Efficacy Of Implantable Cardioverter-defibrillator Research Articles

Comparison of outcomes and required tools between transvenous extraction of pacemaker and implantable cardioverter defibrillator leads: Insight from single high-volume center experience.

Reports of comparison with procedural outcomes for implantable cardioverter defibrillator (ICD) and pacemaker (PM) transvenous lead extraction (TLE) are old and limited. We sought to compare the safety, efficacy, and procedural properties of ICD and PM TLE and assess the impact of lead age. The study cohort included all consecutive patients with ICD and PM TLE in the Cleveland Clinic Prospective TLE Registry between 2013 and 2022. Extraction success, complications, and failure employed the definitions described in the HRS 2017 TLE guidelines. A total of 885 ICD leads, a median implant duration of 8 (5-11) years in 810 patients, and 1352 PM leads of 7 (3-13) years in 807 patients were included. Procedural success rates in ICD patients were superior to those of PM in >20 years leads but similar in ≤20 years leads. In the PM group, the complete success rate of TLE decreased significantly according to the increase of lead age, but not in the ICD group. ICD TLE required more extraction tools compared with PM TLE but cases with older leads required non-laser sheath extraction tools in both groups. The most common injury site in major complication cases differed between ICD and PM TLE, although major complication rates showed no difference in both groups (2.7% vs. 1.6%, p = .12). The procedural success rate by TLE is greater for ICD patients than PM patients with leads >20 years old but requires more extraction tools. Common vascular complication sites and the impact of lead age on procedural outcomes and required tools differed between ICD and PM TLE.

Efficacy of ICD in ischemic cardiac disease determined by reconstructing patient-level data from Kaplan-Meier survival curves

Background: Implantable cardioverter defibrillators (ICDs) are indicated for the prevention of sudden death in ischemic heart disease. Four randomized trials are the main source of efficacy data. Aims and Methods: Reconstruction of patient-level data from survival curves is a new technique (called the Shiny method or IPDfromKM method) for studying effectiveness. We used this method to analyze the four afore-mentioned trials based on the endpoint of all-cause mortality. After reconstruction by the IPDfromKM method, patient-level data were pooled according to three therapeutic options: ICDs, medical therapy, and no active treatment. Standard statistical comparisons were then made between these three groups of patients. Time-to-event data for reconstructed patients were evaluated using standard Kaplan-Meier analysis. The hazard ratio was estimated to compare and interpret these survival data. Results: A total of 4,621 patients were enrolled (follow-up, 60 months). Of these, 1,827 were treated with ICDs and 1,493 received medical therapy; the control group included 1,301 patients who received no active treatment. Our analysis, based on pooled Kaplan-Meier curves, showed that ICD was the most effective, followed by medical therapy and no active treatment. ICD was associated with significantly better survival compared with medical therapy (hazard ratio, 0.6523; 95% confidence interval [CI], 0.5580 to 0.7622; p<0.001) and no active treatment (hazard ratio, 0.6340; 95%CI, 0.5417 to 0.7424; p<0.001). In the subgroup of patients receiving an ICD, the heterogeneity between trials was negligible, whereas it was significant in the subgroups receiving medical therapy or no active treatment. Conclusions: Our results provide original evidence on long-term survival in ischemic heart disease. Methodologically, our study confirmed the advantages of the Shiny method.

Two-Year Outcomes of Primary Prophylactic Use of Defibrillators for Ischemic and Non-Ischemic Cardiomyopathy - Propensity Score-Matched Analysis From the Nippon Storm Study.

In 2016, the DANISH study reported negative results regarding the efficacy of implantable cardioverter-defibrillators (ICDs) in patients with non-ischemic cardiomyopathy (NICM) and reduced left ventricular ejection fraction (LVEF). In this study we determined the efficacy of using ICDs for primary prophylaxis in patients with NICM.Methods and Results: We selected 1,274 patients with underlying cardiac disease who were enrolled in the Nippon Storm Study. We analyzed the data of 451 patients with LVEF ≤35% due to NICM or ischemic cardiomyopathy (ICM) who underwent ICD implantation for primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ICM, 33%). After propensity score matching, we compared the baseline covariates between groups: NICM (132 patients) and ICM (132 patients). The 2-year appropriate ICD therapy risks were 27.7% and 12.2% in the NICM and ICM groups, respectively (hazard ratio, 0.390 [95% confidence interval, 0.218-0.701]; P=0.002). This subanalysis of propensity score-matched patients from the Nippon Storm Study revealed that the risk of appropriate ICD therapy was significantly higher in patients with NICM than in those with ICM.

