Cardiac arrhythmias in patients with COVID-19: Lessons from 2300 telemetric monitoring days on the intensive care unit.

BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.

Effects of different exercise modalities on cardiac dysfunction in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent disease. Physical exercise has been shown to alter disease progression in HFpEF. We examined cardiomyocyte Ca2+ homeostasis and left ventricular function in a metabolic HFpEF model in sedentary and trained rats following 8 weeks of moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT). METHODS AND RESULTS: Left ventricular in vivo function (echocardiography) and cardiomyocyte Ca2+ transients (CaTs) (Fluo-4, confocal) were compared in ZSF-1 obese (metabolic syndrome, HFpEF) and ZSF-1 lean (control) 21- and 28-week-old rats. At 21 weeks, cardiomyocytes from HFpEF rats showed prolonged Ca2+ reuptake in cytosolic and nuclear CaTs and impaired Ca2+ release kinetics in nuclear CaTs. At 28 weeks, HFpEF cardiomyocytes had depressed CaT amplitudes, decreased sarcoplasmic reticulum (SR) Ca2+ content, increased SR Ca2+ leak, and elevated diastolic [Ca2+ ] following increased pacing rate (5 Hz). In trained HFpEF rats (HIIT or MICT), cardiomyocyte SR Ca2+ leak was significantly reduced. While HIIT had no effects on the CaTs (1-5 Hz), MICT accelerated early Ca2+ release, reduced the amplitude, and prolonged the CaT without increasing diastolic [Ca2+ ] or cytosolic Ca2+ load at basal or increased pacing rate (1-5 Hz). MICT lowered pro-arrhythmogenic Ca2+ sparks and attenuated Ca2+ -wave propagation in cardiomyocytes. MICT was associated with increased stroke volume in HFpEF. CONCLUSIONS: In this metabolic rat model of HFpEF at an advanced stage, Ca2+ release was impaired under baseline conditions. HIIT and MICT differentially affected Ca2+ homeostasis with positive effects of MICT on stroke volume, end-diastolic volume, and cellular arrhythmogenicity.

Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction.

In this article, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of metabolic syndrome (MetS)-related heart failure with preserved ejection fraction (HFpEF). The prevalence of MetS-related HFpEF is rising, and atrial cardiomyopathies associated with atrial remodeling and atrial fibrillation are clinically highly relevant as atrial remodeling is an independent predictor of mortality. Studies with isolated single-cell cardiomyocytes are frequently used to corroborate and complement in vivo findings. Circulatory vessel rarefication and interstitial tissue fibrosis pose a potentially limiting factor for the successful single-cell isolation of ACMs from animal models of this disease. We have addressed this issue by employing a device capable of manually regulating the intraluminal pressure of cardiac cavities during the isolation procedure, substantially increasing the yield of morphologically and functionally intact ACMs. The acquired cells can be used in a variety of different experiments, such as cell culture and functional Calcium imaging (i.e., excitation-contraction-coupling). We provide the researcher with a step-by-step protocol, a list of optimized solutions, thorough instructions to prepare the necessary equipment, and a comprehensive troubleshooting guide. While the initial implementation of the procedure might be rather difficult, a successful adaptation will allow the reader to perform state-of-the-art ACM isolations in a rat model of MetS-related HFpEF for a broad spectrum of experiments.

Cellular mechanisms of metabolic syndrome-related atrial decompensation in a rat model of HFpEF.

Heart failure (HF) with preserved ejection fraction (HFpEF) is present in about 50% of HF patients. Atrial remodeling is common in HFpEF and associated with increased mortality. We postulate that atrial remodeling is associated with atrial dysfunction in vivo related to alterations in cardiomyocyte Calcium (Ca) signaling and remodeling. We examined atrial function in vivo and Ca transients (CaT) (Fluo4-AM, field stim) in atrial cardiomyocytes of ZSF-1 rats without (Ln; lean hypertensive) and with metabolic syndrome (Ob; obese, hypertensive, diabetic) and HFpEF. RESULTS: At 21weeks Ln showed an increased left ventricular (LV) mass and left ventricular end-diastolic pressure (LVEDP), but unchanged left atrial (LA) size and preserved atrial ejection fraction vs. wild-type (WT). CaT amplitude in atrial cardiomyocytes was increased in Ln (2.9±0.2 vs. 2.3±0.2F/F0 in WT; n=22 cells/group; p<0.05). Studying subcellular Ca release in more detail, we found that local central cytosolic CaT amplitude was increased, while subsarcolemmal CaT amplitudes remained unchanged. Moreover, Sarcoplasmic reticulum (SR) Ca content (caffeine) was preserved while Ca spark frequency and tetracaine-dependent SR Ca leak were significantly increased in Ln. Ob mice developed a HFpEF phenotype in vivo, LA area was significantly increased and atrial in vivo function was impaired, despite increased atrial CaT amplitudes in vitro (2.8±0.2; p<0.05 vs. WT). Ob cells showed alterations of the tubular network possibly contributing to the observed phenotype. CaT kinetics as well as SR Ca in Ob were not significantly different from WT, but SR Ca leak remained increased. Angiotensin II (Ang II) reduced in vitro cytosolic CaT amplitudes and let to active nuclear Ca release in Ob but not in Ln or WT. SUMMARY: In hypertensive ZSF-1 rats, a possibly compensatory increase of cytosolic CaT amplitude and increased SR Ca leak precede atrial remodeling and HFpEF. Atrial remodeling in ZSF-1 HFpEF is associated with an altered tubular network in-vitro and atrial contractile dysfunction in vivo, indicating insufficient compensation. Atrial cardiomyocyte dysfunction in vitro is induced by the addition of angiotensin II.