Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study.

BACKGROUND: The effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. OBJECTIVES: The study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. METHODS: Sixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. RESULTS: Patients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography-derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro-brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. CONCLUSION: LBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

BACKGROUND: The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. METHODS: We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi) > .7 mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. RESULTS: Of the 94 patients with MVP and significant MR, 31 patients showed a TVi > .7 mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. CONCLUSIONS: Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

The value of serum metabolomics analysis in predicting the response to cardiac resynchronization therapy.

OBJECTIVE: To construct a prediction model based on metabolic profiling for predicting the response to cardiac resynchronization therapy (CRT). METHODS: Peripheral venous (PV) and coronary sinus (CS) blood samples were collected from 25 patients with heart failure (HF) at the time of CRT implantation, and PV blood samples were obtained from ten healthy controls. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). As per the clinical and echocardiographic assessment at the 6-month follow-up, the HF patients were categorized as CRT responders and non-responders. RESULTS: HF patients had altered serum metabolomic profiles that were significantly different from those of the healthy controls. Differential metabolites were also observed between CRT responders and non-responders. A prediction model for CRT response (CRT-Re) was constructed using the concentration levels of the differential metabolites, L-arginine and taurine. The optimal cutoff value of the CRT-Re model was found to be 0.343 by ROC analysis (sensitivity, 88.2%; specificity, 87.5%; Area under curve (AUC) = 0.897, P = 0.002). The concentration levels of the differential metabolites, L-arginine and lysyl-gamma-glutamate, in PV serum were significantly correlated with that in CS serum (r = 0.945 and 0.680, respectively, all P < 0.001). CONCLUSIONS: Our results suggest that serum-based metabolic profiling may be a potential complementary screening tool for predicting the outcome of CRT.

The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down-regulation and mitochondrial dynamics alteration.

The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin-related protein-1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8-week rapid atrial pacing or 4-week rapid atrial pacing and 4-week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin-II and angiotensin-II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down-regulating MCU and up-regulating DNM1L/Drp1. Cell stretching reversed the angiotensin-II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down-regulated MCU, up-regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin-II-induced cellular enlargement.

The value of left ventricular strain-volume loops in predicting response to cardiac resynchronization therapy.

BACKGROUND: Three-dimensional (3D) speckle tracking imaging (STI) allows the simultaneous assessment of left ventricular (LV) strain and volume. We aim to explore the value of LV strain-volume loops in predicting response to cardiac resynchronization therapy (CRT). METHODS: Forty heart failure (HF) patients scheduled for CRT and twenty healthy individuals were enrolled. All subjects received a 3D echocardiography and 3D STI analysis to acquire LV global and segmental principal strain (PS) and volume simultaneously. Values were plotted in a Cartesian system to construct PS-volume loop which was assessed using the two characteristics of the linear fitting curve: the slope and the coefficient of determination (R2-S/D coupling). RESULTS: HF patients at baseline showed significantly lower slope and R2-S/D coupling of all PS-volume loops than healthy subjects. As for as comparing Segmental PS-Global volume loop at baseline, Midseptal R2-S/D coupling was lower and Midlateral slope was higher in CRT responders than in non-responders. For each individual, the abnormal segmental heterogeneity of Midseptal slope and R2-S/D coupling were lower than Midlateral was observed only in responders. At follow-up, significant improvements of the Midseptal slope and R2-S/D coupling were observed in responders. Midseptal R2-S/D coupling at baseline was an independent predictor of CRT response and the cut-off value of 0.55 was recommended with sensitivity of 89% and specificity of 77%. CONCLUSIONS: Analysis of strain-volume loops could provide unique information for predicting response to CRT. Assessment of septal myocardial wasted work at baseline is helpful to improve patient selection for CRT.

Left ventricular global longitudinal strain and mechanical dispersion predict response to multipoint pacing for cardiac resynchronization therapy.

PURPOSE: To evaluate the acute effect of multipoint pacing (MPP) and search for the better baseline predictors of response to MPP for guiding patient selection. METHODS: We enrolled 46 heart failure patients scheduled for implantation of MPP-enabled cardiac resynchronization therapy (CRT) devices. An acute pacing protocol including conventional CRT and MPP pacing configurations was performed after implantation. Echocardiography was used at baseline and during pacing test, and response was defined as left ventricular (LV) end-systolic volume (ESV) reduction ≥ 15% at 6-month follow-up. RESULTS: MPP response was present in 32 (69%) patients. Responders showed significantly superior LV ejection fraction, global longitudinal peak strain (GLPS), and mechanical dispersion (MD) with MPP than with conventional CRT (all P < 0.05). Baseline GLPS (OR 1.524; 95% CI 1.031-2.251; P = 0.034) and MD (OR 1.048; 95% CI 1.016-1.081; P = 0.003) were independent predictors of MPP response in multivariate regression analysis. Both |GLPS| and MD were significantly correlated with percentage change in LVESV (▵LVESV%) at 6-month follow-up (r = 0.731 and r = 0.696, respectively; all P < 0.001). |GLPS| ≥ 5.0% combined with MD ≥ 120 ms predicted MPP response with the optimal sensitivity of 91% and specificity of 71% (AUC = 0.848, P < 0.001). CONCLUSIONS: MPP tends to be superior to conventional CRT in improving acute response. |GLPS| and MD can successfully predict response to MPP, and their combination can further improve the prediction accuracy of response.

Speckle tracking echocardiography analyses of myocardial contraction efficiency predict response for cardiac resynchronization therapy.

BACKGROUND: In patients with left ventricular (LV) dysssynchrony, contraction that doesn't fall into ejection period (LVEj) results in a waste of energy due to inappropriate contraction timing, which was now widely treated by cardiac resynchronization therapy(CRT). Myocardial Contraction Efficiency was defined as the ratio of Efficient Contraction Time (ECTR) and amplitude of efficient contraction (ECR) during LVEj against that in the entire cardiac cycle. This study prospectively investigated whether efficiency indexes could predict CRT outcome. METHODS: Our prospective pilot study including 70 CRT candidates, parameters of myocardial contraction timing and contractility were measured by speckle tracking echocardiography (STE) and efficiency indexes were calculated accordingly at baseline and at 6-month follow-up. Primary outcome events were predefined as death or HF hospitalization, and secondary outcome events were defined as all-cause death during the follow-up. 16-segement Standard deviation of time to onset strain (TTO-16SD) and time to peak strain (TTP-16SD) were included as the dyssynchrony indexes. RESULTS: According to LV end systolic volume (LVESV) and LV eject fraction(LVEF) values at 6-month follow-up, subjects were classified into responder and non-responder groups, ECR (OR 0.87, 95%CI 0.78-0.97, P < 0.05) and maximum longitudinal strain (MLS) (OR 2.22, 95%CI 1.36-3.61, P < 0.01) were the two independent predictors for CRT response, Both TTO-16SD and TTP-16SD failed to predict outcome. Patients with poorer myocardial contraction efficiency and better contractility are more likely to benefit from CRT. CONCLUSIONS: STE can evaluate left ventricular contraction efficiency and contractility to predict CRT response. When analyzing myocardial strain by STE, contraction during LVEj should be highlighted.