On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of His-SYNC

Background The His-SYNC pilot trial was the first randomized comparison between His bundle pacing in lieu of a left ventricular lead for cardiac resynchronization therapy (His-CRT) and biventricular pacing (BiV-CRT), but was limited by high rates of crossover. Objective To evaluate the results of the His-SYNC pilot trial utilizing treatment-received (TR) and per-protocol (PP) analyses. Methods The His-SYNC pilot was a multicenter, prospective, single-blinded, randomized, controlled trial comparing His-CRT vs BiV-CRT in patients meeting standard indications for CRT (eg, NYHA II–IV patients with QRS >120 ms). Crossovers were required based on prespecified criteria. The primary endpoints analyzed included improvement in QRS duration, left ventricular ejection fraction (LVEF), and freedom from cardiovascular (CV) hospitalization and mortality. Results Among 41 patients enrolled (aged 64 ± 13 years, 38% female, LVEF 28%, QRS 168 ± 18 ms), 21 were randomized to His-CRT and 20 to BiV-CRT. Crossover occurred in 48% of His-CRT and 26% of BiV-CRT. The most common reason for crossover from His-CRT was inability to correct QRS owing to nonspecific intraventricular conduction delay (n = 5). Patients treated with His-CRT demonstrated greater QRS narrowing compared to BiV (125 ± 22 ms vs 164 ± 25 ms [TR], P < .001;124 ± 19 ms vs 162 ± 24 ms [PP], P < .001). A trend toward higher echocardiographic response was also observed (80 vs 57% [TR], P = .14; 91% vs 54% [PP], P = .078). No significant differences in CV hospitalization or mortality were observed. Conclusions Patients receiving His-CRT on-treatment demonstrated superior electrical resynchronization and a trend toward higher echocardiographic response than BiV-CRT. Larger prospective studies may be justifiable with refinements in patient selection and implantation techniques to minimize crossovers

Comparing outcomes after pulmonary vein isolation in patients with systolic and diastolic heart failure

Background: The benefit of pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is well established; its efficacy in patients with heart failure preserved ejection fraction (HFpEF) is less clear. Objective: The objective of the study was to compare AF and heart failure (HF) rehospitalizations after PVI in patients with HFpEF vs HFrEF. Methods: The IBM MarketScan Database was used to identify patients undergoing PVI for AF. Patients were categorized by HF status: absence of HF, presence of HFrEF, or presence of HFpEF. Primary outcomes were HF and arrhythmia hospitalizations after PVI. Results: A total of 32,524 patients were analyzed: 27,900 with no HF (86%), 2948 with HFrEF (9%), and 1676 with HFpEF (5%). Compared with those with no HF, both patients with HFrEF and HFpEF were more likely to be hospitalized for HF (hazard ratio [HR] 7.27; P 1 year), patients with HFpEF were more likely to have HF (HR 1.30; P < .01) and arrhythmia (HR 1.19; P < .01) rehospitalizations. Conclusion: Reductions in HF and arrhythmia hospitalizations are observed early after PVI across all patients with HF, but patients with HFpEF demonstrate higher HF rehospitalization and arrhythmia recurrence in longer-term follow-up than do patients with HFrEF

Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P &lt; 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory