Implantable Cardioverter-defibrillator Cohort Research Articles

Wearable defibrillator to improve accuracy in selecting candidates to implantable defibrillator: A real-world experience.

The indication for implantable cardioverter defibrillator (ICD) for sudden cardiac death (SCD) prevention relies mostly on left ventricular ejection fraction (LVEF)≤35%. The use of a wearable cardioverter defibrillator (WCD) in the case of dynamic alterations of LVEF may help avoid an improper early ICD implant when a favourable evolution in the post-acute phase is observed and may help reduce costs. This parallel cohort retrospective study included patients with heart failure with reduced ejection fraction (HFrEF) at high risk of arrhythmias recruited in the acute phase and divided into an early ICD cohort and a WCD cohort for primary prevention during the waiting period established by European Society of Cardiology guidelines. A total of 41 consecutive patients were enrolled: 26 in the WCD group and 15 in the early ICD group. Age, LVEF at baseline, causes of HFrEF and drug therapy in the two cohorts were similar. During the waiting period after the inclusion, three patients (11.5%) in the WCD cohort and four (26.7%) in the early ICD cohort developed relevant ventricular arrhythmias (P=0.22); none of them had subsequent LVEF recovery. At the end of the waiting period, 13 patients (50%) in the WCD group and 7 (46.7%) in the early ICD group experienced LVEF recovery (P=0.84). The average cost per patient at the end of the waiting period was €23934 in the early ICD cohort versus €19167 in the WCD cohort (-19.9%). This cost savings from WCD use appears even higher when projected over a 10year period (-41.2%). WCD may represent a cost-effective strategy to more accurately select candidates for the primary prevention ICD implant among high-risk patients with HFrEF. ICD use provides effective protection from SCD and reduces costs compared with an extensive early ICD implant.

Effects of tele-yoga on physical and psychological outcomes in patients living with ICD, a randomised controlled trial

Abstract Background Patients with long-term illness, including those living with an implantable cardioverter defibrillator (ICD), often suffer from symptoms of anxiety and depression, decreased health-related quality-of-life (HRQOL), and impaired functional capacity. Yoga, being a mind-body intervention, may improve all these outcomes. Purpose To determine effects of tele-yoga on exercise capacity and patient-reported outcome measures. Methods A single-blind (evaluator blinded) parallel two-arm RCT with 1:1 distribution. Participants were recruited from four hospitals in Sweden. Inclusion criteria: >18 years, admitted to a cardiology or intensive care units >48 hours during the last 36 months due to ICD implantation or ventricular arrhythmias, heart failure, or conditions in need of intensive care and now clinically stable. The participants were randomised to a control group receiving individual exercise advice or to the intervention group (tele-yoga). The intervention included performing live-streamed group-yoga for 60 min twice/week for 3 months and practicing yoga individually for a minimum of 10 min/day using an app. The group-sessions with approximately 10 participants were led by certified Mediyoga-instructors via the virtual video-platform ZOOM. The yoga form was Kundalini adapted to individuals with health conditions (Mediyoga). Two standardised yoga-programmes including different postures, breathing exercises and meditations were rotated. The primary endpoint of the study after 3 months was a combined endpoint consisting of change in functional capacity measured by 6-min walk test (6MWT), HRQOL (EQ-5D index/VAS) and symptoms of anxiety and depression (HADS). The used cut offs for change were 30 meters for 6MWT, a score >11 for EQ-5D VAS and ≥8 for anxiety/depression in HADS. Secondary endpoints included separate analysis of functional capacity, HRQOL and symptoms of anxiety/depression. Results In total, 311 participants were randomized to tele-yoga (n=156) and control (n=155), mean age 65.8 years, 30% women, 38% living with an ICD (whereof 62% had a primary preventive indication). Median attendance to yoga-sessions was 20 sessions for 12 weeks and 74% of the study participants were adherent to >16 tele-yoga sessions. There were no adverse events reported during yoga sessions or app usage. In this sub-group analysis involving the ICD cohort (n=118), there was a significant improvement in favour of the tele-yoga group in the combined primary endpoint (p=.011). When analysing them separately, there was a significant improvement in 6MWT (p=.002), but not in HRQOL in EQ-5D VAS or symptoms of anxiety and depression. No adverse events were reported during yoga sessions or app usage. Conclusion Digitally delivered mind-body training such as tele-yoga showed a significant improvement in the combined endpoint consisting of physical function, HRQOL and mental health. Tele-yoga may be a promising new form of rehabilitation for patients living with ICD.

