Dyssynchrony and Response to Cardiac Resynchronization Therapy in Heart Failure Patients With Unfavorable Electrical Characteristics.

BACKGROUND: Among heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT), those with unfavorable electrical characteristics (UEC) are less frequently CRT responders. OBJECTIVES: In this study, the authors sought to evaluate the relationship between preprocedural echocardiographic parameters of electromechanical dyssynchrony (EMD) and outcome following CRT. METHODS: Among 551 patients receiving CRT, 121 with UEC, defined as atypical left bundle branch, presence of right bundle branch block, or unspecified intraventricular conduction disturbance, were enrolled. Indices of EMD were presence of septal flash, apical rocking, septal deformation patterns, and global wasted work (GWW), determined with the use of speckle-tracking strain echocardiography. Endpoints were response to CRT, defined as a relative decrease in left ventricular end-systolic volume ≥15% at 9-month postoperative follow-up, and all-cause death or HF hospitalization during follow-up. RESULTS: Among the 121 patients, 68 (56%) were CRT responders. In multivariate analysis, GWW ≥200 mm Hg% (adjusted odds ratio [aOR]: 4.17 [95% CI: 1.33-14.56]; P = 0.0182) and longitudinal strain septal contraction patterns 1 and 2 (aOR: 10.05 [95% CI: 2.82-43.97]; P < 0.001) were associated with CRT response. During a 46-month follow-up (IQR: 42-55 months), survival free from death or HF hospitalization increased with the number of positive criteria (87% for 2, 59% for 1, and 27% for 0). After adjustment for established predictors of outcome in patients receiving CRT, absence of either of the 2 criteria remained associated with a considerable increased risk of death and/or HF hospitalization (adjusted HR: 4.83 [95% CI: 1.84-12.68]; P = 0.001). CONCLUSIONS: In patients with UEC, echocardiographic assessment of EMD may help to select patients who will derive benefit from CRT. (Echocardiography in Cardiac Resynchronization Therapy [Echo-CRT]; NCT02986633).

Caseous necrosis of the mitral annulus: a new feature of drug-induced valvular heart disease? Case series.

BACKGROUND: Drug-induced valvular heart disease (DI-VHD) is a well-defined condition associated with specific pathology features. However, clinical presentations may broadly vary and thereby make DI-VHD diagnosis more challenging. CASE SUMMARY: We report two patients with a history of benfluorex administration, who developed extensive mitral calcific lesions which evolved towards caseous necrosis. DISCUSSION: Prospective follow-up over several years of these two patients who initially had typical DI-VHD findings provided monitoring evidence of extensive calcifications and subsequent caseous necrosis. These reports suggest a link between calcific heart injury and benfluorex exposure. The diagnosis of DI-VHD may be overlooked at this late stage.

Clinical Significance of Global Wasted Work in Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: The relationship between myocardial work assessment using pressure-strain loops by echocardiography before cardiac resynchronization therapy (CRT) and response to CRT has been recently revealed. Among myocardial work parameters, the impact of left ventricular myocardial global wasted work (GWW) on response to CRT and outcome following CRT has been seldom studied. Hence, the authors evaluated the relationship between preprocedural GWW and outcome in a large prospective cohort of patients with heart failure (HF) and reduced ejection fraction receiving CRT. METHODS: The study included 249 patients with HF. Myocardial work indices including GWW were calculated using speckle-tracking strain two-dimensional echocardiography using pressure-strain loops. End points of the study were (1) response to CRT, defined as left ventricular reverse remodeling and/or absence of hospitalization for HF, and (2) all-cause death during follow-up. RESULTS: Median follow-up duration was 48 months (interquartile range, 43-54 months). Median preoperative GWW was 281 mm Hg% (interquartile range, 184-388 mm Hg%). Preoperative GWW was associated with CRT response (area under the curve, 0.74; P < .0001), and a 200 mm Hg% threshold discriminated CRT nonresponders from responders with 85% specificity and 50% sensitivity, even after adjustment for known predictors of CRT response (adjusted odds ratio, 4.03; 95% CI, 1.91-8.68; P < .001). After adjustment for established predictors of outcome in patients with HF with reduced ejection fraction receiving CRT, GWW < 200 mm Hg% remained associated with a relative increased risk for all-cause death compared with GWW ≥ 200 mm Hg% (adjusted hazard ratio, 2.0; 95% CI, 1.1-3.9; P = .0245). Adding GWW to a baseline model including known predictors of outcome in CRT resulted in an improvement of this model (χ2 to improve 4.85, P = .028). The relationship between GWW and CRT response and outcome was stronger in terms of size effect and statistical significance than for other myocardial work indices. CONCLUSIONS: Low preoperative GWW (<200 mm Hg%) is associated with absence of CRT response in CRT candidates and with a relative increased risk for all-cause death. GWW appears to be a promising parameter to improve selection for CRT of patients with HF with reduced ejection fraction.