Effect of implantable cardioverter-defibrillator in non-ischaemic systolic heart failure according to the Heart Failure Collaboratory Medical Therapy Score: extended follow-up of the DANISH trial

Abstract Background The Heart Failure Collaboratory (HFC) has developed a medical therapy score which integrates types and doses of guideline-directed pharmacotherapies in patients with systolic heart failure, providing a measure of treatment quality. In clinical trials, this score may help determine the additive effect of new treatments. In the Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICDs) in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. Purpose Adding four years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to baseline modified HFC (mHFC) medical therapy score. Methods In the DANISH trial, 1,116 patients with non-ischaemic systolic heart failure were randomised to receive an ICD (N = 556) or usual clinical care (N = 560, control group). The primary outcome was death from any cause. In the mHFC score, patients were assigned a score for each drug class of the original cornerstones of systolic heart failure treatment (renin-angiotensin-system inhibitor, beta-blocker, and mineralocorticoid receptor antagonist). The maximum score was 100%, corresponding to optimal medical therapy with all three types of medication (=>50% of target dose). Results The median mHFC score at baseline was 67% (25th-75th percentile, 67%-100%; range, 17%-100%). During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74-1.08]). The results were independent of the mHFC score at baseline (mHFC score = < median: HR 0.91 [95% CI, 0.70-1.19]; mHFC score > median: HR 0.87 [95% CI, 0.66-1.14]; P for interaction, 0.94). Similarly, ICD implantation did not reduce the rate of cardiovascular death overall (HR 0.87 [95% CI, 0.70-1.09]), and this association was not modified by the mHFC score (mHFC score = < median: HR 0.90 [95% CI, 0.65-1.24]; mHFC score > median: HR 0.84 [95% CI, 0.61-1.15]; P for interaction, 0.89). The ICD group had a significantly lower rate of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40-0.92]), and this association was not modified by the mHFC score (mHFC score = < median: HR 0.72 [95% CI, 0.40-1.29]; mHFC score > median: HR 0.53 [95% CI, 0.28-0.99]; P for interaction, 0.59). See Figure for results. Conclusions In this extended follow-up study of the DANISH trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure regardless of baseline medical heart failure therapy, assessed by the mHFC score.Modified HFC score in the DANISH trial

Effect of ICD on patients with improved EF in idiopathic dilated cardiomyopathy

Abstract Background The efficacy of implantable cardioverter defibrillator (ICD) therapy in patients who had heart failure with improved ejection fraction (HFimpEF) above guidelines indication for ICD (>35%) during generator change is still controversial. This meta-analysis assesses the impact of ICD therapy in patients with HFimpEF with EF >35% and patient with NICM. Methods Databases were searched for studies reporting the association between ICD in patients with NICM and HFimpEF and ventricular arrhythmias (VA) and sudden cardiac death (SCD); including Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimal follow up duration was one year. Results A total of 38 studies and 13,538 patients (5,829 with improved EF vs 7,709 with EF <35% during follow up) were included; mean follow up was 43 months (ranging between 12 to 74 months). Mean age was 63.5 and 75% were males. Patients with HFimpEF with ICD, wither alone or as part of CRT therapy, was associated with lower risk of VA and SCD (OR 0.39, 95% CI 0.32-0.47; P<0.01; annual rate 4.1 vs. 8%). Sub-analysis for patients with ICD for patient with NICM was associated with lower risk of VA and SCD (OR 0.25, 95% CI 0.1-0.62; P<0.01; annual rate 2.9 vs. 10.2%). (Figure) Conclusion Improved EF is associated with reduced VA but with still elevated risk in HFimpEF especially in NICM.