Deep embedded clustering of physical behaviour in patients with an implanted cardioverter-defibrillator identifies high and low risk profiles

Abstract Introduction Patients at high risk of sudden cardiac death are treated with an implantable cardioverter-defibrillator (ICD). Patterns in physical behaviour may be prognostic for clinical deterioration. Deep embedded clustering (DEC) employs deep neural networks to learn compact and meaningful representations from high-dimensional data, on which an unsupervised clustering then operates. Purpose The objectives of this study were to use DEC to identify and describe behavioural profiles in a prospective ICD cohort and assess their risk of clinical outcomes. Methods Data from the multicenter, prospective SafeHeart study conducted at our 2 centers, was used. Patients received an implantable cardioverter defibrillator (ICD) between May 2021 and September 2022, who then wore wearable devices during 6 months that capture physical behaviour. Latent representations were extracted from the time-series behavioural data using a variational autoencoder, and used as input to an unsupervised machine learning algorithm (Figure 1). Kaplan-Meier survival curves were used to visualise the annual risk of appropriate ICD-therapy, and the composite of all ICD-therapy and death. Results A total of 272 patients (mean age of 63.1 ±10.2 years, 81% male) were eligible, with a total of 37478 days of behavioural data (138 ±47 days per patient). DEC identified five distinct behavioural profiles: Cluster A (n=70) had high activity levels, mainly at light-to-moderate intensity. Cluster B (n=51) showed above-average sleep efficiency. Cluster C (n=63) exhibited a high-intensity activity profile. Cluster D (n=42) had frequent waking episodes and poor sleep. Cluster E (n=46) had very low physical activity levels and an impaired sleep architecture. Significantly differences were observed between clusters A-E in ICD-therapy and mortality (log-rank p-value 0.04) (Figure 2). Clusters B and D exhibited a threefold decrease in the annual risk of appropriate ICD therapy compared to cluster E. Conclusion DEC reveals distinct behavioural profiles in a prospective ICD cohort, with their inherent risk on outcomes. Wearable accelerometer devices enable behavioural monitoring that may provide opportunities for improved personalised risk prediction in a notoriously heterogeneous high-risk patient population.Deep embedded clustering of behaviourEvent rates stratified for clusters

Abstract 10739: Impact of Cardiac Device Implantation in Elderly Japanese Patients With Heart Failure as Primary Prevention-A Post Hoc Analysis of the HINODE Trial

Introduction: Despite increase in the incidence of chronic heart failure (HF) and sudden cardia death (SCD), the current use of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) in Japan is much lower than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) was designed to prospectively assess the rate of mortality, appropriately treated ventricular arrhythmias (VA) and heart failure (HF) for comparison with references from historical landmark trial MADIT-RIT in Japanese patients. Hypothesis: This sub analysis of HINODE evaluates the impact of ICD or CRT implantation in elderly Japanese patients concomitant with higher risk of heart failure. Methods: After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (1) ICD (2) CRT with defibrillator (CRT-D) (3) standard medical therapy (‘non-device’) (4) pacing (indicated for CRT; received pacemaker or CRT pacing). We compared the all-cause mortality between elderly and non-elderly patients with elderly defined as age>70 at the time of study enrollment. Results: The HINODE study enrolled 354 patients (191 elderly) followed for 19.6 ± 6.5 months with a minimum of 12 months and an absolute death rate of 11.0%. The estimated survival rate for device recipients (n=239) through 24 months was 86.1% (97.5% LCL: 79.8%) with no significant difference for elderly vs non-elderly patients (HR 1.97, 95%CI: 0.86-4.54). Analysis within cohorts showed increased risk of all-cause mortality for elderly with an ICD compared to non-elderly with an ICD (HR 5.09 95% CI: 1.1-23.6). However, ICD cohort excluding those with CRT-D indication showed no significant difference (HR 3.70, 95% CI: 0.75-18.35). No significant difference showed in other cohorts: CRT-D (HR 1.53 95% CI: 0.34-6.84) or pacing (HR 0.84, 95%CI: 0.2-3.5). Ventricular event free rate in ICD and CRT-D patients also had no difference (HR 0.84 95% CI: 0.31-2.25) Conclusions: Although elderly patients might be associated with higher risk of mortality in general, benefit of device therapy is comparable to non-elderly patients. We might consider device therapy despite age as a standalone risk in contemporary Japanese clinical practice.

