Rationale and design of the PRAETORIAN-COVID trial: A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease.

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2-infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.

Right heart and pulmonary vessels structure and function.

The right ventricle (RV) can be described in terms of 3 components: the inlet, the apex, and the infundibulum. In the normal adult, the RV shows an arrangement suited for pumping blood against low resistance, with a mass about one sixth that of left ventricle (LV) mass, and a larger volume than the LV. The RV is able to manage a progressive increase in the afterload by increasing contractility and remodeling. The gold standard measurement of contractility is maximal elastance (Emax), or the ratio between end-systolic pressure (ESP) and end-systolic volume (ESV), and the best measurement of afterload is arterial elastance (Ea), or the ratio between ESP and stroke volume (SV). The ratio Emax/Ea defines RV-arterial coupling. The optimal energy transfer from the RV to the pulmonary circulation is measured at Emax/Ea ratios of 1.5-2. In the presence of pulmonary hypertension, the SV/ESV ratio may be an acceptable surrogate of Emax/Ea. The right atrium (RA) has 3 anatomical components: the appendage, the venous part, and the vestibule. It is a dynamic structure having different functions: reservoir, conduit, and booster pump function. In case of increased afterload, the RA is enlarged, denoting high RA pressure, as a consequence of elevated RV diastolic pressure. RA area is a strong predictor of adverse clinical outcome in pulmonary arterial hypertension. In patients with severe pulmonary hypertension, in several congenital heart diseases, and in Eisenmenger syndrome, symptoms and prognosis are greatly dependent on RV function and its ability to adapt to a chronic increase in afterload.

Pulmonary arterial hypertension associated with a congenital heart defect: advanced medium-term medical treatment stabilizes clinical condition.

OBJECTIVE: Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication. DESIGN: The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy. RESULTS: All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 +/- 78 m (P = 0.2) and 41 +/- 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (beta = -7 m per year, P < 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P < 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 +/- 24-49 +/- 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 +/- 1090-650 +/- 444 dynes s/cm5, P = 0.7) showed no deterioration. CONCLUSION: Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.