40 (18%) experienced appropriate antitachycardia pacing over a median follow up of 2.2 years. Independent predictors of appropriate ICD shocks included: LVEF at time of replacement (adjusted odds ratio [OR] 0.4 per 10% increase in LVEF, P<.001), a history of appropriate ICD shocks prior to replacement (OR 4.9, P<.001), and a history of inappropriate ICD shocks (OR 4.2, 95%, P<.002). Similar predictors were identified for the secondary outcome of any appropriate ICD therapy. Device-related complications were reported in 25 (11%) patients, with 1 (0.5%) resulting in death, 14 (6.3%) requiring site re-operation, and 6 (2.7%) requiring cardiac surgical management. Not all primary prevention ICD patients undergoing generator replacement will require appropriate device therapies afterwards. Generator replacement is associated with several risks that should be weighed against its anticipated benefit. A comprehensive assessment of the risk-benefit profile of patients undergoing generator replacement is warranted.

Impact of COVID-19 Pandemic on Physical Activity in Patients With Implantable Cardioverter-Defibrillators.

The coronavirus disease-2019 (COVID-19) pandemic has been spreading rapidly worldwide since late January 2020. The strict lockdown strategy prompted by the Italian government, to hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreading, has reduced the possibility of performing either outdoor or gym physical activity (PA). This study investigated and quantified the reduction of PA in patients with automatic implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death. Daily PA of 24 patients was estimated by processing recorded data from ICD-embedded accelerometric sensors used by the rate-responsive pacing systems. During the forced 40-d in-home confinement, a mean 25% reduction of PA was observed as compared with the 40-d confinement-free period (1.2 ± 0.3 vs 1.6 ± 0.5 hr/d, respectively, P = .0001). This objective quantification of the impact of the COVID-19 pandemic on PA determined by an ICD device showed an abrupt and statistically significant reduction of PA in primary prevention ICD patients, during the in-home confinement quarantine. To counteract the deleterious effects of physical inactivity during the COVID-19 outbreak, patients should be encouraged to perform indoor exercise-based personalized rehabilitative programs.

Characteristics of ventricular tachyarrhythmias and their susceptibility to antitachycardia pacing termination in patients with ischemic and nonischemic cardiomyopathy: A patient-level meta-analysis of three large clinical trials.

Implantable cardioverter defibrillators (ICDs) reduce all-cause mortality among cardiomyopathy patients. Whether or not antitachycardia pacing (ATP) is equally effective in ischemic (ICM) and nonischemic (NICM) cardiomyopathy patients remains poorly understood. We describe the distribution of monomorphic (MVT) and non-monomorphic (polymorphic ventricular tachycardia/ventricular fibrillation [PVT/VF]) ventricular tachyarrhythmias among ICM and NICM primary prevention patients. This patient-level meta-analysis included primary prevention patients from the Shock-Less (n = 3519), PainFree SST (n = 1917), and PREPARE (n = 690) studies. Distribution of MVT and PVT/VF events were compared with χ2 tests. ATP success was estimated using a generalized estimating equation model to correct for multiple episodes for a patient between cohorts for slow (≥320 ms) and fast (240-310 ms) MVTs. Among 6126 patients, 714 (29% NICM, age 66 ± 13 years, female 18%, EF = 29 ± 12%) had a total of 4444 treated ventricular tachyarrhythmia episodes. The rate of individuals treated for MVT or PVT/VF was comparable between ICM (11.9%) and NICM (11.2%) over 21 ± 10 months. In addition, the distribution of MVT (76% ICM vs. 71% NICM) and PVT/VF (15% ICM vs. 20% NICM) was not significantly different (p = .28). Among MVT episodes, the average tachycardia cycle lengths (332 ± 58 ms ICM vs. 313 ± 40 ms NICM; p = .27) were similar, as was the likelihood of ATP-associated termination (74.6% ICM vs. 76.4% NICM; p = .58). Overall, ATP success was higher for slow (≥320 ms) MVT versus faster (240-310 ms) episodes (84.1% vs. 69%; p < .001). In a large cohort of primary prevention ICD patients, ICM and NICM patients have similar rates and proportions of MVT and PVT/VF episodes. ATP-associated termination of MVT was comparable between the two groups.

