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Aims: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.
Methods and results: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.
Conclusion: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.
Aims: SARS-CoV-2 infection is associated with adverse outcomes in patients with cardiovascular disease. Here, we analyzed whether specific biomarkers predict the clinical course of COVID-19 in patients with cardiovascular comorbidities. Methods and results: We enrolled 2147 patients with SARS-CoV-2 infection which were included in the Lean European Open Survey on SARS-CoV‑2 (LEOSS)-registry from March to June 2020. Clinical data and laboratory values were collected and compared between patients with and without cardiovascular comorbidities in different clinical stages of the disease. Predictors for mortality were calculated using multivariate regression analysis. We show that patients with cardiovascular comorbidities display significantly higher markers of myocardial injury and thrombo-inflammatory activation already in the uncomplicated phase of COVID-19. In multivariate analysis, elevated levels of troponin [OR 1.54; (95% CI 1.22–1.96), p < 0.001)], IL-6 [OR 1.69 (95% CI 1.26–2.27), p < 0.013)], and CRP [OR 1.32; (95% CI 1.1–1.58), p < 0.003)] were predictors of mortality in patients with COVID-19. Conclusion: Patients with cardiovascular comorbidities show elevated markers of thrombo-inflammatory activation and myocardial injury, which predict mortality, already in the uncomplicated phase of COVID-19. Starting targeted anti-inflammatory therapy and aggressive anticoagulation already in the uncomplicated phase of the disease might improve outcomes after SARS-CoV-2 infection in patients with cardiovascular comorbidities.
Aims: Systemic inflammatory response, identified by increased total leucocyte counts, was shown to be a strong predictor of mortality after transcatheter aortic valve implantation (TAVI). Yet the mechanisms of inflammation-associated poor outcome after TAVI are unclear. Therefore, the present study aimed at investigating individual inflammatory signatures and functional heterogeneity of circulating myeloid and T-lymphocyte subsets and their impact on 1 year survival in a single-centre cohort of patients with severe aortic stenosis undergoing TAVI. Methods and results: One hundred twenty-nine consecutive patients with severe symptomatic aortic stenosis admitted for transfemoral TAVI were included. Blood samples were obtained at baseline, immediately after, and 24 h and 3 days after TAVI, and these were analysed for inflammatory and cardiac biomarkers. Myeloid and T-lymphocyte subsets were measured using flow cytometry. The inflammatory parameters were first analysed as continuous variables; and in case of association with outcome and area under receiver operating characteristic (ROC) curve (AUC) ≥ 0.6, the values were dichotomized using optimal cut-off points. Several baseline inflammatory parameters, including high-sensitivity C-reactive protein (hsCRP; HR = 1.37, 95% CI: 1.15–1.63; P < 0.0001) and IL-6 (HR = 1.02, 95% CI: 1.01–1.03; P = 0.003), lower counts of Th2 (HR = 0.95, 95% CI: 0.91–0.99; P = 0.009), and increased percentages of Th17 cells (HR = 1.19, 95% CI: 1.02–1.38; P = 0.024) were associated with 12 month all-cause mortality. Among postprocedural parameters, only increased post-TAVI counts of non-classical monocytes immediately after TAVI were predictive of outcome (HR = 1.03, 95% CI: 1.01–1.05; P = 0.003). The occurrence of SIRS criteria within 48 h post-TAVI showed no significant association with 12 month mortality (HR = 0.57, 95% CI: 0.13–2.43, P = 0.45). In multivariate analysis of discrete or dichotomized clinical and inflammatory variables, the presence of diabetes mellitus (HR = 3.50; 95% CI: 1.42–8.62; P = 0.006), low left ventricular (LV) ejection fraction (HR = 3.16; 95% CI: 1.35–7.39; P = 0.008), increased baseline hsCRP (HR = 5.22; 95% CI: 2.09–13.01; P < 0.0001), and low baseline Th2 cell counts (HR = 8.83; 95% CI: 3.02–25.80) were significant predictors of death. The prognostic value of the linear prediction score calculated of these parameters was superior to the Society of Thoracic Surgeons score (AUC: 0.88; 95% CI: 0.78–0.99 vs. 0.75; 95% CI: 0.64–0.86, respectively; P = 0.036). Finally, when analysing LV remodelling outcomes, ROC curve analysis revealed that low numbers of Tregs (P = 0.017; AUC: 0.69) and increased Th17/Treg ratio (P = 0.012; AUC: 0.70) were predictive of adverse remodelling after TAVI. Conclusions: Our findings demonstrate an association of specific pre-existing inflammatory phenotypes with increased mortality and adverse LV remodelling after TAVI. Distinct monocyte and T-cell signatures might provide additive biomarkers to improve pre-procedural risk stratification in patients referred to TAVI for severe aortic stenosis.