Clinical and prognostic implications of phenomapping in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Despite having an indication for cardiac resynchronization therapy according to current guidelines, patients with heart failure with reduced ejection fraction who receive cardiac resynchronization therapy do not consistently derive benefit from it. AIM: To determine whether unsupervised clustering analysis (phenomapping) can identify distinct phenogroups of patients with differential outcomes among cardiac resynchronization therapy recipients from routine clinical practice. METHODS: We used unsupervised hierarchical cluster analysis of phenotypic data after data reduction (55 clinical, biological and echocardiographic variables) to define new phenogroups among 328 patients with heart failure with reduced ejection fraction from routine clinical practice enrolled before cardiac resynchronization therapy. Clinical outcomes and cardiac resynchronization therapy response rate were studied according to phenogroups. RESULTS: Although all patients met the recommended criteria for cardiac resynchronization therapy implantation, phenomapping analysis classified study participants into four phenogroups that differed distinctively in clinical, biological, electrocardiographic and echocardiographic characteristics and outcomes. Patients from phenogroups 1 and 2 had the most improved outcome in terms of mortality, associated with cardiac resynchronization therapy response rates of 81% and 78%, respectively. In contrast, patients from phenogroups 3 and 4 had cardiac resynchronization therapy response rates of 39% and 59%, respectively, and the worst outcome, with a considerably increased risk of mortality compared with patients from phenogroup 1 (hazard ratio 3.23, 95% confidence interval 1.9-5.5 and hazard ratio 2.49, 95% confidence interval 1.38-4.50, respectively). CONCLUSIONS: Among patients with heart failure with reduced ejection fraction with an indication for cardiac resynchronization therapy from routine clinical practice, phenomapping identifies subgroups of patients with differential clinical, biological and echocardiographic features strongly linked to divergent outcomes and responses to cardiac resynchronization therapy. This approach may help to identify patients who will derive most benefit from cardiac resynchronization therapy in "individualized" clinical practice.

Prognostic Impact of the Ratio of Acceleration Time to Ejection Time in Patients With Low Gradient Severe Aortic Stenosis and Preserved Ejection Fraction.

The clinical management of patients with low gradient severe aortic stenosis (LG-SAS) and preserved left ventricular ejection fraction (LVEF) remains challenging owing to their heterogeneity. The aim to this study was to evaluate the relation between an ejection dynamic parameter linked to AS severity and outcome, the ratio of acceleration time (AT) to ejection time (ET), in a cohort of patients with LG-SAS and preserved LVEF. Three hundred and fifty-six patients with LG-AS (defined by AVA ≤1 cm² and/or AVAi ≤0.6 cm²/m² and mean aortic pressure gradient <40 mm Hg) and preserved LVEF ≥50% were studied. The relation between AT/ET and all-cause and cardiac mortality during follow-up was studied. Median follow-up was 41 months (interquartile range, 35 to 47 months). Median AT/ET was 0.32 (interquartile range, 0.29 to 0.36). The 5-year estimates of all-cause and cardiac mortality were respectively 57 ± 7%, 36 ± 7% for patients with AT/ET >0.36 versus 43 ± 4%, 16 ± 3% for patients with AT/ET ≤0.36 (p = 0.024 and p <0.001, respectively). After adjustment on known predictors of outcome including aortic valve replacement used as a time-dependent covariate, there was a significant increase in all-cause mortality risk for patients with AT/ET >0.36 (adjusted hazard ratio 2.04 [95% confidence interval, 1.32 to 3.13]; p = 0.001) and cardiac mortality risk (adjusted hazard ratio 2.89 [95% confidence interval, 1.54 to 5.43]; p<0.001) compared with patients with AT/ET ≤0.36. The association of AT/ET >0.36 and all-cause or cardiac mortality risk was consistent in subgroups of patients with LG-SAS and preserved EF. In conclusion, an AT/ET ratio of more than 0.36 is an independent predictor of mortality in patients with LG-SAS and preserved EF.