P1464A question of gender equality. Sex-related differences in survival after primary prevention implantable cardioverter-defibrillator implantation for dilated cardiomyopathy An analysis from POLKARD

Abstract OnBehalf POLKARD Polish ICD Registry Background The protective effects of implantable cardioverter defibrillators (ICDs) in the primary prevention of sudden cardiac death of patients presenting with left ventricular (LV) systolic dysfunction are unequivocal. Nevertheless, female underrepresentation has been a consistent finding in all randomized controlled primary prevention ICD trials. Surprisingly, there is a vast body of literature on female primary prevention ICD patients exhibit a lower overall mortality. Purpose Therefore, we analyzed data from a large, nationwide POLKARD registry to evaluate the effect of sex on survival after primary prevention cardioverter-defibrillator implantation for dilated cardiomyopathy. Methods All patients enrolled in the Polish ICD Registry from 2008 to 2014 were identified. Patients were included in the study if they were designated as receiving an ICD for primary prevention of SCD after documented non-ischeamic cardiomyopathy. Kaplan-Meier survival analysis was used to assess all-cause mortality. Results Of the 964 ICD recipients, 241 (25%) were women (mean age of 64± 0,45 years). During a mean follow-up of 5,53 ± 2,48 years 32% of women and 42% of men died. Kaplan-Meier curve depicted a significantly lower mortality for women than for men (p = 0,05). The median survival time was 6,73 years (55 deaths per 1000 person-years) versus 6,37 years (78 deaths per 1000 person-years) for women and men, respectively. Conclusions In agreement with previous studies, our data indicate that primary prevention implantation rates for dilated cardiomyopathy are lower in women. However, the reasons are not entirely understood.

Clinical significance of precedent asymptomatic non-sustained ventricular tachycardias on subsequent ICD interventions and heart failure hospitalization in primary prevention ICD patients

BackgroundThe prognostic implications of non-sustained ventricular tachycardia (NSVT) and their significance as therapeutic targets in patients without prior sustained ventricular arrhythmias remain undetermined. The aim of this study was to investigate the prognostic significance of asymptomatic NSVT in patients who had primary prevention implantable cardioverter-defibrillator (ICD) implantation due to ischemic or non-ischemic cardiomyopathy (ICM, NICM).MethodsWe enrolled 157 consecutive primary prevention ICD patients without previous appropriate ICD therapy (AIT). Patients were allocated to two groups depending on the presence or absence of NSVT in a 6-month period prior to enrollment. The incidence of AIT and unplanned hospitalization due to decompensated heart failure (HF) were assessed during follow-up.ResultsIn 51 patients (32%), precedent NSVT was documented. During a median follow-up of 1011 days, AIT occurred in 36 patients (23%) and unplanned HF hospitalization was observed in 32 patients (20%). In precedent NSVT patients, the incidence of AIT and unplanned HF hospitalization was significantly higher as compared to patients without precedent NSVT (AIT: 29/51 [57%] vs. 7/106 [7%], P < 0.001, log-rank; HF hospitalization: 16/51 [31%] vs. 16/106 [15%], P = 0.043, log-rank). Cox-regression demonstrated that precedent NSVT independently predicted AIT (P < 0.0001). In subgroup analyses, precedent NSVT predicted AIT in both ICM and NICM (P < 0.0001, P = 0.020), but predicted HF hospitalization only in patients with ICM (P = 0.0030).ConclusionsPrecedent non-sustained VT in patients with primary prevention ICDs is associated with subsequent appropriate ICD therapies, and is an independent predictor of unplanned heart failure hospitalizations in patients with ischemic cardiomyopathy.

