Impaired glucose metabolism in patients with diabetes, prediabetes, and obesity is associated with severe COVID-19.

BACKGROUND: Identification of risk factors of severe coronavirus disease 2019 (COVID-19) is critical for improving therapies and understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. We analyzed 184 patients hospitalized for COVID-19 in Livingston, New Jersey for clinical characteristics associated with severe disease. The majority of patients with COVID-19 had diabetes mellitus (DM) (62.0%), Pre-DM (23.9%) with elevated fasting blood glucose (FBG), or a body mass index >30 with normal hemoglobin A1c (HbA1C) (4.3%). SARS-CoV-2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty-four patients required intubation, which occurred significantly more often in patients with DM as compared with non-diabetics. Severe COVID-19 occurs in the presence of impaired glucose metabolism in patients, including those with DM, preDM, and obesity. COVID-19 is associated with elevated FBG and several patients presented with new onset DM or in DKA. The association of dysregulated glucose metabolism and severe COVID-19 suggests that SARS-CoV-2 pathogenesis involves a novel interplay with glucose metabolism. Exploration of pathways by which SARS-CoV-2 interacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies.

Retrograde buddy wire technique for coronary sinus lead placement--an approach to overcome coronary vein angulation.

Implantation of a left ventricular pacing lead via the coronary sinus to deliver cardiac resynchronization therapy has become standard therapy for patients with New York Heart Association (NYHA) Class III or IV heart failure and significant intraventricular conduction delay. Biventricular pacing has been shown to provide both symptomatic and mortality benefit in appropriately selected patients. There is significant variability in the anatomy of the coronary sinus and the epicardial coronary venous system. Although a suitable candidate vein may be identified during coronary venography, efforts toward successful guidewire placement or lead placement may be hampered by anatomic obstacles. In this case report, we provide a solution to overcome severe tortuosity encountered at the vein-coronary sinus junction and angulation of the proximal vein. The use of a second coronary sinus sheath and a retrogradely placed guidewire may overcome this anatomic obstacle of vessel tortuosity, when placement by other means has proven unsuccessful.

Adenosine-insensitive focal atrial tachycardia: evidence for de novo micro-re-entry in the human atrium.

OBJECTIVES: The purpose of this work was to describe the entity and mechanism of adenosine-insensitive focal atrial tachycardia (AT). BACKGROUND: The majority of regular focal ATs demonstrate properties consistent with triggered activity, including termination by adenosine. Less commonly, AT may be due to enhanced automaticity, which is transiently suppressed by adenosine. Small re-entrant circuits may also give rise to focal AT, but limited data exist regarding this entity as a de novo arrhythmia in the human atrium. METHODS: Eighty cases of focal AT were mapped in the electrophysiology laboratory and challenged with adenosine. Adenosine-sensitive and -insensitive groups were compared with regard to demographics, anatomical distribution, and electrogram characteristics at the tachycardia origin. RESULTS: In response to adenosine, termination occurred in 67 cases (84%), transient suppression in 5 (6%), 6 were insensitive (8%), and 2 exhibited nonspecific responses. Adenosine-insensitive AT arose near the pulmonary vein ostia (4) and from the right atrium (2), whereas adenosine-sensitive AT arose from a wide distribution in both atria. Electrograms at the site of origin for adenosine-insensitive AT were highly fractionated, with longer durations and lower amplitudes compared with AT that terminated or was transiently suppressed. The electrograms at the origin of adenosine-insensitive ATs comprised 22% to 69% of the tachycardia cycle length, compared with 4% to 21% for adenosine-sensitive ATs. In 3 adenosine-insensitive ATs, entrainment was demonstrated with post-pacing intervals equivalent to the tachycardia cycle length. CONCLUSIONS: The characteristics of adenosine-insensitive focal AT differ from adenosine-sensitive AT and are consistent with small re-entrant circuits. These data provide evidence that focal re-entry is a mechanism of AT and has an electropharmacologic profile that differs from AT due to automaticity and triggered activity.

Cooperative activation in cardiac muscle: impact of sarcomere length.

This study was undertaken to determine the impact of sarcomere length (SL) on the level of cooperative activation of the cardiac myofilament at physiological [Mg2+]. Active force development was measured in skinned rat cardiac trabeculae as a function of free [Ca2+] at five SLs (1.85-2.25 microm; 1 mM free [Mg2+]; 15 degrees C). Only muscle preparations with minimal force rundown during the entire protocol were included in the analysis (average 7.2 +/- 1.7%). Median SL was measured by on-line computer video micrometry and controlled within 0.01 microm. Care was taken to ensure a sufficient number of data points in the steep portion of the [Ca2+]-force relationship at every SL to allow for accurate fit of the data to a modified Hill equation. Multiple linear regression analysis of the fit parameters revealed that both maximum, Ca2+-saturated force and Ca2+ sensitivity were a significant function of SL (P < 0.001), whereas the level of cooperativity did not depend on SL (P = 0.2). Further analysis of the [Ca2+]-force relationships revealed a marked asymmetry that, also, was not affected by SL (P = 0.2-0.6). Finally, we found that the level of cooperativity in isolated skinned myocardium was comparable to that reported for intact, nonskinned myocardium. Our results suggest that an increase in SL induces an increase in the Ca2+ responsiveness of the cardiac sarcomere without affecting the level of cooperativity.