Out-of-hospital cardiac arrest (OHCA) is a significant socioeconomic burden to society.¹ In a large trial, 50% of patients who attained stable return of spontaneous circulation (ROSC) during initial resuscitation and were transferred to the hospital for postresuscitation care achieved neurologically favorable survival.² However, refractory cardiac arrest (ie, prolonged cardiac arrest and cardiac arrest without ROSC in the field) is associated with poor clinical outcomes.³ In patients without ROSC, the odds of survival are low when transport to the hospital occurs during ongoing cardiopulmonary resuscitation (CPR), usually less than 4%.^4,5

Objectives: To elucidate the epidemiology, complication profiles, hospital outcome, and predisposing factors of CNS complications occurring during venoarterial extracorporeal membrane oxygenation in adults. Design: Retrospective analysis of the Extracorporeal Life Support Organization registry. Setting: Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers from 1992 to 2013. Patients: Patients more than 16 years old supported with a single-run of venoarterial extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: We examined 4,522 adult patients supported with venoarterial extracorporeal membrane oxygenation and included in the Extracorporeal Life Support Organization registry. Venoarterial extracorporeal membrane oxygenation was used for cardiac dysfunction in 3,005 patients (66.5%), cardiopulmonary resuscitation in 877 patients (19.4%), and respiratory failure in 640 patients (14.1%), respectively. Multivariate logistic regression was performed to identify factors independently associated with CNS injury. Neurologic complications occurred in 682 patients (15.1%), and included brain death in 358 patients (7.9%), cerebral infarction in 161 patients (3.6%), seizures in 83 patients (1.8%), and cerebral hemorrhage in 80 patients (1.8%). Multiple CNS complications in the same patient occurred in 70 cases. Hospital mortality in patients with CNS complications was 89%, compared with 57% in patients without (p < 0.001). In a multivariable model, age, pre-extracorporeal membrane oxygenation cardiac arrest, the use of inotropes on extracorporeal membrane oxygenation, and post-extracorporeal membrane oxygenation hypoglycemia were shown to be associated with CNS complications. Conclusions: Neurologic complications in adult patients on venoarterial extracorporeal membrane oxygenation support are common and associated with poor survival. Further research should focus on better understanding and management of brain/extracorporeal membrane oxygenation interaction to avoid such catastrophic complications.

Frailty may modify the risk versus benefit of various therapeutic interventions in heart failure. In this study, the authors performed a post hoc analysis of the DAPA-HF trial to examine the effica... Visual Dapagliflozin and Frailty in HFrEF. Frailty may modify the risk versus benefit of various therapeutic interventions in heart failure. In this study, the authors performed a post hoc... Background: Frailty may modify the risk−benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments. Objective: To investigate the efficacy of dapagliflozin a...

Background: Frailty is increasing in prevalence. Because patients with frailty are often perceived to have a less favorable risk/benefit profile, they may be less likely to receive new pharmacologic treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure with mildly reduced or preserved ejection fraction randomized in DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). Methods: Frailty was measured using the Rockwood cumulative deficit approach. The primary end point was time to a first worsening heart failure event or cardiovascular death. Results: Of the 6263 patients randomized, a frailty index (FI) was calculable in 6258. In total, 2354 (37.6%) patients had class 1 frailty (FI ≤0.210; ie, not frail), 2413 (38.6%) had class 2 frailty (FI 0.211–0.310; ie, more frail), and 1491 (23.8%) had class 3 frailty (FI ≥0.311; ie, most frail). Greater frailty was associated with a higher rate of the primary end point (per 100 person-years): FI class 1, 6.3 (95% CI 5.7–7.1); class 2, 8.3 (7.5–9.1); and class 3, 13.4 (12.1–14.7; P <0.001). The effect of dapagliflozin (as a hazard ratio) on the primary end point from FI class 1 to 3 was 0.85 (95% CI, 0.68–1.06), 0.89 (0.74–1.08), and 0.74 (0.61–0.91), respectively ( P _interaction =0.40). Although patients with a greater degree of frailty had worse Kansas City Cardiomyopathy Questionnaire scores at baseline, their improvement with dapagliflozin was greater than it was in patients with less frailty: placebo-corrected improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score at 4 months in FI class 1 was 0.3 (95% CI, −0.9 to 1.4); in class 2, 1.5 (0.3–2.7); and in class 3, 3.4 (1.7–5.1; P _interaction =0.021). Adverse reactions and treatment discontinuation, although more frequent in patients with a greater degree of frailty, were not more common with dapagliflozin than with placebo irrespective of frailty class. Conclusions: In DELIVER, frailty was common and associated with worse outcomes. The benefit of dapagliflozin was consistent across the range of frailty studied. The improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with a higher level of frailty. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03619213.