ABSTRACT
Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.Copyright © 2022 Elsevier Ltd
ABSTRACT
Background: Cardiac injury has been identified as an independent risk factor of mortality in COVID-19, but early recognition of severe COVID-19 illness remains challenging. Several lab parameters have been proposed to help guide clinical decisions. This study aimed to evaluate the association between troponin (TN), N-terminal pro-brain naturietic peptide (BNP), and sodium and adverse clinical outcomes in COVID-19.Methods: This retrospective single-center cohort included consecutive COVID-19 patients admitted to the George Washington University Hospital between March 2020 and May 2020. Patient demographics, cardiovascular comorbidities, and laboratory values were examined. Elevated TN and BNP were defined as >0.02 ng/mL and >150 ng/L, respectively. Primary outcomes included ICU admission and mortality. The presence of underlying cardiovascular disease (CVD) was analyzed to evaluate for relative effect on clinical outcomes. Chi-square and multinomial regression models were utilized to evaluate the association between biomarkers and clinical outcomes.Results: 290 patients were identified with a median age of 62 and the majority were male (52.4%), Black (71.3%), and had CVD risk factors (72.1%). ICU admission occurred in 88 (30.3%) while death occurred in 74 (25.5%) individuals. Patients with both an elevated TN and CVD were more likely to experience ICU admission or death (OR=2.55, p=0.017) while patients with both elevated TN and elevated BNP had markedly increased odds of ICU admission or death (OR=7.53, p<0.001). Among patients with CVD, hypernatremia (Na>145) was associated with over an eight-fold increased odds of ICU admission or death (OR=8.57, p<0.001). An isolated elevated BNP with CVD did not increase the risk of primary events.Conclusion: Among COVID-19 patients with underlying CVD, the presence of an elevated TN or hypernatremia was associated with significantly increased odds of ICU admission or death. Elevated BNP with CVD did not increase risk of events. Identifying these factors on presentation may prove helpful for early triage of high-risk patients.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (COVID-19) is linked to adverse cardiovascular outcomes in hospitalized patients but predicting the clinical course remains challenging. The purpose of this study was to examine the association between two biomarkers, troponin-I (TN) and interleukin-6 (IL-6), and cardiovascular morbidity and mortality in patients hospitalized with COVID-19. Methods: This is a retrospective single-center study of patients hospitalized with COVID-19 from March 2020 to May 2020. Elevated TN and IL-6 were defined as >0.02 ng/ml and >65.9 ng/mL respectively. The primary outcome was mortality with secondary outcomes including intensive care unit (ICU) admission and adverse cardiovascular outcomes (heart failure (HF), arrhythmia, myocardial infarction (MI), and pericarditis). Chi-squared tests and student t-tests were used for statistical analyses to examine the relationship between the presence of positive biomarkers and outcomes;p<0.05 significant. Results: In total, 150 patients were identified with the majority being African American (70%), males (55%) and an average age of 63.7 years. Patients with elevated TN had significantly increased mortality rates (36.1% vs. 19.2%, OR 2.4, p=0.021), incidence of arrhythmias (15.3% vs. 1.3%, OR 13.9, p=0.002), incidence of HF (13.9% vs. 1.3%, OR 12.4, p=0.003), and incidence of MI (13.9% vs. 1.3%, OR 12.4, p=0.003). Patients with elevated IL-6 had significantly higher mortality rates (42.7% vs. 12.0%, OR 5.5, p=<0.001), ICU admissions (50.7% vs. 18.7%, OR 4.5, p=<0.0001), incidence of arrhythmias (13.3% vs. 2.7%, OR 5.6, p=0.016), incidence of HF (12.0% vs. 2.7%, OR 5.0, p=0.028), and incidence of MI (13.3% vs. 1.3%, OR 11.4, p= 0.0048). Conclusion: Myocardial injury evidenced by elevated TN and elevated IL-6 are predictive of severe COVID-19 infections and cardiovascular complications, irrespective of race as seen in this cohort. Early detection at hospital admission and perhaps subsequent monitoring of TN and IL-6 could be beneficial in triage and to identify potential early escalation of care.