Comparative Propensity Matched Outcomes in Severe COVID-19 Respiratory Failure-Extracorporeal Membrane Oxygenation or Maximum Ventilation Alone.

OBJECTIVE: Does extracorporeal membrane oxygenation (ECMO) improve outcomes in ECMO-eligible patients with COVID-19 respiratory failure compared to maximum ventilation alone (MVA)? SUMMARY BACKGROUND DATA: ECMO is beneficial in severe cases of respiratory failure when mechanical ventilation is inadequate. Outcomes for ECMO-eligible COVID-19 patients on MVA have not been reported. Consequently, a direct comparison between COVID-19 patients on ECMO and those on MVA has not been established. METHODS: A total of 3406 COVID-19 patients treated at two major medical centers in Chicago were studied. One hundred ninety-five required maximum ventilatory support, and met ECMO eligibility criteria. Eighty ECMO patients were propensity matched to an equal number of MVA patients using detailed demographic, physiological, and comorbidity data. Primary outcome was survival and disposition at discharge. RESULTS: Seventy-one percent of patients were decannulated from ECMO. Mechanical ventilation was discontinued in 75% ECMO and 16% MVA patients. Twenty-five percent of patients in the ECMO arm expired, 21% while on ECMO, compared with 74% in the MVA cohort. Mortality was significantly lower across all age and BMI groups in the ECMO arm. Sixty-eight percent ECMO and 26% MVA patients were discharged from the hospital. Fewer ECMO patients required long-term rehabilitation. Major complications such as septic shock, ventilator associated pneumonia, inotropic requirements, acute liver and kidney injuries are less frequent among ECMO patients. CONCLUSIONS: ECMO-eligible patients with severe COVID-19 respiratory failure demonstrate a 3-fold improvement in survival with ECMO. They are also in a better physical state at discharge and have lower overall complication rates. As such, strong consideration should be given for ECMO when mechanical ventilatory support alone becomes insufficient in treating COVID-19 respiratory failure.

Depressed cardiac myofilament function in human diabetes mellitus.

Diabetes mellitus is associated with a distinct cardiomyopathy. Whether cardiac myofilament function is altered in human diabetes mellitus is unknown. Myocardial biopsies were obtained from seven diabetic patients and five control, nondiabetic patients undergoing coronary artery bypass surgery. Myofilament function was assessed by determination of the developed force-Ca2+ concentration relation in skinned cardiac cells from flash-frozen human biopsies. Separate control experiments revealed that flash freezing of biopsy specimens did not affect myofilament function. All patients in the diabetes mellitus cohort were classified as Type 2 diabetes mellitus patients, and most showed signs of diastolic dysfunction. Diabetes mellitus was associated with depressed myofilament function, that is, decreased Ca2+ sensitivity (29%, P < 0.05 vs. control) and a trend toward reduction of maximum Ca2+-saturated force (29%, P = 0.08 vs. control). The slope of the force-Ca2+ concentration relation (Hill coefficient) was not affected by diabetes, however. We conclude that human diabetes mellitus is associated with decreased cardiac myofilament function. Depressed cardiac myofilament Ca2+ responsiveness may underlie the decreased ventricular function characteristic of human diabetic cardiomyopathy.

Troponin I in the murine myocardium: influence on length-dependent activation and interfilament spacing.

Cyclic AMP-dependent protein kinase (PKA) targets contractile proteins, troponin-I (TnI) and myosin binding protein C (MyBP-C) in the heart and induces a decrease in myofilament Ca2+ sensitivity. Yet, the effect of sarcomere length (SL) change on Ca2+ sensitivity (length-dependent activation: LDA) following PKA-dependent phosphorylation is not clear. To clarify the role of PKA-dependent phosphorylation of TnI and MyBP-C on LDA in the heart, we examined LDA in skinned myocytes from a non-transgenic (NTG) and a transgenic murine model in which the native cardiac isoform (cTnI) was completely replaced by the slow skeletal isoform of TnI (ssTnI-TG) lacking the phosphorylation sites for PKA, while retaining PKA sites on MyBP-C. In NTG myocytes, PKA treatment decreased Ca2+ sensitivity at each SL, but enhanced the impact of SL change on Ca2+ sensitivity. Despite a greater sensitivity to Ca2+ and a reduction in LDA, neither Ca2+ responsiveness nor LDA was affected by PKA treatment in ssTnI-TG myocytes. To determine whether the above observations could be explained by the lateral separation between thick and thin filaments, as suggested by others, we measured interfilament spacing by X-ray diffraction as a function of SL in skinned cardiac trabeculae in the passive state from both NTG and ssTnI-TG models before and following treatment with PKA. Phosphorylation by PKA increased lattice spacing at every SL in NTG trabeculae. However, the relationship between SL and myofilament lattice spacing in ssTnI-TG was markedly shifted downward to an overall decreased myofilament lattice spacing following PKA treatment. We conclude: (1) PKA-dependent phosphorylation enhances length-dependent activation in NTG hearts; (2) replacement of native TnI with ssTnI increases Ca2+ sensitivity of tension but reduces length-dependent activation; (3) MyBP-C phosphorylation by PKA does not alter calcium responsiveness and induces a decrease in myofilament lattice spacing at all sarcomere lengths and (4) length-dependent activation in the heart cannot be entirely explained by alterations in myofilament lattice spacing.