P181 Implantable cardioverter defibrillator and cardiac resynchronisation therapy use in New Zealand

Abstract Introduction The ANZACS-QI DEVICE registry is a national registry designed to collect data on all cardiac implantable electronic devices (CIED) implanted in New Zealand (NZ). This study aims to provide a contemporary analysis of the clinical characteristics and implant details of patients receiving implantable cardioverter defibrillator (ICD) and cardiac resynchronisation therapy (CRT), including CRT-Pacemaker (CRT-P) and CRT-Defibrillator (CRT-D). Methods Complete datasets of ICD, CRT-D and CRT-P implants from the ANZACS-QI DEVICE registry from 1st January 2014 to 31st December 2017 were analysed. Results A total of 1579 ICD implants were identified. Of the 1152 (73.0%) new implants, 565 (49.0%) were for primary prevention and 587 (51.0%) were for secondary prevention. The baseline demographics of both groups were similar, with a median age of 62 and predominantly male (79.2-81.4%), with European (63.7-66.8%) and Maori (21.1-24.8%) being the most common ethnicities. The mean BMI was 29.6-30.2 kg/m², with most patients (75.2-80.7%) being in sinus rhythm at the time of ICD implant. Compared to the secondary prevention group, the primary prevention group had more patients with a history of heart failure (80.4% vs 39.7%), worse heart failure symptoms (NYHA Class II-III 77.1% vs 47.3%), poorer left ventricular ejection fraction (LVEF) (mean 25.1% vs 30.3%) and the aetiology was more likely to be non-ischaemic (57.5% vs 44.2%). The mean QRS duration was longer (129.9ms vs 113.4ms), with a higher incidence of left bundle branch block (31.9% vs 16.0%) and a correspondingly higher rate of CRT-D implants (27.4% vs 8.3%). In the 427 (27.0%) ICD replacements, over a mean duration of 6.27 years, 46.6% had delivered appropriate therapy (including 38.4% with appropriate ICD shocks) whilst 17.8% had delivered inappropriate therapy. Compared to primary prevention CRT-D (n = 155), patients receiving CRT-P (n = 175) were older (median age 74 vs 66) and more likely to be female (38.3% vs 19.4%). CRT-D patients had longer mean QRS duration (169.2ms vs 160.8ms) and poorer LVEF (mean 24.3% vs 28.7%). Conclusion This analysis provides contemporary data on ICD and CRT use in New Zealand. Primary prevention ICD patients were more likely to have a history of heart failure, worse heart failure symptoms, more prolonged QRS duration, left bundle branch block and poorer LV function compared to secondary prevention ICD. Compared to primary prevention CRT-D, patients receiving CRT-P were older and more likely to be female.

The Benefit of Prophylactic Implantable Cardioverter Defibrillator Implantation in Asymptomatic Heart Failure Patients With a Reduced Ejection Fraction

Recommendations for prophylactic implantable cardioverter defibrillator (ICD) implantation in asymptomatic heart failure patients with a reduced left ventricular ejection fraction (LVEF) differ between guidelines. Evidence on the risk of appropriate device therapy (ADT) and death in New York Heart Association (NYHA) class I patients is scarce. Aim of this study is to evaluate ADT and mortality in NYHA-I primary prevention ICD patients with a LVEF ≤35%. A retrospective cohort was studied, including 572 patients with LVEF ≤35% who received a prophylactic ICD with or without resynchronization therapy (CRT-D). To evaluate the incidence of ADT and mortality, NYHA-I was compared with NYHA-II-III using Cox regression analysis. During a follow-up of 4.1 ± 2.4 years, 33% of the NYHA-I patients received ADT compared with 20% of the NYHA-II-III patients (hazard ratio 1.5, 95% confidence interval 1.04 to 2.31, p = 0.03). No differences in mortality were observed (hazard ratio 0.70, 95% confidence interval 0.49 to 1.07, p = 0.10). Additional analyses showed no difference in time to ADT excluding CRT patients (ICD-NYHA-I patients vs ICD-NYHA-II-III patients, p = 0.17) and comparing ischemic and nonischemic cardiomyopathy NYHA-I patients (p = 0.13). Multivariable Cox regression analyses showed that NYHA class was the strongest independent predictor of ADT. In conclusion, primary prevention NYHA-I ICD patients showed a higher incidence of ADT compared with NYHA-II-III ICD patients. These results strongly suggest that primary prevention NYHA-I patients with a LVEF ≤35% are likely to benefit from ICD therapy and should not be excluded from a potentially life-saving therapy.