Implantable cardioverter defibrillator and cardiac resynchronization therapy use in New Zealand (ANZACS-QI 33).

BackgroundThe ANZACS‐QI Cardiac Implanted Device Registry (ANZACS‐QI DEVICE) collects nationwide data on cardiac implantable electronic devices in New Zealand (NZ). We used the registry to describe contemporary NZ use of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT).MethodsAll ICD and CRT Pacemaker implants recorded in ANZACS‐QI DEVICE between 1 January 2014 and 31 December 2017 were analyzed.ResultsOf 1579 ICD implants, 1152 (73.0%) were new implants, including 49.0% for primary prevention and 51.0% for secondary prevention. In both groups, median age was 62 years and patients were predominantly male (81.4% and 79.2%, respectively). Most patients receiving a primary prevention ICD had a history of clinical heart failure (80.4%), NYHA class II‐III symptoms (77.1%) and LVEF ≤35% (96.9%). In the secondary prevention ICD cohort, 88.4% were for sustained ventricular tachycardia or survived cardiac arrest from ventricular arrhythmia. Compared to primary prevention CRT Defibrillators (n = 155), those receiving CRT Pacemakers (n = 175) were older (median age 74 vs 66 years) and more likely to be female (38.3% vs 19.4%). Of the 427 (27.0%) ICD replacements (mean duration 6.3 years), 46.6% had received appropriate device therapy while 17.8% received inappropriate therapy. The ICD implant rate was 119 per million population with regional variation in implant rates, ratio of primary prevention ICD implants, and selection of CRT modality.ConclusionIn contemporary NZ practice three‐quarters of ICD implants were new implants, of which half were for primary prevention. The majority met current guideline indications. Patients receiving CRT pacemaker were older and more likely to be female.

Relative timing of near-field and far-field electrograms can determine the tachyarrhythmia site of origin

Despite improving algorithms, inappropriate shocks for supraventricular tachycardia (SVT) still occur in a significant number of patients with implantable cardioverter-defibrillators (ICDs). This makes the discovery of novel discriminators that use existing ICD hardware an attractive proposition. We hypothesized that the delay of activation onset from the device-detected, far-field electrogram (EGM) to the near-field, bipole EGM would allow the differentiation of ventricular tachycardias (VTs) from SVTs. Proof of principle was demonstrated by rapid pacing in the right atrium, right ventricle, and left ventricle in healthy patients undergoing atrial fibrillation ablation procedures (n = 17). Using real-life ICD recordings, the equivalent measurements were made in a derivation cohort (n = 26) and cutoff predictive values obtained. Finally, the selected values were validated in a separate group of recordings (n = 82). In healthy patients, significant differences in the far-field to near-field EGM activation onsets were observed between right atrial (14.7 ± 2.7 ms), right ventricular (36.3 ± 8 ms), and left ventricular (57.8 ± 10.3 ms; P < .001) pacing. In the derivation ICD cohort, the median far-field to near-field onset delay wassignificantly shorter in SVT (24.5 ms; interquartile range, 15.3-47.5 ms) than in VT (118.5 ms; interquartile range, 102.5-131.5 ms) (P < .001). Using a cutoff of 100 ms in the validation cohort, SVT was successfully discriminated from VT with a sensitivity and specificity of 88% and a negative predictive value of 94.2%. The delay between far-field and near-field EGMs offers a potential new discrimination tool to reduce inappropriate ICD therapies and aid interpretation of single-lead device tracings.