Efficacy of implantable cardioverter-defibrillator in non-ischemic systolic heart failure in patients with and without chronic kidney disease: an extended follow-up analysis of the DANISH trial

Abstract Background Patients with heart failure (HF) and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter defibrillators (ICDs). Purpose In this extended follow-up study of the Danish Study to Assess the Efficacy of primary prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart failure on Mortality (DANISH), adding four years of additional follow-up, we examined the long-term effects of primary-prevention ICD implantation, compared with usual medical care, according to baseline CKD status. Methods In the DANISH trial, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (eGFR ≥/< 60 mL/min/1.73 m2) at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death. Results In total, 1,113 patients had an available eGFR measurement at baseline (median eGFR 73 ml/min/1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual medical care, did not reduce the rate of death from any cause (no CKD, HR 0.81 [95% CI, 0.64-1.03]; CKD, HR 0.92 [0.68-1.26]; P for interaction=0.31) or cardiovascular death (no CKD, HR 0.76 [0.57-1.02]; CKD, HR 0.95 [0.66-1.36]; P for interaction=0.21), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR 0.57 [0.32-1.00]; CKD, HR 0.60 [0.31-1.14]; P for interaction=0.70). Conclusions Primary-prevention ICD implantation did not provide an overall survival benefit regardless of baseline kidney function in patients with non-ischemic systolic heart failure.Figure

Two-year outcomes of primary prophylactic use of defibrillators with ischemic and non-ischemic cardiomyopathy: propensity score-matched analysis from NIPPON STORM Study

Abstract Background In 2016, the DANISH study showed negative results regarding the efficacy of implantable cardioverter defibrillators (ICDs) for patients with non-ischemic cardiomyopathy (NICM) and reduced left ventricular ejection fraction (LVEF). Thus, the ESC guidelines downgraded the indication for primary ICD prophylaxis for NICM patients with reduced LVEF from Class I to IIa. However, the change might be felt somewhat improper in the real wolrd ICD therapy and decided to use the Nippon storm study, a prospective registry study in Japan, to determine whether the DANISH results are of equal value in the clinical setting. Objective To determine the efficacy of ICDs as primary prevention in patients with NICM, the incidence of ICD appropriate therapy in patients with NICM was compared with that in patients with ischemic cardiomyopathy (ICM) for which primary ICD efficacy is generally recognized as a Class I indication. Methods We selected 1274 patients with underlying cardiac disease from a total of 1548 patients enrolled in the Nippon storm study. We analyzed data of 451 patients with LVEF ≤35% owing to NICM or ICM who underwent ICD implantation of primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±1.4%; cardiac resynchronization therapy, 20%; ICM, 33%). All patients were followed up for at least 2 years. Patient selection was performed by employing the propensity score matching method with a digit-matching algorithm for clinical factors, ie, age, sex, cardiac resynchronization therapy with a defibrillator, LVEF. After all propensity score matches had been performed, we compared baseline covariates between the 2 groups: 132 patients with NICM and 132 with ICM. The cumulative incidences of ICD therapies (including both anti-tachycardia pacing and shock therapies) were calculated using competing risk analysis, because death is a competing risk for loss to follow-up. Results In the matched cohort, the 2-year appropriate ICD therapy risks were 27.7% and 12.2% in NICM and ICM groups, respectively (HR = 0.390 [95% CI, 0.218–0.701; P = 0.002) (Figure A). Two-year appropriate ATP therapy risks were 25.5% and 11.4% in NICM and ICM groups, respectively (HR = 0.417 [95% CI, 0.226– 0.776; P = .005]) (Figure B), and appropriate shock therapy risks were 6.3% and 1.6% in NICM and ICM groups, respectively (HR = 0.230 [95% CI, 0.049–1.085; P = .063]) (Figure C). Conclusion The present subanalysis of the Nippon Storm Study revealed that the risk for appropriate ICD therapy was significantly higher in the patients with NICM than in those with ICM based on our propensity score–matching method.

The Uncertain Benefit from Implantable Cardioverter-Defibrillators in Nonischemic Cardiomyopathy: How to Guide Clinical Decision-Making?

Life-threatening dysrhythmias remain a significant cause of mortality in patients with nonischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillators (ICD) effectively reduce mortality in patients who have survived a life-threatening arrhythmic event. The evidence for survival benefit of primary prevention ICD for patients with high-risk NICM on guideline-directed medical therapy is not as robust, with efficacy questioned by recent studies. In this review, we summarize the data on the risk of life-threatening arrhythmias in NICM, the recommendations, and the evidence supporting the efficacy of primary prevention ICD, and highlight tools that may improve the identification of patients who could benefit from primary prevention ICD implantation.

Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure

BackgroundPatients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known. Methods and ResultsIn this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than –20%. The primary end point was all-cause mortality. The median RV-FWS was –18% (quartiles –23% to –14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22). ConclusionsIn patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.

Rationale and design of the Lead Evaluation for Defibrillation and Reliability study: Safety and efficacy of a novel ICD lead design.

Implantable cardioverter defibrillators (ICD) are indicated for primary and secondary prevention of sudden cardiac arrest. Despite enhancements in design and technologies, the ICD lead is the most vulnerable component of the ICD system and failure of ICD leads remains a significant clinical problem. A novel, small-diameter, lumenless, catheter-delivered, defibrillator lead was developed with the aim to improve long-term reliability. The Lead Evaluation for Defibrillation and Reliability (LEADR) study is a multi-center, single-arm, Bayesian, adaptive design, pre-market interventional pivotal clinical study. Up to 60 study sites from around the world will participate in the study. Patients indicated for a de novo ICD will undergo defibrillation testing at implantation and clinical assessments at baseline, implant, pre-hospital discharge, 3 months, 6 months, and every 6 months thereafter until official study closure. Patients may be participating for a minimum of 18 months to approximately 3 years. Fracture-free survival will be evaluated using a Bayesian statistical method that incorporates both virtual patient data (combination of bench testing to failure with in-vivo use condition data) with clinical patients. The clinical subject sample size will be determined using decision rules for number of subject enrollments and follow-up time based upon the observed number of fractures at certain time points in the study. The adaptive study design will therefore result in a minimum of 500 and a maximum of 900 patients enrolled. The LEADR Clinical Study was designed to efficiently provide evidence for short- and long-term safety and efficacy of a novel lead design using Bayesian methods including a novel virtual patient approach.

Efficacy and Safety of an Extravascular Implantable Cardioverter–Defibrillator

BackgroundThe extravascular implantable cardioverter–defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known.MethodsWe conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%.ResultsA total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan–Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period.ConclusionsIn this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.)

Diabetes may modify the efficacy of primary prevention implantable cardioverter-defibrillators in non-ischemic systolic heart failure: an extended follow-up of the DANISH trial

Abstract Background Since patients with both diabetes and heart failure (HF) have a substantially worse prognosis than those with each of these alone, the efficacy of implantable cardioverter defibrillator (ICD) implantation in patients with systolic HF may be modified by diabetes status. Purpose In this extended follow-up analysis of the Danish Study to Assess the Efficacy of primary prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart failure on Mortality (DANISH), adding four years of additional follow-up, we examined the long-term effects of primary prophylactic ICD implantation, compared with usual clinical care, in patients with non-ischemic systolic HF according to diabetes status. Methods In DANISH, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual clinical care (N=550). Outcomes were analyzed according to diabetes status at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death. Results Of the 1,116 patients randomized in DANISH, 211 (18.9%) had diabetes at baseline (median age 64 year-old, 159 males, median left ventricular ejection fraction 25%). There was a statistically significant interaction between diabetes and the effect of ICD implantation on death from any cause and cardiovascular death. There was a trend toward a reduction in both outcomes with ICD implantation, compared with usual clinical care; in patients without diabetes (death from any cause, HR 0.81 [95% CI, 0.65–1.01]; cardiovascular death, HR 0.77 [0.59–1.01]), but not in those with diabetes (death from any cause, HR 1.19 [0.81–1.74]; cardiovascular death, HR 1.20 [0.79–1.82]) (P for interaction = 0.04 and 0.04 for death from any cause and cardiovascular death, respectively). Although there was no statistically significant interaction between diabetes and the effect of ICD implantation on sudden cardiovascular death, ICD implantation significantly reduced the rate of sudden cardiovascular death in patients without diabetes (HR 0.51 [0.31–0.85]), but not in those with diabetes (HR 0.91 [0.41–1.99]) (P for interaction = 0.15). Conclusions In patients with non-ischemic systolic HF, there was a significant interaction between diabetes and the effect of ICD implantation on death from any cause and cardiovascular death, suggesting that individuals without diabetes may derive greater benefit from ICD implantation. Funding Acknowledgement Type of funding sources: None.