Rate of Appropriate and Inappropriate Therapy in Patients with Non-Ischaemic Cardiomyopathy, A Comparison between Primary and Secondary Prevention Implantable Cardioverter-Defibrillator Patients

Implantable cardioverter defibrillators (ICDs) have demonstrated favourable outcomes on survival in selected patients with cardiomyopathy. However, recent studies have questioned the protective role of ICD in Non-ischaemic Cardiomyopathy (NICM) for primary prevention. Aim: To investigate the differences in ICD therapy in primary and secondary prevention ICD patients. Between 2014–2017, 182 patients (male = 117; age = 63 ± 17 years, female = 65; age = 63 ± 17 years) had ICD for NICM. Patients were divided into primary prevention (n = 97) and secondary prevention groups (n = 85) based on implant indication. Patients’ Left Ventricular Ejection Fractions (LVEF) were determined by transthoracic echocardiogram. ICD stored data of ICM and NICM patients were utilised. Cumulative first shock rate, type and appropriateness of therapy were determined. There was no significant difference in clinical characteristics between the primary prevention group and secondary prevention group. Mean follow-up was 30 months after implantation. Overall ICD therapy rate was 19%. Cumulative probability of a first appropriate shock was higher in the secondary prevention group (p = 0.03). Overall, ICD therapy was significantly more frequent in the secondary prevention vs primary prevention group (25% vs 13%, p = 0.02). Inappropriate device therapy rate was insignificantly higher in primary prevention group (23% vs 19% p = NS). The rate of appropriate device therapy was significantly greater in secondary prevention group. Inappropriate device therapy was significantly high in both groups. Due to the inherent risks associated with ICD implantation, generator changes and inappropriate therapy, further risk stratification is required for risk of SCD.

Clinical outcome in patients with implantable cardioverter-defibrillator and cancer: a nationwide study.

Patients with cancer are insufficiently represented in randomized clinical trials investigating efficacy of implantable cardioverter-defibrillators (ICDs). We aimed to describe outcomes in patients with a pre-existing diagnosis of cancer at time of ICD implantation. We utilized Danish nationwide registries to identify primary and secondary prevention ICD implantations from 2007 to 2012. Multivariable Cox models were used to assess the risk of appropriate ICD therapy and mortality in patients with and without cancer at time of implantation. During a median follow-up of 2.1 years, 2935 primary prevention ICD and 2730 secondary prevention ICD implantations were identified. Out of these [289 (5.1%)] had pre-existing cancer [primary 140 (4.8%), secondary 149 (5.5%)]. No differential risk for appropriate ICD therapy was found between patients with or without cancer, [primary cancer: 19/140, no cancer: 380/2795, hazard ratio (HR) = 1.07 (0.67-1.69)] and [secondary cancer: 42/149, no cancer: 699/2581, HR = 1.28 (0.93-1.75)]. In primary patients, cancer was not associated with higher risk of 1-year [cancer: 10/140, no cancer: 133/2795, HR = 1.20 (0.84-2.28)] or all-time mortality [cancer: 22/140, no cancer: 339/2795, HR = 1.13 (0.74-1.75)]. In secondary patients, cancer was associated with a higher 1-year [cancer: 19/149, no cancer: 108/2581, HR = 2.62 (1.60-4.29)] and all-time mortality [cancer: 44/149, no cancer: 315/2581, HR = 2.36 (1.71-3.24)]. Implantable cardioverter-defibrillators were implanted in a minority of cancer patients. No difference in risk of appropriate therapy was observed between cancer and non-cancer patients, regardless of implant indication. Cancer was associated with increased mortality in secondary prevention ICD patients, but not in primary prevention ICD patients. In secondary prevention ICD patients, the majority of deaths were attributable to cancer.

Left Ventricular Entropy Is a Novel Predictor of Arrhythmic Events in Patients With Dilated Cardiomyopathy Receiving Defibrillators for Primary Prevention