651Six year follow-up of the initial dutch subcutaneous implantable cardioverter-defibrillator cohort: Long term complications and battery longevity

651Six year follow-up of the initial dutch subcutaneous implantable cardioverter-defibrillator cohort: Long term complications and battery longevity

Single-coil and dual-coil defibrillator leads and association with clinical outcomes in a complete Danish nationwide ICD cohort

The best choice of defibrillator lead in patients with routine implantable cardioverter-defibrillator (ICD) is not settled. Traditionally, most physicians prefer dual-coil leads but the use of single-coil leads is increasing. The purpose of this study was to compare clinical outcomes in patients with single- and dual-coil leads. All 4769 Danish patients 18 years or older with first-time ICD implants from 2007 to 2011 were included from the Danish Pacemaker and ICD Register. Defibrillator leads were 38.9% single-coil leads and 61.1% dual-coil leads. The primary end point was all-cause mortality. Secondary end points were lowest successful energy at implant defibrillation testing, first shock failure in spontaneous arrhythmias, structural lead failure, and lead extraction outcomes. Single-coil leads were associated with lower all-cause mortality with an adjusted hazard ratio of 0.85 (95% confidence interval 0.73-0.99; P = .04). This finding was robust in a supplementary propensity score-matched analysis. However, dual-coil leads were used in patients with slightly higher preimplant morbidity, making residual confounding by indication the most likely explanation for the observed association between lead type and mortality. The lowest successful defibrillation energy was higher using single-coil leads (23.2 ± 4.3 J vs 22.1 ± 3.9 J; P < .001). No significant differences were observed for other secondary end points showing high shock efficacies and low rates of lead failures and extraction complications. Shock efficacy is high for modern ICD systems. The choice between single-coil and dual-coil defibrillator leads is unlikely to have a clinically significant impact on patient outcomes in routine ICD implants.

Left ventricular sphericity independently predicts appropriate implantable cardioverter-defibrillator therapy

Whether echocardiographic markers of remodeling are associated with ventricular tachyarrhythmias is unknown. The purpose of this study was to determine whether a transthoracic echocardiographic (TTE) marker of spherical left ventricular (LV) remodeling is associated with appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with primary prevention ICDs. From TTE images, we calculated sphericity index (SI), the ratio of biplane LV end-diastolic volume to the volume of a hypothetical sphere with a diameter of the LV end-diastolic length, and examined the relation between SI and therapy for ventricular tachyarrhythmias in 278 patients with primary prevention ICDs and in 50 controls without structural heart disease or ventricular arrhythmias. SI in normal healthy adult subjects and in subjects receiving ICDs was 0.44 ± 0.02 and 0.65 ± 0.04, respectively (P <.001). Median time to first appropriate ICD therapy was significantly shorter in ICD patients with SI in the upper vs lower 50% of SI values (1.40 vs 2.38 years, P = .02 for conventional ICD patients; 1.54 vs 2.65 years, P = .02 for cardiac resynchronization therapy-defibrillator [CRT-D] patients). In multivariable Cox regression analysis, SI in the upper 50% was independently associated with appropriate ICD therapy after multivariable adjustment (hazard ratio 2.2, P = .03 for ICD cohort; hazard ratio 4.4, P = .01 for CRT-D cohort). SI was not associated with total mortality in either cohort. SI is associated with appropriate ICD therapy, but not total mortality, in patients receiving primary prevention ICDs. These observations suggest spherical LV remodeling may predispose to ventricular arrhythmias. Furthermore, SI appears to add predictive accuracy for appropriate ICD therapy in patients with reduced ejection fraction.

Impact of Implantable Cardioverter Defibrillators on Survival of Patients with Centrifugal Left Ventricular Assist Devices.