The subcutaneous implantable cardioverter-defibrillator should be considered for all patients with an implantable cardioverter-defibrillator indication.

The implantable cardioverter-defibrillator (ICD) is an essential lifesaving device implanted worldwide for the prevention of sudden cardiac death (SCD). Several clinical trials have demonstrated the efficacy of ICDs in both primary and secondary prevention cohorts over the last two and a half decades.1–5 Transvenous implantable cardioverter-defibrillators (TV-ICDs) have traditionally been implanted for such purposes. However, the TV-ICD system has considerable limitations and is associated with short- and long-term adverse events related to the endovascular lead.

Efficacy of Implantable Cardioverter Defibrillator in Nonischemic Systolic Heart Failure According to Sex: Extended Follow-Up Study of the DANISH Trial.

Men and women may respond differently to certain therapies for heart failure with reduced ejection fraction, including implantable cardioverter defibrillators (ICD). In an extended follow-up study of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality), adding 4 years of additional follow-up, we examined the effect of ICD implantation according to sex. In the DANISH trial, 1116 patients with nonischemic systolic heart failure were randomized to receive an ICD (N=556) or usual clinical care (N=550). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 307 (27.5%) were women. During a median follow-up of 9.5 years, women had a lower associated rate of all-cause mortality (hazard ratio [HR], 0.60 [95% CI, 0.47-0.78]) cardiovascular death (HR, 0.62 [95% CI, 0.46-0.84]), nonsudden cardiovascular death (HR, 0.59 [95% CI, 0.42-0.85]), and a numerically lower rate of sudden cardiovascular death (HR, 0.70 [95% CI, 0.40-1.25]), compared with men. Compared with usual clinical care, ICD implantation did not reduce the rate of all-cause mortality, irrespective of sex (men, HR, 0.85 [95% CI, 0.69-1.06]; women, HR, 0.98 [95% CI, 0.64-1.50]; Pinteraction=0.51). In addition, sex did not modify the effect of ICD implantation on sudden cardiovascular death (men, HR, 0.57 [95% CI, 0.36-0.92]; women, HR, 0.68 [95% CI, 0.26-1.77]; Pinteraction=0.76). In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex. URL: https://www. gov; Unique identifier: NCT00542945.

Differences in mode of death between men and women receiving implantable cardioverter-defibrillators or cardiac resynchronization therapy in the MADIT trials

Studies have reported sex differences in outcomes following implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) implantation. However, little is known about sex differences with regard to mode of death or device efficacy following ICD or CRT-D implantation. The purpose of this study was to investigate whether sex influenced mode of death or device efficacy in ICD and CRT-D subjects enrolled in the MADIT (Multicenter Automatic Defibrillator Implantation Trial) studies (MADIT-II, MADIT-CRT, and MADIT-RIT). The combined MADIT cohort consisted of 3038 men and 1000 women with ischemic cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM), left ventricular ejection fraction ≤30%; New York Heart Association functional class I-III heart failure who received ICD or CRT-D. Mode of death was divided into cardiac and noncardiac causes, reviewed by independent adjudication committees. A total of 295 men and 66 women died (9.7% vs 6.6%; P =.003) during 26 months. The most common cause of death was nonarrhythmic cardiac death in men (n = 121 [41%]) and noncardiac death in women (n = 22 [33%]). All-cause mortality and cardiac deaths were 1.5- to 2.0-fold higher in men vs women with ICM but similar for those with NICM after adjustment for covariates. ICD efficacy was similar in men and women, resulting in a 50% reduction in all-cause mortality. CRT-D was more effective at reducing all-cause and cardiac death in women than men. Mode of death differs between sex and is dependent on the underlying cardiac substrate. Compared to women, cardiac death is higher in men with ICM but similar in those with NICM. ICDs are equally effective at reducing mortality in both men and women. However, CRT-D may be more effective at reducing mortality in women.