ObjectivesThe aim of this study was to assess the utility of left ventricular (LV) entropy, a novel measure of myocardial heterogeneity, for predicting cardiovascular events in patients with dilated cardiomyopathy (DCM). BackgroundCurrent risk stratification for ventricular arrhythmia in patients with DCM is imprecise. LV entropy is a measure of myocardial heterogeneity derived from cardiac magnetic resonance imaging that assesses the probability distribution of pixel signal intensities in the LV myocardium. MethodsA registry-based cohort of primary prevention implantable cardioverter-defibrillator patients with DCM had their LV entropy, late gadolinium enhancement (LGE) presence, and LGE mass measured on cardiac magnetic resonance imaging. Patients were followed from implantable cardioverter-defibrillator placement for arrhythmic events (appropriate implantable cardioverter-defibrillator therapy, ventricular arrhythmia, or sudden cardiac death), end-stage heart failure events (cardiac death, transplantation, or ventricular assist device placement), and all-cause mortality. ResultsOne hundred thirty patients (mean age 55 years, 83% men, LV ejection fraction 29%, mean LV entropy 5.58 ± 0.72, LGE present in 57%) were followed for a median of 3.2 years. Eighteen (14.0%) experienced arrhythmic events, 17 (13.1%) experienced end-stage heart failure events, and 7 (5.4%) died. LV entropy provided substantial improvement of predictive ability when added to a model containing clinical variables and LGE mass (hazard ratio: 3.5; 95% confidence interval: 1.42 to 8.82; p = 0.007; net reclassification index = 0.345, p = 0.04). For end-stage heart failure events, LV entropy did not improve the model containing clinical variables and LGE mass (hazard ratio: 2.03; 95% confidence interval: 0.78 to 5.28; p = 0.14). Automated LV entropy measurement has excellent intraobserver (mean difference 0.04) and interobserver (mean difference 0.03) agreement. ConclusionsAutomated LV entropy measurement is a novel marker for risk stratification toward ventricular arrhythmia in patients with DCM.

Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study

There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94). In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

The relationship between baseline and follow-up left ventricular ejection fraction with adverse events among primary prevention ICD patients

BackgroundLeft ventricular ejection fraction (LVEF) is used to select patients for primary prevention implantable cardioverter defibrillators (ICDs). The relationship between baseline and long-term follow-up LVEF and clinical outcomes among primary prevention ICD patients remains unclear. MethodsWe studied 195 patients with a baseline LVEF ≤35% ≤6 months prior to ICD implantation and follow-up LVEF 1–3 years after ICD implantation without intervening left ventricular assist device (LVAD) or transplant. The co-primary study endpoints were: (1) a composite of time to death, LVAD, or transplant and (2) appropriate ICD therapy. We examined multivariable Cox proportional hazard models with a 3-year post-implant landmark view; the LVEF closest to the 3-year mark was considered the follow-up LVEF for analyses. Follow-up LVEF was examined using 2 definitions: (1) ≥10% improvement compared to baseline or (2) actual value of ≥40%. ResultsFifty patients (26%) had a LVEF improvement of ≥10% and 44 (23%) had a follow-up LVEF ≥40%. Neither baseline nor follow-up LVEF was significantly associated with the composite endpoint. In contrast, both baseline and follow-up LVEF were associated with risk for long-term ICD therapies, whether follow-up LVEF was modeled as a ≥10% absolute improvement (baseline LVEF HR 0.87, CI 0.91–0.93, P < .001; follow-up LVEF HR 0.18, CI 0.06–0.53, P = .002) or a ≥40% follow-up value (baseline LVEF HR 0.89, CI 0.83–0.96, P = .001, follow-up LVEF HR 0.26, CI 0.08–0.87, P = .03). ConclusionsAmong primary prevention ICD recipients, both baseline and follow-up LVEF were independently associated with long-term risk for appropriate ICD therapy, but they were not associated with time to the composite of LVAD, transplant, or death.

Improving sudden cardiac death risk stratification by evaluating electrocardiographic measures of global electrical heterogeneity and clinical outcomes among patients with implantable cardioverter-defibrillators: rationale and design for a retrospective, multicenter, cohort study.

