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Conventional right ventricular (RV) pacing, particularly RV apical pacing, can have deleterious effects on cardiac function. Long-term RV apical pacing has been associated with increased risk of atrial fibrillation, hospitalization for heart failure, pacing-induced cardiomyopathy and associated death. His bundle pacing (HBP) results in physiological ventricular activation and has generated tremendous research interest and enthusiasm. By stimulating the His–Purkinje network directly, HBP results in synchronized ventricular activation, which might translate into improved clinical outcomes compared with dyssynchronous ventricular activation with RV apical pacing. HBP can also overcome bundle branch block patterns, and data are accumulating on the benefit of HBP for cardiac resynchronization therapy. In this Review, we summarize the anatomy of the His bundle and early clinical observations, implantation techniques and available outcome data associated with permanent HBP. We also highlight the challenges with HBP and the need for additional tools and more randomized data before widespread application of permanent HBP.

Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18–75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36–73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6–30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3–67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7–59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. National Heart, Lung, and Blood Institute.

In a randomized trial, patients with out-of-hospital cardiac arrest who received extracorporeal CPR and those who received conventional CPR had similar results for survival and favorable neurologic outcomes.

Current recommendations for a prophylactic (primary prevention) implantable cardioverter defibrillator (ICD) in patients with both ischemic and nonischemic heart failure with reduced ejection fraction (HFrEF) originate from clinical trials conducted in selected patients over 20 years ago that showed an overall statistically significant survival benefit associated with a primary prevention ICD in the range of 23%-34%. The recent introduction of angiotensin receptor–neprilysin inhibitors [ARNI] and sodium glucose co-transporter 2 inhibitors [SGLT2i]) was shown to further reduce the risk of sudden cardiac death (SCD) in patients with HFrEF. Thus, there is an unmet need appropriately designed comparative effectiveness clinical trials aimed to reassess the survival benefit of a primary prevention ICD in contemporary patients with HFrEF. The comparative effectiveness of ICD vs non-ICD therapy in contemporary heart failure patients at a low risk for arrhythmic death (CONTEMP-ICD) trial is a prospective, multicenter, open-label, randomized-controlled trial; enrolling 3,290 participants with HFrEF who are treated with optimal stable GDMT and are eligible for a primary prevention ICD, but have a lower predicted risk of life-threatening ventricular tachyarrhythmia (VTA) than nonarrhythmic mortality. Enrolled participants will be randomized to non-ICD vs ICD treatment arms and will be followed over an average period of 3.5 years. The specific aims of the proposed clinical trial are to: (1) Compare the risk of all-cause mortality of non-ICD vs ICD in HFrEF patients who have a lower predicted risk of VTA than nonarrhythmic mortality per the MADIT-ICD Benefit Score; (2) Evaluate whether non-ICD vs ICD is associated with improved survival free of major CV events in patients with HFrEF who are at a lower predicted arrhythmic risk; (3) Assess healthcare utilization and quality of life implications of non-ICD vs ICD management approaches in HFrEF patients who are at a lower predicted arrhythmic risk; and (4) Determine the effect of non-ICD vs ICD management on all-cause mortality in prespecified subgroups. We hypothesize that, in patients with HFrEF who are at a lower predicted arrhythmic risk, non-ICD vs ICD is noninferior with respect to the primary endpoint of all-cause mortality and superior with respect to the secondary endpoint of survival free of major CV events. NCT06543446; https://contemp-icd.org.

In a randomized trial involving 8014 patients with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than placebo but not a higher rate of survival with a favorable neurologic outcome.