This study demonstrates that both the initial portion of the QT interval (QTa) and the entire QT interval (QTe) are useful since QTa is more prolonged than QTe at increasing cycle lengths, and thus includes most of the heart rate dependency of ventricular repolarization. In normal subjects, both the QTc and the long-term relationship between ventricular repolarization and heart rate are affected by gender. The differences in QTa and QTe duration between males and females are more marked at long cycle lengths and disappear at short cycle lengths. Finally, this study also proves the clinical feasibility of assessing the long-term relationship between ventricular repolarization and heart rate by utilizing the automatic measurement of the QT interval from 24-h Holter recordings.

COVID-19 infection may lead to an Acute Respiratory Distress Syndrome where severe gas exchange derangements may be associated, at least in the early stages, only with minor pulmonary infiltrates. This suggests that the shunt associated to the gasless lung parenchyma is not sufficient to explain CARDS hypoxemia. We designed an algorithm (VentriQlar), based on the same conceptual grounds described by J.B West in 1969. We set 499 ventilation-perfusion (VA/Q) compartments and, after calculating their blood composition (PO2, PCO2 and pH), we randomly chose 106 combinations of five parameters controlling a bimodal distribution of blood flow. The solutions were accepted if the predicted PaO2 and PaCO2 were within 10% of the patient's values. We assumed that shunt fraction equaled the fraction of non-aerated lung tissue at the CT quantitative analysis. Five critically-ill patients later deceased were studied. The PaO2/FiO2 was 91.1±18.6 mmHg and PaCO2 69.0±16.1 mmHg. Cardiac output was 9.58±0.99 l/min. The fraction of non-aerated tissue was 0.33±0.06. The model showed that a large fraction of the blood flow was likely distributed in regions with very low VA/Q (Qmean=0.06±0.02) and a smaller fraction in regions with moderately high VA/Q. Overall LogSD, Q was 1.66 ± 0.14, suggestive of high VA/Q inequality. Data suggest that shunt alone cannot completely account for the observed hypoxemia and a significant VA/Q inequality must be present in COVID-19. The high cardiac output and the extensive microthrombosis later found in the autopsy further support the hypothesis of a pathological perfusion of non/poorly ventilated lung tissue.

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