Implantable cardioverter-defibrillators (ICDs) improve survival of systolic heart failure (HF) patients who are at risk of sudden cardiac death (SCD). We recently showed that electrocardiographic (ECG) global electrical heterogeneity (GEH) is independently associated with SCD in the community-dwelling cohort and developed GEH SCD risk score. The Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study is a retrospective multicenter cohort designed with two goals: (1) validate an independent association of ECG GEH with sustained ventricular tachyarrhythmias and appropriate ICD therapies and (2) validate GEH ECG risk score for prediction of sustained ventricular tachyarrhythmias and appropriate ICD therapies in systolic HF patients with primary prevention ICD. All records of primary prevention ICD recipients with available data for analysis are eligible for inclusion. Records of ICD implantation in patients with inherited channelopathies and cardiomyopathies are excluded. Raw digital 12-lead pre-implant ECGs will be used to measure GEH (spatial QRST angle, spatial ventricular gradient magnitude, azimuth, and elevation, and sum absolute QRST integral). The primary endpoint is defined as a sustained ventricular tachyarrhythmia event with appropriate ICD therapy. All-cause death without preceding sustained ventricular tachyarrhythmia with appropriate ICD therapy will serve as a primary competing outcome. The study will draw data from the academic medical centers. We describe the study protocol of the first multicenter retrospective cohort of primary prevention ICD patients with recorded at baseline digital 12-lead ECG. Findings from this study will inform future trials to identify patients who are most likely to benefit from primary prevention ICD. URL: http://www.clinicaltrials.gov . Unique identifier: NCT03210883.

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): registry design and baseline characteristics of aprospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator.

BackgroundImplantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy.Methods/designThe DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up is once a year. At baseline, the mean age was 66 (standard deviation [SD] 10) years and 27% were women.ConclusionThe DO-IT Registry represents a real-world nationwide cohort of patients receiving ICDs for primary prevention of sudden cardiac death with reduced left ventricular function in a setting of structural heart disease. The registry investigates the efficacy of the current practice and aims to develop prediction rules to identify subgroups who will not (sufficiently) benefit from ICD implantation and to provide results regarding costs and budget impact of targeted supply of primary preventions ICDs.Electronic supplementary materialThe online version of this article (doi: 10.1007/s12471-017-1016-x) contains supplementary material, which is available to authorized users.

The use of guideline recommended beta-blocker therapy in primary prevention implantable cardioverter defibrillator patients: insight from Danish nationwide registers.

We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. From the Danish Pacemaker and ICD Registry we identified all 1st-time primary prevention ICD and cardiac resynchronization therapy defibrillator (CRT-D) implantations in Denmark from 2007-12 (n = 2935). Use of beta-blocker, type and dose was acquired through the Danish Prescription Registry. According to guideline recommendations, we defined target daily doses as ≥50 mg carvedilol and ≥200 mg metoprolol. Prior to implantation 2427 of 2935 (83%) patients received beta-blocker therapy, with 2166 patients (89%) having initiated treatment 3 months or more prior to implantation. The majority of patients was prescribed carvedilol (52%) or metoprolol (41%). Patients on carvedilol reached target dosages more frequently than patients on metoprolol, with 39% of patients on carvedilol and 26% of patients on metoprolol at the time of implantation (P < 0.001 for all time-points). Increase in proportion of patients reaching target daily doses was observed for both carvedilol and metoprolol after ICD implantation. Carvedilol treatment was a strong predictor for being on target dose of BB at time of implant, as was treatment with angiotensin-converting enzyme inhibitors and/or spironolactone, no history of myocardial infarction, younger age and less pronounced heart failure symptoms. In a real-life setting of primary prevention ICD patients, 39% and 26% of patients were titrated to optimal target dose of carvedilol or metoprolol prior to implantation. A higher proportion of patients on carvedilol reached target dose, as compared with metoprolol.

Extended detection time to reduce shocks is safe in secondary prevention patients: The secondary prevention substudy of PainFree SST