Both implantable cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) have a positive impact on survival in the heart failure population. We sought to determine whether these positive effects on survival are additive or whether LVAD therapy supersedes ICD therapy. We analyzed survival data of patients implanted with nonpulsatile LVADs between October 2004 and March 2013. Survival in patients with ICDs (n = 64) was compared to those without ICDs (n = 36). Patients exited the study at the time of heart transplantation or death. A total of 100 patients underwent LVAD implantation during this time. Patients had a mean follow-up time of 364 ± 295 days. Death occurred in 15 (38%) patients in the no ICD group versus 18 (30%) in the ICD group. Univariate analysis demonstrated a marginal early survival benefit at up to 1 year post-LVAD implant in the ICD cohort; however, at time points greater than 1 year there was no statistically significant benefit in ICD therapy in LVAD patients (P = 0.56). Multivariate analysis did not show any significant predictor of survival. There were no patients who died of sudden cardiac death. There was no significant difference in the time to heart transplantation (443 days ± 251 no ICD vs 372 days ± 277 ICD, P = 0.37). The benefit of ICD therapy in the setting of continuous flow LVAD therapy is uncertain. Although prolonged ventricular arrhythmias (VAs) may potentially impact on patient survival, LVAD therapy is beneficial in prevention of sudden cardiac death due to VAs.

Implantable cardioverter-defibrillators and subsequent cancer risk: a nationwide population-based cohort study.

Despite increasing use of implantable cardioverter-defibrillators (ICDs) and reports linking selected bio-implants with cancer, the cancer risk associated with implanted ICDs remains unknown. The objective of our study was to examine cancer risk among ICD recipients. We conducted a population-based cohort study using medical registries covering the entire Danish population. We identified all first-time ICD recipients during the period of 2000-11 and determined their subsequent cancer incidence. Standardized incidence ratios (SIRs) were computed by comparing observed cancer incidence in the ICD cohort with expected cancer incidence based on national incidence rates according to age, sex, and year of diagnosis. A total of 6723 ICD recipients were followed for up to 12 years (median 2.8 years) and contributed a total of 23 254 person-years of follow-up. Compared with the general population, ICD recipients had a slightly elevated overall risk of cancer [SIR = 1.1 (95% confidence interval (CI): 1.0-1.2)]. This was driven by the cancer risk among patients with ischaemic heart disease (IHD) [SIR = 1.1 (95% CI: 1.0-1.3)], which, as expected, was particularly elevated for tobacco-related cancers [SIR = 1.4 (95% CI: 1.2-1.6)]. Importantly, ICD recipients without IHD were not at increased cancer risk [SIR = 1.0 (95% CI: 0.8-1.3)]. This nationwide population-based cohort study with up to 12-year follow-up did not indicate a causal relation between ICD implantation and cancer. However, more follow-up data are needed to entirely rule out risks for individual cancer types.

Primary prevention implantable cardioverter defibrillators in end-stage kidney disease patients on dialysis: a matched cohort study

Sudden cardiac death is the leading cause of death among end-stage kidney disease patients (ESKD) on dialysis, but the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in this population is uncertain. We conducted this investigation to compare the mortality of dialysis patients receiving a primary prevention ICD with matched controls. We used data from the National Cardiovascular Data Registry's ICD Registry to select dialysis patients who received a primary prevention ICD, and the Get with the Guidelines-Heart Failure Registry to select a comparator cohort. We matched ICD recipients and no-ICD patients using propensity score techniques to reduce confounding, and overall survival was compared between groups. We identified 108 dialysis patients receiving primary prevention ICDs and 195 comparable dialysis patients without ICDs. One year (3-year) mortality was 42.2% (68.8%) in the ICD registry cohort compared with 38.1% (75.7%) in the control cohort. There was no significant survival advantage associated with ICD [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.66-1.13, log-rank P = 0.29]. After propensity matching, our analysis included 86 ICD patients and 86 matched controls. Comparing the propensity-matched cohorts, 1 year (3 years) mortality was 43.4% (74.0%) in the ICD cohort and 39.7% (76.6%) in the control cohort; there was no significant difference in mortality outcome between groups (HR = 0.94, 95% CI: 0.67-1.31, log-rank P = 0.71). We did not observe a significant association between primary prevention ICDs and reduced mortality among ESKD patients receiving dialysis. Consideration of the potential risks and benefits of ICD implantation in these patients should be undertaken while awaiting the results of definitive clinical trials.

