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

BACKGROUND: 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. OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Relationship between device-detected burden and duration of atrial fibrillation and risk of ischemic stroke.

BACKGROUND: Wider availability of continuous rhythm monitoring has made feasible the incorporation of metrics of atrial fibrillation (AF) burden and duration into the decision to initiate anticoagulation. However, the relationship between thresholds of burden and duration and underlying risk factors at which anticoagulation should be considered remains unclear. OBJECTIVE: The purpose of this study was to evaluate the relationships of these metrics with each other and the outcome of stroke/transient ischemic attack (TIA). METHODS: We identified patients with cardiovascular implantable electronic devices (CIEDs) with atrial leads who had at least 1 interrogation in 2016 demonstrating nonpermanent AF and were not receiving oral anticoagulation (OAC). We evaluated the relationship between burden (ie, percentage of time spent in AF), the longest single episode of AF, and risk factors (ie, CHA2DS2-VASc score) in predicting risk of stroke/TIA. RESULTS: The study included 384 patients with mean follow-up of 3.2 ± 0.8 years and incidence of stroke/TIA of 14.8% during follow-up (∼4.6% per year). The burden of AF and the duration of longest episode demonstrated a significant positive correlation to each other but not CHA2DS2-VASc score. Importantly, although the CHA2DS2-VASc score was predictive of stroke/TIA, neither burden nor duration was associated with stroke/TIA. CONCLUSION: Among patients with CIED-detected AF not receiving OAC, the amount of AF (measured by either burden or duration) does not seem to significantly impact stroke risk, whereas CHA2DS2-VASc score does. These data suggest that among patients with CIED-detected AF, once AF occurs, stroke risk seems to be predominantly driven by underlying risk factors.

Significance of leukocytosis prior to cardiac device implantation.

INTRODUCTION: Infection remains a dreaded complication after cardiac implanted electronic device (CIED) placement. The prognostic value of the preoperative white blood cell (WBC) count, in the absence of other signs of infection, at time of CIED placement as a predictor of postoperative infection, has not been previously examined. METHODS: The study population included 1,247 consecutive device implantations over a 4-year period that met inclusion criteria. The association between preoperative WBC count and resultant infection postoperatively was examined. Early infection was defined as definite infection of the pocket or lead system or development of systemic infection identified <60 days after implantation. Preoperative WBC counts were obtained within 48 hours of the procedure. RESULTS: Baseline characteristics of the population studied were mean age of 65 years, 66% men, and 72% Caucasian. Pacemakers, implantable cardioverter defibrillators (ICDs), and biventricular ICDs were implanted in 41%, 44%, and 15%, respectively. Average procedure time was 174 minutes ± 80. Of 1,247 device implantations, there were 10 infections (0.8%). Mean preprocedure WBC count in those diagnosed with infection was 8.1 × 103 /uL (range 5-11.7) and in those without infection was 7.8 × 10(3)/uL (range 2.3-29) (P = 0.73). Cases resulting in infection demonstrated minimal change in WBC count (mean +5.5 ± 26.5%). There was no statistically significant difference in preprocedure WBC count between the two groups (P = 0.7). Regardless of preprocedural WBC, no patients had other signs and symptoms of infection at time of device implantation. CONCLUSION: As an isolated finding, an elevated preprocedure WBC should not delay the implantation of an indicated device.

Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT.

INTRODUCTION: Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes. METHODS: The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible. RESULTS: One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001). CONCLUSIONS: Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

Sex Differences in Device Therapies for Ventricular Arrhythmias or Death in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) Trial.

INTRODUCTION: Studies suggest that women with ischemic heart disease are less likely to experience appropriate ICD therapies for ventricular arrhythmias (VT/VF). We evaluated the influence of sex on arrhythmic events or death in subjects enrolled in MADIT-CRT. METHODS AND RESULTS: Arrhythmic event rates, defined as VT/VF treated with defibrillator therapy or all-cause death, were determined among 1,790 subjects enrolled in MADIT-CRT with documented 3-year follow-up. Predictors of VT/VF/death were identified using multivariate analysis. Ninety-one (21%) women and 466 (35%) men experienced VT/VF/death over the follow-up period. The overall probability of VT/VF/death was significantly lower in women versus men (HR 0.62; P < 0.001). The probability of VT/VF/death was the lowest in women with ischemic heart disease (HR 0.51; P = 0.003). In ICD subjects, the 3-year risk of VT/VF was lower in ischemic women versus men (P = 0.021), and in nonischemic women versus men (P = 0.049). The probability of VT/VF/death was significantly lower in women (HR 0.52; P = 0.007) and men (HR 0.74; P = 0.018) with LBBB who received CRT-D. Appropriate shock therapy strongly correlated with increased risk of death during postshock follow-up in women (HR 5.18; P = 0.001) and men (HR 1.63; P = 0.033); interaction P value of 0.034. CONCLUSION: In this substudy of MADIT-CRT, sex, etiology of heart disease and type of device implanted significantly influenced subsequent risk for VT/VF or death. Women with ischemic heart disease and women with LBBB who received CRT-D had the lowest incidence of VT/VF or death when compared to men. Appropriate shock therapy was a strong predictor of death, particularly in women.

Should a Patient with Severe Left Ventricular Dysfunction, Congestive Heart Failure, and Right Bundle Branch Block QRS Receive Cardiac Resynchronization Therapy?

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure and mechanical dyssynchrony. Patients with left bundle branch block and QRS greater than or equal to 150 milliseconds derive the greatest clinical response. Patients with right bundle branch block (RBBB) may not derive the same benefit. The reasons for this disparity are unclear, but may relate to differences in biventricular activation sequence and timing in the presence of left versus RBBB. This article provides a comprehensive review of current understanding of the clinical effectiveness of CRT in patients with left ventricular dysfunction and RBBB.