Scherer, Clemens

Abstract Aims Cardiogenic shock (CS) is often treated with catecholamines titrated to an adequate target mean arterial pressure (MAP) while minimizing adverse effects. We aim to assess the optimal catecholamine dose/MAP balance in heart failure-associated CS (HF-CS). Methods Patients with HF-CS were retrospectively enrolled from 16 tertiary centres in 5 European countries (2016–2021; NCT03313687). Dosage was quantified by inotropic scores (epinephrine, norepinephrine, and dobutamine). Associations of baseline and seven-day summarized dosage with intensive care unit (ICU) discharge (mixed-effects logistic regression) and 30-day mortality (Cox regression) were analysed. Potential catecholamine/MAP target ratios for optimized outcomes were assessed in models adjusted for age, sex, pH, lactate and prior resuscitation, stratified by centre. Results N = 704 patients: median age 63 years, 74% male, 34% post-resuscitation, median lactate 5.2 mmol/l. Of these, 53% were discharged from ICU, 48% died within 30 days. Higher inotropic scores independently predicted a lower probability of ICU discharge (baseline score: OR 0.78 [95%-CI 0.69–0.88]; summarized score: OR 0.46 [0.38–0.56]; both P < .001) and higher risk of 30-day mortality (baseline score: HR 1.27 [1.15–1.40], summarized score HR 1.83 [1.60–2.09]; both P < .001). A score/MAP ratio <0.403 µg/kg/min/mmHg was associated with higher ICU discharge odds (ceiling effect); a < 0.426 µg/kg/min/mmHg with lower 30-day mortality hazards (no ceiling effect). Lowering catecholamine doses by accepting reduced MAP targets was linked to better outcomes. Conclusion In HF-CS, higher catecholamine support independently associates with worse outcomes. Accepting lower blood pressure targets to reduce catecholamine dosage may improve outcomes. Validation in randomized controlled trials is urgently needed.

Background: Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is owing to fatal inflammatory responses apart from lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to nonthyroidal illness syndrome have been described. Furthermore, angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. Objective: To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients who died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFTs with the severity of the disease in a prospective cohort study. Methods: Thyroid tissue of deceased COVID-19 patients ( n = 23) was analyzed for histopathology and ACE2 expression by immunohistochemical staining. A total of 153 patients with confirmed SARS-CoV-2 were evaluated regarding TFTs and divided into a severe (intubation, intensive care treatment) and an intermediate group. Results: Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and thyrotropin (TSH) was associated significantly with deadly disease. Conclusion: The high percentage of positive ACE2 immunostaining in deceased patients compared with normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L were associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFTs is crucial in the treatment of severely ill COVID-19 patients. Trial Registration: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.