The cardiac sarcoidosis consortium: elucidating a mysterious disease through collaborative research

Cardiac sarcoidosis (CS) is an inflammatory disease of unknown aetiology that can lead to life-threatening arrhythmias, heart failure, and death. The hallmark pathophysiology involves the development of noncaseating granulomas in cardiac tissue disrupting normal electrical signalling and ultimately impairing cardiac pump function. Advanced cardiac imaging has improved the clinician’s ability to detect the disease, and there has been a significant rise in the number of patients diagnosed with this disorder in the last 20 years. Critical knowledge gaps remain in the domains of aetiology, genetic basis, and immunological mechanisms. There is also uncertainty as to the most appropriate diagnostic criteria, risk stratification, and treatments. The CS literature is mostly comprised of case reports and small retrospective studies; high-quality data from randomized controlled trials are lacking. After collaborating on a multicentre analysis of safety and efficacy of implantable cardioverter defibrillator (ICD) in CS,1 the founding members [Dr Thomas Crawford and Dr Frank Bogun (University of Michigan), Dr William Sauer (then at the University of Colorado), and Dr Kenneth Ellenbogen and Dr Jordana Kron (Virginia Commonwealth University)] established an international, prospective registry, the Cardiac Sarcoidosis Consortium (CSC). The consortium identified five primary aims (Figure 1). The CSC has advocated for inclusion of CS sessions at major national and international meetings and proposed and championed the development of the first CS-specific guidelines, which resulted in the 2014 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated with Cardiac Sarcoidosis.2 Since the inception of the CSC, we have witnessed an increase in academic interest in CS at national meetings and in research publications.

Implantable cardioverter defibrillators in patients with orthotopic heart transplant: A multicenter case series.

Sudden cardiac death (SCD) is common after orthotopic heart transplant (OHT). No clear guidelines for implantable cardioverter defibrillator (ICD) implantation in OHT patients at high risk for SCD currently exist. To assess the safety, efficacy, and benefit of ICDs and resynchronization therapy post-OHT. We also provide a systematic review of previous reports. A retrospective multicenter cohort study within the United States. Patients with ICD post-OHT between 2000 and 2020 were identified. We analyzed 16 patients from 4 centers. The mean standard-deviation (SD) age was 43 (18) years at OHT and 51 (20) years at ICD implantation. The mean (SD) duration from OHT to ICD implantation was 9 (5) years. The mean (SD) left ventricular ejection fraction (LVEF) was 35% (17%). There were 2 (13%) postprocedural complications: 1 hematoma and 1 death. Mean (SD) follow-up was 24 (23) months. Survival rate was 63% (10/16) at 1 year and 56% (9/16) at 2 years, with 6/7 of those who died having LVEF < 35% at the time of the ICD implantation. Patients were more likely to receive appropriate therapy if their ICD was implanted for secondary (5/8) rather than primary (0/8) prevention (p = .007). Of those who did, 4 patients survived to 30 days post-ICD therapy. Severe CAV was not associated with the rate of appropriate therapy. Beneficial outcomes were observed when ICDs were implanted for secondary prevention only, and in patients with higher baseline LVEF. We also observed benefits with resynchronization therapy.

Comorbid Hypertension Reduces the Risk of Ventricular Arrhythmia in Chronic Heart Failure Patients with Implantable Cardioverter-Defibrillators.