Psychological Indices as Predictors for Phantom Shocks in Implantable Cardioverter Defibrillator Recipients

A phantom shock-the sensation of an implantable cardioverter defibrillator (ICD) discharge in the absence of an actual discharge-is a phenomenon that can occur in ICD patients. Little is known about the influence of psychological factors on the incidence of phantom shocks. We evaluated psychological correlates of phantom shocks 2 years post-ICD implant in a cohort of Dutch ICD recipients. Consecutive patients (N = 300; 87.5% men; mean age = 62.3) willing to participate in a prospective study (Twente ICD Cohort Study) on psychological factors in ICD recipients received an ICD between September 2007 and February 2010. At baseline, patients complete the 36-item Short Form Health Survey, Hospital Anxiety and Depression Scale, and the Type D Scale. Lifetime presence of anxiety and depression was assessed with the MINI structural interview. During a follow-up of 24 months, 16 patients (5.4%) experienced a phantom shock. Median time to (first) phantom shock was 13 weeks (range 0-48 weeks). In univariable analysis, no significant relationships were found between clinical or psychological indices and the occurrence of phantom shocks, nor was there an association between phantom shocks and type D personality, symptoms of anxiety, or a history of anxiety and depression. Neither symptoms of anxiety and depression nor psychiatric history were associated with the occurrence of phantom shocks. Further studies using more explorative, qualitative research techniques are warranted to examine the correlates of phantom shocks.

Predictors of Pacemaker Dependence and Pacemaker Dependence as a Predictor of Mortality in Patients with Implantable Cardioverter Defibrillator

The prevalence, predictors, and survival for the development of pacemaker dependence (PD) in patients implanted with an implantable cardioverter defibrillator (ICD) are unknown. This was a retrospective analysis of 1,550 consecutive patients with ICD implantation at a single center from 1996 to 2008 with a mean of 4.2 ± 3.4 years. Patients with implant intrinsic heart rates less than 40 beats/min (n = 48) and cardiac resynchronization therapy (n = 444) were excluded leaving 1,058 patients in this study. PD was defined as an intrinsic rhythm <40 beats/min after inhibiting the pacemaker, <50 beats/min with transient symptoms of dizziness relieved by resumption of pacing and right ventricle pacing despite algorithms to promote intrinsic conduction at the 3 monthly follow-up ICD clinic visits. Multivariate regression and Cox proportional hazard models were used for analysis. The mean age was 64 ± 13 years; 79% were male with a primary indication for the ICD in 57%. PD occurred in 142 (13.4%) of patients, with a mean time to PD of 2.6 ± 1.9 years. PD was associated with a 48% increased odds for mortality versus non-PD ICD patients during the mean follow-up time of 4.2 ± 3.4 years (adjusted odds ratio = 1.48 [95% confidence interval 1.080-2.042]; P = 0.015). Older age, a history of atrial fibrillation, amiodarone use, and secondary prevention were the strongest predictors for the development of PD. In this single-center ICD cohort, the development of PD was not uncommon and was associated with decreased survival.

