COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Portopulmonary hypertension in the current era of pulmonary hypertension management.

BACKGROUND & AIMS: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. METHODS: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. RESULTS: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). CONCLUSION: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. LAY SUMMARY: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Routes of SARS-Cov2 transmission in the intensive care unit: A multicentric prospective study.

BACKGROUND: The risk of SARS-CoV-2 transmission to health care workers in intensive care units (ICU) and the contribution of airborne and fomites to SARS-CoV-2 transmission remain unclear. To assess the rate of air and surface contamination and identify risk factors associated with this contamination in patients admitted to the ICU for acute respiratory failure due to SARS-CoV-2 pneumonia. METHODS: Prospective multicentric non-interventional study conducted from June 2020 to November 2020 in 3 French ICUs. For each enrolled patient, 3 predefined surfaces were swabbed, 2 air samples at 1 m and 3 m from the patient's mouth and face masks of 3 health care workers (HCW) were collected within the first 48 h of SARS-CoV-2 positive PCR in a respiratory sample. Droplet digital PCR and quantitative PCR were performed on different samples, respectively. RESULTS: Among 150 included patients, 5 (3.6%, 95%CI: 1.2% to 8.2%) had positive ddPCR on air samples at 1 m or 3 m. Seventy-one patients (53.3%, CI95%: 44.5% to 62.0%) had at least one surface positive. Face masks worn by HCW were positive in 6 patients (4.4%, CI: 1.6% to 9.4%). The threshold of RT-qPCR of the respiratory sample performed at inclusion (odds ratio, OR= 0.88, 95%CI: 0.83 to 0.93, p < 0.0001) and the presence of diarrhea (OR= 3.28, 95%CI: 1.09 to 9.88, p = 0.037) were significantly associated with the number of contaminated surfaces. CONCLUSION: In this study, including patients admitted to the ICU for acute respiratory failure " contact route " of transmission, i.e. through fomites, seems dominant. While presence of SARS-CoV-2 in the air is rare in this specific population, the presence of diarrhea is associated to surface contamination around Covid patients.

Clinical relevance and prognostic value of renal Doppler in acute decompensated precapillary pulmonary hypertension.

AIMS: We aim to evaluate the clinical relevance and the prognostic value of arterial and venous renal Doppler in acute decompensated precapillary pulmonary hypertension (PH). METHODS AND RESULTS: The renal resistance index (RRI) and the Doppler-derived renal venous stasis index (RVSI) were monitored at admission and on Day 3 in a prospective cohort of precapillary PH patients managed in intensive care unit for acute right heart failure (RHF). The primary composite endpoint included death, circulatory assistance, urgent transplantation, or rehospitalization for acute RHF within 90 days following inclusion. Ninety-one patients were enrolled (58% female, age 58 ± 16 years). The primary endpoint event occurred in 32 patients (33%). In univariate logistic regression analysis, variables associated with RRI higher than the median value were non-variable parameters (age and history of hypertension), congestion (right atrial pressure and renal pulse pressure), cardiac function [tricuspid annular plane systolic excursion (TAPSE) and left ventricular outflow tract- velocity time integral], systemic pressures and NT-proBNP. Variables associated with RVSI higher than the median value were congestion (high central venous pressure, right atrial pressure, and renal pulse pressure), right cardiac function (TAPSE), severe tricuspid regurgitation, and systemic pressures. Inotropic support was more frequently required in patients with high RRI (P = 0.01) or high RVSI (P = 0.003) at the time of admission. At Day 3, a RRI value <0.9 was associated with a better prognosis after adjusting to the estimated glomerular filtration rate. CONCLUSION: Renal Doppler provides additional information to assess the severity of patients admitted to the intensive care unit for acute decompensated precapillary PH.

Functional respiratory complaints among COVID-19 survivors: a prospective cohort study.

Background: Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear. Methods: We assessed the proportion and characteristics of patients with "functional respiratory complaints" (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (i.e., symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET). Findings: In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9-26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, seven out of 21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12 out of 21 patients, five out of 21 had normal CPET, three out of 21 had deconditioning and one out of 21 had evidence of uncontrolled cardiovascular disease. Interpretation: FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases.

High flow nasal oxygen therapy to avoid invasive mechanical ventilation in SARS-CoV-2 pneumonia: a retrospective study.

BACKGROUND: The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim of this study was to compare the risk of IMV between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patients. METHODS: This was a bicenter retrospective study which took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay and ventilator-free days at day 28. Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group using weighted propensity score. RESULTS: Among 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients received IMV and 46/62 (74%) in SOT group (OR 0.37 [95% CI, 0.18-0.76] p = 0.007). After weighted propensity score, HFNO was still associated with a lower rate of IMV (OR 0.31 [95% CI, 0.14-0.66] p = 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after weighted propensity score. Ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days, p = 0.005). In the HFNO group, predictive factors associated with IMV were SAPS2 score (OR 1.13 [95%CI, 1.06-1.20] p = 0.0002) and ROX index > 4.88 (OR 0.23 [95%CI, 0.008-0.64] p = 0.006). CONCLUSIONS: High flow nasal canula oxygen for ARF due to COVID-19 is associated with a lower rate of invasive mechanical ventilation.