Prolonged ventricular fibrillation (VF) detection has been shown to reduce implantable cardioverter-defibrillator (ICD) therapies and improve prognosis in primary prevention ICD patients. Data in secondary prevention patients are limited. The PainFree SST secondary prevention study is the largest trial of secondary prevention patients randomized between standard and prolonged detection to assess the safety of this strategy in these patients. A total of 705 secondary prevention patients implanted with an ICD in the PainFree SST trial were enrolled in this substudy; 353 patients were randomized to VF detection of 18/24 intervals and 352 patients to 30/40. All other VF parameters were standardized by protocol. The 1-year arrhythmic syncope-free rates in the standard and prolonged groups were 97.7% vs 96.9%, respectively, (P = .0034 for noninferiority). Freedom from all-cause syncope was 96% in both arms (P = .0013 for noninferiority). There was no difference in the time to first appropriate or inappropriate VF therapy. However, the rates of treated VF episodes were lower in the prolonged arm (1.48 per patient per year vs 0.44 per patient per year, P = .0001). A trend toward lower mortality in the prolonged group was not statistically different (5.6% 1 year, 12% 2 years vs 3.8% 1 year, 7.7% 2 years, adjusted hazard ratio = 0.60, P = .061). This large prospective randomized study shows that prolonged detection can safely be programmed in secondary prevention ICD patients with new or existing devices. This programming strategy decreases the rate of treated events and is not associated with an increased risk of syncope or mortality.

Abstract 16940: Serum Amine-based Metabolites and Their Association With Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients

Background: 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. Objective: 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). Methods and Results: Baseline serum was quantitatively profiled for 42 known biologically-relevant amine-based metabolites among 402 patients from the PROSE-ICD Study (derivation group) and 240 patients from the GRADE Study (validation group) for ventricular arrhythmia-induced ICD shocks and all-cause mortality. In multivariate Cox models adjusted for traditional cardiovascular risk factors, 3 amines (N-methyl-L-histidine, symmetric dimethylarginine [SDMA], and L-kynurenine) were associated with all-cause mortality in both derivation and validation cohorts (Figure 1). Additionally, L-histidine, SDMA, L-kynurenine, L-4-hydroxyproline, and L-glutamine were associated with ventricular arrhythmia-induced ICD shocks in one of the cohorts, suggesting their potential to be novel markers of ventricular arrhythmia (Figure 2). Conclusions: Utilizing metabolic profiling, we identified several novel amine markers that were associated with appropriate shock and mortality in primary prevention ICD patients. These findings shed insight into the potential biologic pathways leading to adverse events in these patients, which will in turn aid the development of newer therapeutics for reducing SCD and mortality.

Abstract 16941: Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter Defibrillators (ICDs): Insights From the Cardiovascular Research Network Longitudinal Study of ICDs

Introduction: Primary prevention implantable cardioverter defibrillators (ICDs) reduce mortality in select patients with left ventricular systolic dysfunction (LVSD). The occurrence of device therapies after ICD implantation in contemporary clinical practice is not well described, especially in patient subgroups designated in the Centers for Medicare and Medicaid Services (CMS) 2005 Coverage with Evidence Development (CED). Methods: The Longitudinal Study of ICDs assessed rates and correlates of device therapies (overall and those requiring shock) up to 3 years post-implant among 2540 patients with LVSD receiving first-time primary prevention ICDs in 7 US health care systems from 2006-2009. Implant data from the National Cardiovascular Data Registry ICD Registry were linked to electronic longitudinal health care system data and a novel centrally adjudicated repository of device therapies abstracted from medical records. Proportional hazard models evaluated associations with device therapies by appropriateness, adjusted for demographic and clinical factors. Results: Subjects were 26% women, 35% &lt;65 years old, and 59% non-Hispanic white. Over a mean 26 months, 738 (29.1%) received at least 1 therapy (median 2). Estimated 3-year risk of any device therapy was 36% (24% appropriate, 12% inappropriate); for therapy requiring shock, corresponding values were 24%, 14%, 9%. The rate of appropriate therapy was higher in men than women (adjusted hazard ratio 1.84, 95% confidence interval 1.43-2.35). The rate of inappropriate therapy was higher for subjects &lt;65 than for those &gt;=65 years (1.40, 1.04-1.88), and lower among 2009 implants compared to 2006 (0.66, 0.46-0.95). Regarding the 3 CMS CED patient subgroups, neither ejection fraction nor heart failure symptom severity was associated with device therapy; for LVSD etiology, the rate of inappropriate therapy was nominally but not significantly higher among subjects with non-ischemic cardiomyopathy of &lt; 9 months duration (1.38, 0.88-2.18). Conclusions: In a representative cohort of primary prevention ICD patients in usual care, rates of device therapies were somewhat lower than in landmark trials, differed by some patient characteristics, but did not differ meaningfully for CMS CED subgroups.