Severe Covid-19 and acute pulmonary hypertension: 24-month follow-up regarding mortality and relationship to initial echocardiographic findings and biomarkers.

INTRODUCTION: Critically ill Covid-19 patients are likely to develop the sequence of acute pulmonary hypertension (aPH), right ventricular strain, and eventually right ventricular failure due to currently known pathophysiology (endothelial inflammation plus thrombo-embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. Furthermore, an in-hospital trans-thoracic echocardiography (TTE) diagnosis of aPH is associated with a substantially increased risk of early mortality. The aim of this retrospective observational follow-up study was to explore the mortality during the 1-24-month period following the TTE diagnosis of aPH in the intensive care unit (ICU). METHODS: A previously reported cohort of 67 ICU-treated Covid-19 patients underwent an electronic medical chart-based follow-up 24 months after the ICU TTE. Apart from the influence of aPH versus non-aPH on mortality, several TTE parameters were analyzed by the Kaplan-Meier survival plot technique (K-M). The influence of biomarkers for heart failure (NTproBNP) and myocardial injury (Troponin-T), taken at the time of the ICU TTE investigation, was analyzed using receiver-operator characteristics curve (ROC) analysis. RESULTS: The overall mortality at the 24-month follow-up was 61.5% and 12.8% in group aPH and group non-aPH, respectively. An increased relative mortality risk continued to be present in aPH patients (14.3%) compared to non-aPH patients (5.6%) during the 1-24-month period. The easily determined parameter of a tricuspid valve regurgitation, allowing a measurement of a systolic pulmonary artery pressure (regardless of magnitude), was associated with a similar K-M outcome as the generally accepted diagnostic criteria for aPH (systolic pulmonary artery pressure >35 mmHg). The biomarker values of NTproBNP and Troponin-T at the time of the TTE did not result in any clinically useful ROC analysis data. CONCLUSION: The mortality risk was increased up to 24 months after the initial examination in ICU-treated Covid-19 patients with a TTE diagnosis of aPH, compared to non-aPH patients. Certain individual TTE parameters were able to discriminate 24-month risk of morality.

Acute pulmonary hypertension and short-term outcomes in severe Covid-19 patients needing intensive care.

INTRODUCTION: Critically ill Covid-19 pneumonia patients are likely to develop the sequence of acute pulmonary hypertension, right ventricular (RV) strain, and eventually RV failure due to known pathophysiology (endothelial inflammation plus thrombo-embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. This study aimed to investigate the occurrence of acute pulmonary hypertension (aPH) as per established trans-thoracic echocardiography (TTE) criteria in Covid-19 patients receiving intensive care and to explore whether short-term outcomes are affected by the presence of aPH. METHODS: Medical records were reviewed for patients treated in the intensive care units at a tertiary university hospital over a month. The presence of aPH on the TTE was noted, and plasma NTproBNP and troponin were measured as markers of cardiac failure and myocardial injury, respectively. Follow-up data were collected 21 d after the performance of TTE. RESULTS: In total, 26 of 67 patients (39%) had an assessed systolic pulmonary artery pressure of > 35 mmHg (group aPH), meeting the TTE definition of aPH. NTproBNP levels (median [range]: 1430 [102-30 300] vs. 470 [45-29 600] ng L-1 ; P = .0007), troponin T levels (63 [22-352] vs. 15 [5-407] ng L-1 ; P = .0002), and the 21-d mortality rate (46% vs. 7%; P < .001) were substantially higher in patients with aPH compared to patients not meeting aPH criteria. CONCLUSION: TTE-defined acute pulmonary hypertension was frequently observed in severely ill Covid-19 patients. Furthermore, aPH was linked to biomarker-defined myocardial injury and cardiac failure, as well as an almost sevenfold increase in 21-d mortality.

Thromboembolism, Hypercoagulopathy, and Antiphospholipid Antibodies in Critically Ill Coronavirus Disease 2019 Patients: A Before and After Study of Enhanced Anticoagulation.

To determine the prevalence of thrombotic events, functional coagulation tests, inflammatory biomarkers, and antiphospholipid antibodies before and after enhanced anticoagulation in critically ill coronavirus disease 2019 patients. DESIGN: Retrospective. SETTING: Tertiary intensive care unit. PATIENTS: Two cross-sectional cohorts of ICU-treated coronavirus disease 2019 patients were included before (cohort 1, n = 12) and after (cohort 2, n = 14) enhanced prophylactic anticoagulation strategy. INTERVENTIONS: Before and after study of enhanced anticoagulation. MEASUREMENTS AND MAIN RESULTS: Thromboelastometry point-of-care coagulation tests were performed by thromboelastography (Tem International GmbH, Munich, Germany), standard blood tests were extracted from patient charts, and presence of antiphospholipid antibodies in plasma was measured. All patients were males on mechanical ventilation. In cohort 1 (low-molecular-weight heparin dose: 129 ± 53 U/kg/24 hr), 50% had pulmonary embolism, and thromboelastography analysis revealed hypercoagulation in a majority of patients and greater than 80% had detectable antiphospholipid antibodies. In the second cohort (enhanced low-molecular-weight heparin dose: 200 ± 82 U/kg/24 hr; p = 0.04 vs cohort 1), we found a nonsignificantly lower prevalence of pulmonary embolism (21%; p = 0.22), lower fibrinogen (6.3 ± 2.5 vs 8.7 ± 2.0; p = 0.02), reduced fibrinogen-dependent thromboelastography (p < 0.001), and lower inflammatory markers. CONCLUSIONS: In these two cross-sectional cohorts of ICU-treated coronavirus disease 2019 patients, thromboembolic complications, hypercoagulation, and antiphospholipid antibodies were common. A more aggressive anticoagulation regime was associated with a reduction in inflammatory biomarkers including plasma fibrinogen and a reduction in fibrinogen-dependent hypercoagulation, as indicated by thromboelastography analyses.