Application of the Multicenter Automatic Defibrillator Implantation Trial II Risk Score in a Nontrial Setting

A post hoc analysis of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II showed that patients with high mortality risk score did not benefit from implantable cardioverter-defibrillator (ICD) therapy. We sought to determine whether MADIT II risk score can identify patients with greater mortality in a nontrial "real-world" setting. We included 382 consecutive patients who received ICD for primary prevention of sudden cardiac death at the Minneapolis Veterans Affairs Medical Center from 2006 to 2010. MADIT II score was calculated by assigning 1 point each for age >70 years, New York Heart Association class >II, atrial fibrillation, QRS >0.12 seconds, and blood urea nitrogen level >26 mg/dl. Scores 0, 1 to 2, and ≥3 were classified as low, intermediate, and high risk, respectively. Of the 382 patients, 14% were low risk, 54% intermediate risk, and 32% high risk. After 3.0 ± 1.6 years of follow-up, incidence of appropriate ICD shocks was similar (p = 0.21) across MADIT II risk score categories. However, mortality rate was 21, 54, and 134 per 1,000 patient-year follow-up in low, intermediate, and high-risk patients, respectively, p <0.0001. Compared with low-risk patients, mortality was 6.4× greater in high-risk patients (hazard ratio 6.36, 95% confidence interval 1.9 to 20.5; p = 0.002). The c-index for the MADIT II score for predicting death was 0.69 (95% confidence interval 0.63 to 0.75). In conclusion, MADIT II risk score successfully identified patients with greater mortality in a nontrial-based, primary-prevention ICD cohort.

Gender studies in cardiovascular medicine: Getting to the heart of the matter

Since the first implantable cardioverter-defibrillator (ICD) implants for the prevention of sudden cardiac death (SCD), we have asked how to best risk stratify patients. Cardiac resynchronization therapy (CRT) has offered further options for the treatment of patients with congestive heart failure, but also has raised questions regarding the mechanism of response to therapy. Many clinical trials have evaluated the efficacy of ICD and CRT devices, providing clear evidence that they reduce the risk of SCD and improve congestive heart failure. Data from these trials, however, suggest that efficacy may differ between men and women. We have also learned that women are underrepresented in these trials and device therapy is clinically underused in women. In this issue of HeartRhythm, Loring et al test the hypothesis that myocardial scarring is less in women than in men, influencing device benefit. This article highlights both the issues of gender-related device benefit and the challenge of gender imbalance in clinical trials. The authors evaluated myocardial scarring by using contrast enhanced magnetic resonance imaging (MRI) in patients undergoing ICD or CRT-D implantation. MRI scar characterization is emerging as a prognostic variable in patients with cardiomyopathy. Thus, it is both timely and appropriate to evaluate gender differences of myocardial scar in patients undergoing ICD or CRT-D implantation. Previously, the Framingham study showed that the incidence of SCD in women is o50% that of men. This sets the stage for the present study evaluating gender-related scar patterns. In this study, the ICD cohort consisted of 56 women and 179 men. Overall, women had smaller scar sizes compared to men, likely owing to a higher prevalence of nonischemic cardiomyopathy (NICM). The pattern of delayed enhancement on MRI in NICM is distinct, identifying irreversible myocardial injury, the extent of which has been considered a marker of arrhythmia risk that can lead to appropriate device therapy. In patients with an ICD or CRT-D, a larger scar identified by contrast MRI may explain, at least in part, the higher probability of appropriate device

Cardiac MRI scar patterns differ by sex in an implantable cardioverter-defibrillator and cardiac resynchronization therapy cohort.

Recent meta-analyses suggest that the effectiveness of cardiac devices may differ between genders. Compared to men, women may not benefit as much from implantable cardioverter-defibrillators (ICDs), yet benefit more from cardiac resynchronization therapy (CRT). Myocardial scar burden is associated with increased incidence of appropriate ICD shocks but decreased response to CRT and may explain gender differences in device benefit. To test the hypothesis that the extent of myocardial scar is less in women than men. In 235 patients referred for primary prevention ICDs who underwent cardiac magnetic resonance imaging, we compared scar size by gender. Analyses were performed for all patients (ICD cohort) and those receiving biventricular pacemakers (CRT subgroup). In the ICD cohort, women (vs men) had a higher prevalence of nonischemic cardiomyopathy (NICM; 64% vs 39%; P<.001), which accounted for a smaller overall scar burden (0.5% vs 13%, P<.01). Likewise, in the CRT subgroup, the higher prevalence of NICM in women (83% vs 46%; P = .01) also contributed to a smaller scar size (0% vs 13%; P<.01). Women also had significantly less scarring of the inferolateral left ventricular wall. In a cohort of patients undergoing clinically indicated ICD and CRT, women had less myocardial scar than did men. This difference was primarily driven by a higher prevalence of NICM in women. These findings may have important implications for the future study of gender disparities in ICD and CRT outcomes.

