Cardiac resynchronization therapy using bi-ventricular pacing is proven effective in the management of heart failure (HF) with a wide QRS-complex. In the absence of QRS prolongation, however, device-based resynchronization is reported unsuitable. As an alternative, the present study tests a regenerative cell-based approach in the setting of narrow QRS-complex HF.

Contractile discordance exacerbates cardiac dysfunction, aggravating heart failure outcome. Dissecting the genesis of mechanical dyssynchrony would enable an early diagnosis before advanced disease.

Background The Purkinje network appears to play a pivotal role in the triggering as well as maintenance of ventricular fibrillation. Irreversible electroporation ( IRE ) using direct current has shown promise as a nonthermal ablation modality in the heart, but its ability to target and ablate the Purkinje tissue is undefined. Our aim was to investigate the potential for selective ablation of Purkinje/fascicular fibers using IRE . Methods and Results In an ex vivo Langendorff model of canine heart (n=8), direct current was delivered in a unipolar manner at various dosages from 750 to 2500 V, in 10 pulses with a 90-μs duration at a frequency of 1 Hz. The window of ventricular fibrillation vulnerability was assessed before and after delivery of electroporation energy using a shock on T-wave method. IRE consistently eradicated all Purkinje potentials at voltages between 750 and 2500 V (minimum field strength of 250-833 V/cm). The ventricular electrogram amplitude was only minimally reduced by ablation: 0.6±2.3 mV ( P=0.03). In 4 hearts after IRE delivery, ventricular fibrillation could not be reinduced. At baseline, the lower limit of vulnerability to ventricular fibrillation was 1.8±0.4 J, and the upper limit of vulnerability was 19.5±3.0 J. The window of vulnerability was 17.8±2.9 J. Delivery of electroporation energy significantly reduced the window of vulnerability to 5.7±2.9 J ( P=0.0003), with a postablation lower limit of vulnerability=7.3±2.63 J, and the upper limit of vulnerability=18.8±5.2 J. Conclusions Our study highlights that Purkinje tissue can be ablated with IRE without any evidence of underlying myocardial damage.

Background Diastolic pulmonary gradient (DPG) was proposed as a better marker of pulmonary vascular remodeling compared with pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG). The prognostic significance of DPG in patients requiring a left ventricular assist device (LVAD) remains unclear. We sought to investigate whether pre-LVAD DPG is a predictor of survival or right ventricular (RV) failure post-LVAD. Methods and Results We retrospectively reviewed 268 patients who underwent right heart catheterization before LVAD implantation from 2007 to 2017 and had pulmonary hypertension because of left heart disease. Patients were dichotomized using DPG ≥7 mm Hg, PVR ≥3 mm Hg, or TPG ≥12 mm Hg. The associations between these parameters and all-cause mortality or RV failure post LVAD were assessed with Cox proportional hazards regression and Kaplan-Meier analyses. After a mean follow-up time of 35 months, elevated DPG was associated with increased risk of RV failure (hazard ratio [HR]: 3.30; P=0.004, for DPG ≥7 versus DPG <7), whereas elevated PVR (HR 1.85, P=0.13 for PVR ≥3 versus PVR <3) or TPG (HR 1.47, P=0.35, for TPG ≥12 versus TPG <12) were not associated with the development of RV failure. Elevated DPG was not associated with mortality risk (HR 1.16, P=0.54, for DPG ≥7 versus DPG <7), whereas elevated PVR, but not TPG, was associated with higher mortality risk (HR 1.55; P=0.026, for PVR ≥3 versus PVR <3). Conclusions Among patients with pulmonary hypertension because of left heart disease requiring LVAD support, elevated DPG was associated with RV failure but not survival, while elevated PVR predicted mortality post LVAD implantation.