Aims: Low blood pressure (BP) has been shown to be associated with increased mortality in patients with chronic heart failure. This study was designed to evaluate the relationships between diagnosed hypertension and the risk of ventricular arrhythmia (VA) and all-cause death in chronic heart failure (CHF) patients with implantable cardioverter-defibrillators (ICD), including those with preserved left ventricular ejection fraction (HFpEF) and indication for ICD secondary prevention. We hypothesized that a stable hypertension status, along with an increasing BP level, is associated with a reduction in the risk of VA in this population, thereby limiting ICD efficacy. Methods: We retrospectively enrolled 964 CHF patients, with hypertension diagnosis and hospitalized BP measurements obtained before ICD implantation. The primary outcome measure was defined as the composite of SCD, appropriate ICD therapy, and sustained VT. The secondary endpoint was time to death or heart transplantation (HTx). We performed multivariable Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances with or without hypertension. The Fine–Gray subdistribution hazard model was used to confirm the results. The effect of random BP measurements on the primary outcome was illustrated in the Cox model with inverse probability weighting. Results: The 964 patients had a mean (SD) age of 58.9 (13.1) years; 762 (79.0%) were men. During the interrogation follow-up [median 2.81 years (interquartile range: 1.32–5.27 years)], 380 patients (39.4%) reached the primary outcome. A total of 244 (45.2%) VA events in non-hypertension patients and 136 (32.1%) in hypertension patients were observed. A total of 202 (21.0%) patients died, and 31 (3.2%) patients underwent heart transplantation (incidence 5.89 per 100 person-years; 95% CI: 5.16–6.70 per 100 person-years) during a median survival follow-up of 4.5 (IQR 2.8–6.8) years. A lower cumulative incidence of VA events was observed in hypertension patients in the initial unadjusted Kaplan–Meier time-to-event analysis [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.53–0.80]. The protective effect was robust after entropy balancing (HR: 0.71, 95% CI: 0.56–0.89) and counting death as a competing risk (HR: 0.71, 95% CI: 0.51–1.00). Hypertension diagnosis did not associate with all-cause mortality in this population. Random systolic blood pressure was negatively associated with VA outcomes (p = 0.065). Conclusions: In hospitalized chronic heart failure patients with implantable cardioverter-defibrillators, the hypertension status and higher systolic blood pressure measurements are independently associated with a lower risk of combined endpoints of ventricular arrhythmia and sudden cardiac death but not with all-cause mortality. Randomized controlled trials are needed to confirm the protective effect of hypertension on ventricular arrhythmia in chronic heart failure patients.

EP News: Clinical

Yafasova et al (Circulation 2022;145:427, PMID 34882430) evaluated long-term follow-up (9.5 years) of 556 patients with nonischemic systolic heart failure randomized to receive an implantable cardioverter-defibrillator (ICD) and 560 to receive usual clinical care in DANISH (The Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality). Overall 208 of 556 patients (37%) in the ICD group and 226 of 560 patients (40%) in the control group died (hazard ratio [HR] 0.89; P = .24).

NT-proBNP and ICD in Nonischemic Systolic Heart Failure: Extended Follow-Up of the DANISH Trial

ObjectivesIn this extended follow-up study of the DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality) trial, adding 4 years of additional follow-up, we examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to baseline N-terminal pro–B-type natriuretic peptide (NT-proBNP) level. BackgroundIn the DANISH trial, NT-proBNP level at baseline appeared to modify the response to ICD implantation. MethodsIn the DANISH trial, 1,116 patients with nonischemic systolic HF were randomized to receive an ICD (N = 556) or usual clinical care (N = 550). Outcomes were analyzed according to NT-proBNP levels (below/above median) at baseline. The primary outcome was death from any cause. ResultsAll 1,116 patients in the DANISH trial had an available NT-proBNP measurement at baseline (median: 1,177 pg/mL; range: 200-22,918 pg/mL). There was a trend toward a reduction in all-cause death with ICD implantation, compared with usual clinical care, in patients with NT-proBNP levels lower than the median (HR: 0.75 [95% CI: 0.55-1.03]), but not in those with higher NT-proBNP levels (HR: 0.95 [95% CI: 0.74-1.21]) (Pinteraction = 0.28). Similarly, ICD implantation significantly reduced the rate of cardiovascular (CV) and sudden cardiovascular death (SCD) in patients with NT-proBNP levels lower than the median (CV death, HR: 0.69 [95% CI: 0.47-1.00]; SCD, HR: 0.37 [95% CI: 0.19-0.75]), but not in those with higher levels (CV death, HR: 0.94 [95% CI: 0.70-1.25]; SCD, HR: 0.86 [95% CI: 0.49-1.51]) (Pinteraction = 0.20 and 0.08 for CV death and SCD, respectively). ConclusionsLower baseline NT-proBNP levels could identify patients with nonischemic systolic HF who may derive benefit from ICD implantation. (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality [DANISH]; NCT00542945)