Plasma Biomarkers for Prediction of Sudden Cardiac Death

Sudden cardiac death (SCD) accounts for most cardiovascular deaths in the United States, claiming an estimated 300 000 lives per year.1 Despite intense efforts to develop resuscitation techniques, survival rates are still low, at ≈5%.2 This has led to a renewed focus in this field directed toward optimizing risk prediction to identify the candidate that would qualify for prophylactic or preventive interventions.3 At present, the clinical risk stratification is largely limited to the use of left ventricular ejection fraction (LVEF) for identifying primary prophylaxis candidates, but specificity of this predictor is modest.4 Moreover, the absolute numbers of these high-risk patients in the general population are low. Instead, the highest prevalence of SCD is likely observed among previously asymptomatic individuals, even though it is well-known that coronary artery disease (CAD) is present in most SCD cases.5 This underscores the need for the development of risk stratification models that can be applied to the general population where the largest health benefit is likely to be realized. The underpinnings of SCD are complex, and it is reasonable to believe that the risk stratification instrument of the future is likely to involve other components beyond clinical risk markers. Novel genomic variants show promise but are still in early phases of development as risk stratification targets. However, the “unbiased” approaches made possible through genomewide association studies have led to the recent identification of specific genetic variants that could predict SCD.6,7 This has reignited the interest in plasma biomarkers as a means for risk stratification. This article will review the emerging evidence and role of plasma biomarkers in predicting SCD in the general population and suggest a blueprint for future studies of potential utility. ### Uniform Definition of SCD Given the complexity and dynamic nature of the condition, there has been some variability …

Implantable Defibrillators for the Prevention of Mortality in Patients With Nonischemic Cardiomyopathy

Implantable cardioverter defibrillator (ICD) therapy is effective in primary and secondary prevention of sudden cardiac death among patients with prior myocardial infarction and depressed ejection fraction. However, conclusive evidence of survival benefit in patients with nonischemic cardiomyopathy (NICM) is still lacking. To determine whether ICD therapy reduces all-cause mortality in patients with NICM. MEDLINE (1966-2004), EMBASE (1991-2004), the Cochrane Central Register of Controlled Trials (through first quarter, 2004), reports presented at scientific meetings (2003-2004), and bibliographic review of secondary sources. Search terms included defibrillator, randomized controlled trials, clinical trials, and sudden death. Eligible studies were prospective randomized controlled trials of ICD or combined cardiac resynchronization therapy and defibrillator (CRT-D) vs medical therapy enrolling at least some individuals with NICM and reporting all-cause mortality as an outcome. Of 675 potentially relevant articles screened initially, 8 reports of randomized trials enrolling a total of 2146 patients with NICM were included. Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, primary end point, mortality of ICD cohort, and mortality of control cohort. Five primary prevention trials enrolling 1854 patients with NICM were identified; pooled analysis suggested a significant reduction in total mortality among patients randomized to ICD or CRT-D vs medical therapy (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.55-0.87; P = .002). Mortality reduction remained significant even after elimination of CRT-D trials. Two of the 3 secondary prevention trials presented subgroup estimates for ICD efficacy in NICM. Pooled analysis of these secondary prevention trials (n = 256 patients with NICM) indicated an equivalent but nonsignificant mortality reduction with ICD therapy (RR, 0.69; 95% CI, 0.39-1.24; P = .22). Analysis of all 7 trials combined demonstrated a statistically significant 31% overall reduction in mortality with ICD therapy (RR, 0.69; 95% CI, 0.56-0.86; P = .002). ICD therapy appears to significantly reduce mortality in selected patients with NICM.