OBJECTIVEAlthough intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports of cognitive impairment due to severe hypoglycemia have been highly variable. It was hypothesized that recurrent moderate hypoglycemia preconditions the brain and protects against damage caused by severe hypoglycemia.RESEARCH DESIGN AND METHODSNine-week-old male Sprague-Dawley rats were subjected to either 3 consecutive days of recurrent moderate (25–40 mg/dl) hypoglycemia (RH) or saline injections. On the fourth day, rats were subjected to a hyperinsulinemic (0.2 units · kg−1 · min−1) severe hypoglycemic (∼11 mg/dl) clamp for 60 or 90 min. Neuronal damage was subsequently assessed by hematoxylin-eosin and Fluoro-Jade B staining. The functional significance of severe hypoglycemia–induced brain damage was evaluated by motor and cognitive testing.RESULTSSevere hypoglycemia induced brain damage and striking deficits in spatial learning and memory. Rats subjected to recurrent moderate hypoglycemia had 62–74% less brain cell death and were protected from most of these cognitive disturbances.CONCLUSIONSAntecedent recurrent moderate hypoglycemia preconditioned the brain and markedly limited both the extent of severe hypoglycemia–induced neuronal damage and associated cognitive impairment. In conclusion, changes brought about by recurrent moderate hypoglycemia can be viewed, paradoxically, as providing a beneficial adaptive response in that there is mitigation against severe hypoglycemia–induced brain damage and cognitive dysfunction.

Background Coronavirus Disease 2019 (COVID-19) results in increased inflammatory markers previously associated with atrial arrhythmias. However, little is known about their incidence or specificity in COVID-19, or their association with outcomes. We determined the incidence, predictors and outcomes of atrial fibrillation or flutter (AF/AFL) in patients hospitalized with COVID-19, or hospitalized with Influenza. Methods This is a retrospective analysis of 3,970 patients admitted with PCR-positive COVID-19 between 2/4/2020-4/22/2020 with manual review performed of 1,110. The comparator arm included 1,420 patients with influenza hospitalized between 1/1/2017-1/1/2020. Results Among 3970 inpatients with COVID-19, the incidence of AF/AFL was 10% (N=375) and in patients without a history of atrial arrhythmias, 4% (N=146). Patients with new-onset AF/AFL were older with increased inflammatory markers including Interleukin-6 (93 vs 68 pg/ml, P<0.01), and more myocardial injury (Troponin-I: 0.2 vs 0.06ng/ml, P<0.01). AF/AFL were associated with increased mortality (46% vs 26%, P<0.01). Manual review captured a somewhat higher incidence of AF/AFL (13%, N=140). Compared to inpatients with COVID-19, patients with Influenza (N=1420) had similar rates of AF/AFL (12%, n=163) but lower mortality. The presence of AF/AFL correlated with similarly increased mortality in both COVID-19 (RR 1.77) and Influenza (RR 1.78). Conclusions AF/AFL occurs in a subset of patients hospitalized with either COVID-19 or Influenza, and is associated with inflammation and disease severity in both infections. The incidence and associated increase in mortality in both cohorts suggests that AF/AFL in not specific to COVID-19, but is rather a generalized response to the systemic inflammation of severe viral illnesses.

Introduction: Recent studies have described several cardiovascular manifestations of COVID-19 including myocardial ischemia, myocarditis, thromboembolism, and malignant arrhythmias. However, to our knowledge, syncope in COVID-19 patients has not been systematically evaluated. We sought to characterize syncope and/or presyncope in COVID-19. Methods: This is a retrospective analysis of consecutive patients hospitalized with laboratory-confirmed COVID-19 with either syncope or presyncope. This "study" group (n = 37) was compared with an age and gender-matched cohort of patients without syncope ("control") (n = 40). Syncope was attributed to various categories. We compared telemetry data, treatments received, and clinical outcomes between the two groups. Results: Among 1000 COVID-19 patients admitted to the Mount Sinai Hospital, the incidence of syncope/presyncope was 3.7%. The median age of the entire cohort was 69 years (range 26-89+ years) and 55% were men. Major comorbidities included hypertension, diabetes, and coronary artery disease. Syncopal episodes were categorized as (a) unspecified in 59.4% patients, (b) neurocardiogenic in 15.6% patients, (c) hypotensive in 12.5% patients, and (d) cardiopulmonary in 3.1% patients with fall versus syncope and seizure versus syncope in 2 of 32 (6.3%) and 1 of 33 (3.1%) patients, respectively. Compared with the "control" group, there were no significant differences in both admission and peak blood levels of d-dimer, troponin-I, and CRP in the "study" group. Additionally, there were no differences in arrhythmias or death between both groups. Conclusions: Syncope/presyncope in patients hospitalized with COVID-19 is uncommon and is infrequently associated with a cardiac etiology or associated with adverse outcomes compared to those who do not present with these symptoms.

IMPORTANCEEarly rhythm control of atrial fibrillation (AF) with either antiarrhythmic drugs (AADs) or catheter ablation has been reported to improve cardiovascular outcomes compared with usual care; however, the optimal therapeutic modality to achieve early rhythm control is unclear.OBJECTIVE To assess the safety and efficacy of AF ablation as first-line therapy when compared with AADs in patients with paroxysmal AF.

Background - Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias. However, little is known about these arrhythmias - their frequency, the underlying mechanisms, and their impact on mortality. Methods - We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19, were receiving continuous telemetric ECG monitoring, and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, we compared a primary composite endpoint of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrio-ventricular block. Results - Among 800 COVID-19 patients at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring and either died (52) or were discharged (88). The median (IQR) age was 61 years (48 - 74); 73% men; and ethnicity was Caucasian in 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared to discharged patients, those who died had elevated peak troponin I levels (0.27 vs 0.02 ng/mL), and more primary endpoint events (17% vs 4%, p = 0.01), a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event. Conclusions - Hospitalized COVID-19 patients who die experience malignant cardiac arrhythmias more often than those surviving to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.

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Aims We studied the extent/area of electrical pulmonary vein isolation (PVI) after either pulsed field ablation (PFA) using a pentaspline catheter or thermal ablation technologies. Methods and results In a clinical trial (NCT03714178), paroxysmal atrial fibrillation (PAF) patients underwent PVI with a multi-electrode pentaspline PFA catheter using a biphasic waveform, and after 75 days, detailed voltage maps were created during protocol-specified remapping studies. Comparative voltage mapping data were retrospectively collected from consecutive PAF patients who (i) underwent PVI using thermal energy, (ii) underwent reablation for recurrence, and (iii) had durably isolated PVs. The left and right PV antral isolation areas and non-ablated posterior wall were quantified. There were 20 patients with durable PVI in the PFA cohort, and 39 in the thermal ablation cohort [29 radiofrequency ablation (RFA), 6 cryoballoon, and 4 visually guided laser balloon]. Pulsed field ablation patients were younger with shorter follow-up. Left atrial diameter and ventricular systolic function were preserved in both cohorts. There was no significant difference between the PFA and thermal ablation cohorts in either the left- and right-sided PV isolation areas, or the non-ablated posterior wall area. The right superior PV isolation area was smaller with PFA than RFA, but this disappeared after propensity score matching. Notch-like normal voltage areas were seen at the posterior aspect of the carina in the balloon sub-cohort, but not the PFA or RFA cohorts. Conclusion Catheter-based PVI with the pentaspline PFA catheter creates chronic PV antral isolation areas as encompassing as thermal energy ablation.

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