Sex Differences in Left Ventricular Electrical Dyssynchrony and Outcomes with Cardiac Resynchronization Therapy

BACKGROUND: Women seem to derive more benefit from cardiac resynchronization therapy (CRT) than men, even after accounting for the higher burden of risk factors for nonresponse often observed in men. OBJECTIVE: To assess for sex-specific differences in left ventricular (LV) electrical dyssynchrony as a contributing electrophysiological explanation for the greater degree of CRT benefit among women. METHODS: We compared the extent of baseline LV electrical dyssynchrony, as measured by the QRS area (QRSA), among men and women with left bundle branch block (LBBB) undergoing CRT at Duke University (n = 492, 35% women) overall and in relation to baseline QRS characteristics using independent sample t tests and Pearson correlation coefficients. Cox regression analyses were used to relate sex, QRSA, and QRS characteristics to the risk of cardiac transplantation, LV assist device implant, or death. RESULTS: Although the mean QRS duration (QRSd) did not differ by sex, QRSA was greater for women vs men (113.8 μVs vs 98.2 μVs, P < .001), owing to differences in the QRSd <150 ms subgroup (92.3 ± 28.7 μVs vs 67.6 ± 26.2 μVs, P < .001). Among those with nonstrict LBBB, mean QRSd was similar but QRSA was significantly greater among women than men (96.0 ± 25.0 μVs vs 63.6 ± 26.2 μVs, P < .001). QRSA was similar among men and women with strict LBBB (P = .533). Female sex was associated with better long-term outcomes in an unadjusted model (hazard ratio 0.623, confidence interval 0.454–0.857, P = .004) but sex no longer predicted outcomes after accounting for differences in QRSA. CONCLUSIONS: Our study suggests that sex-specific differences in LV dyssynchrony contribute to greater CRT benefit among women. Standard QRSd and morphology assessments seem to underestimate the extent of LV electrical dyssynchrony among women with LBBB

The Association of a classical left bundle Branch Block Contraction Pattern by vendor-independent strain echocardiography and outcome after cardiac resynchronization therapy

Background: The association of a Classical left bundle branch block (LBBB) contraction pattern and better outcome after cardiac resynchronization therapy (CRT) has only been studied using vendor-specific software for echocardiographic speckle-tracked longitudinal strain analysis. The purpose of this study was to assess whether a Classical LBBB contraction pattern on longitudinal strain analysis using vendor-independent software is associated with clinical outcome in CRT recipients with LBBB. Methods: This was a retrospective cohort study including CRT recipients with LBBB, heart failure, and left ventricular (LV) ejection fraction ≤35%. Speckle-tracked echocardiographic longitudinal strain analysis was performed retrospectively on echocardiograms using vendor-independent software. The presence of a Classical LBBB contraction pattern was determined by consensus of two readers. The primary end point was a composite of time to death, heart transplantation or LV assist device implantation. Secondary outcome was ≥15% reduction in LV end-systolic volume. Intra- and inter-reader agreement of the longitudinal strain contraction pattern was assessed by calculating Cohen's κ. Results: Of 283 included patients, 113 (40%) were women, mean age was 66 ± 11 years, and 136 (48%) had ischemic heart disease. A Classical LBBB contraction pattern was present in 196 (69%). The unadjusted hazard ratio for reaching the primary end point was 1.93 (95% confidence interval, 1.36-2.76, p &lt; 0.001) when comparing patients without to patients with a Classical LBBB contraction pattern. Adjusted for ischemic heart disease and QRS duration &lt; 150 milliseconds the hazard ratio was 1.65 (95% confidence interval, 1.12-2.43, p = 0.01). Of the 123 (43%) patients with a follow-up echocardiogram, 64 of 85 (75%) of patients with a Classical LBBB contraction pattern compared to 13 of 38 (34%) without, had ≥15% reduction in LV end-systolic volume (p &lt; 0.001). Cohen's κ were 0.86 (95% confidence interval, 0.71-1.00) and 0.42 (95% confidence interval, 0.30-0.54) for intra- and inter-reader agreement, respectively. Conclusion: Using vendor-independent strain software, a Classical LBBB contraction pattern is associated with better outcome in CRT recipients with LBBB, but inter-reader agreement for the classification of contraction pattern is only moderate.</p

Association Between ECG Abnormalities and Fatal Cardiovascular Disease Among Patients With and Without Severe Mental Illness

BACKGROUND: ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. METHODS AND RESULTS: We cross-linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10-year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (P<0.001). Severe mental illness was associated with fatal CVD across no (HR, 2.17; 95% CI, 1.95–2.43), minor (HR, 1.90; 95% CI, 1.49–2.42), and major (HR, 1.40; 95% CI, 1.26–1.55) ECG abnormalities compared with controls. Across age-and sex-specific subgroups, SMI patients with ECG abnormalities but no CVD at baseline had highest standardized 10-year absolute risks of fatal CVD. CONCLUSIONS: ECG abnormalities conferred a poorer prognosis among patients with SMI compared with controls without mental illness. SMI patients with ECG abnormalities but no CVD represent a high-risk population that may benefit from greater surveillance and risk management

Special issue of the Journal of Electrocardiology to commemorate Dr. Galen Wagner (1939–2016)

Cardiolog