Phenotype clustering of hospitalized high-risk patients with COVID-19 - a machine learning approach within the multicentre, multinational PCHF-COVICAV registry.

IMTRODUCTION: The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired prognosis have been identified. However, with machine learning (ML) approaches, certain phenotypes may be confined to classify the affected population and to predict outcome. This study aimed to phenotype patients using unsupervised ML technique within the International Postgraduate Course Heart Failure Registry for patients hospitalized with COVID-19 and Cardiovascular disease and/or RF (PCHF-COVICAV). MATERIAL AND METHODS: Patients from the eight centres with follow-up data available from the PCHF-COVICAV registry were included in this ML analysis (K-medoids algorithm). RESULTS: Out of 617 patients included into the prospective part of the registry, 458 [median age: 76 (IQR:65-84) years, 55% male] were analyzed and 46 baseline variables, including demographics, clinical status, comorbidities and biochemical characteristics were incorporated into the ML. Three clusters were extracted by this ML method. Cluster 1 (n = 181) represents mainly women with the least number of overall comorbidities and cardiovascular RF. Cluster 2 (n = 227) is characterized mainly by men with non-CV conditions and less severe symptoms of infection. Cluster 3 (n=50) mainly represents men with the highest prevalence of cardiac comorbidities and RF, more extensive inflammation and organ dysfunction with the highest 6-month all-cause mortality risk. CONCLUSIONS: The ML process has identified three important clinical clusters from hospitalized COVID-19 CV and/or RF patients. The cluster of males with severe CV disease, particularly HF, and multiple RF presenting with increased inflammation had a particularly poor outcome.

Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01-2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24-4.29], P < 0.001). CONCLUSIONS: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality.

Effects of echo-optimization of left ventricular assist devices on functional capacity, a randomized controlled trial.

AIMS: After the implantation of a left ventricular assist device (LVAD), many patients continue to experience exercise intolerance. VAFRACT trial evaluates the additional benefit of LVAD echo-guided optimization (EO) on functional capacity (FC), measured by cardiopulmonary exercise test (CPET), and quality of life (QoL). METHODS AND RESULTS: Twenty-seven patients were randomized in a 1:1 ratio to EO (EO group) vs. standard settings (CONTROL group) at least after 3 months from LVAD implant procedure. The optimal device speed was defined as the one that allows an intermittent aortic valve opening and a neutral position of the interventricular septum without increasing aortic or tricuspid regurgitation and preserving right ventricular function. The primary endpoint was peak oxygen uptake (VO2 peak) change after 3 months. Echo-guided optimization significantly improves VO2 peak (from 13.2 ± 2.5 to 14.2 ± 2.5 mL/kg/min; P < 0.001), oxygen pulse (from 9.75 ± 1.46 to 10.75 ± 2.2 mL; P < 0.001), CPET exercise time (from 490 ± 98 to 526 ± 116 s; P = 0.02), 6 min walk distance (from 363 ± 54 to 391 ± 52 m; P = 0.04), and QoL, using EuroQol Five Dimensions 3L (from 0.796 ± 0.1 to 0.85 ± 0.08; P < 0.001) and the Kansas City Cardiomyopathy Questionnaire (from 81.6 ± 6.9 to 84.6 ± 5.6; P = 0.025). CONCLUSIONS: Echo-guided optimization can significantly influence the FC and the QoL of LVAD patients. This procedure should represent a fundamental step in their clinical management, through the establishment of consolidated follow-up protocols. Our study may represent a starting point for a future, adequately powered clinical trial with a longer term follow-up.

The determinants of functional capacity in left ventricular assist device patients: many actors with not well defined roles.

: Improvement in hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs). However, functional capacity assessed by cardiopulmonary exercise test (CPET), following LVAD implantation, remains considerably restricted. In this review, we analyzed the current knowledge on the causes of the persistent limitation in exercise capacity in CF-LVAD patients. Limitation to exercise is multifactorial and involves: LVAD factors (fixed CF-LVAD pump speed), native cardiac factors (residual function of native left ventricle, right ventricular dysfunction, aortic valve abnormalities), comorbidities (abnormal skeletal muscle metabolism, low skeletal muscle mass, anemia), patient's characteristics (age, physical deconditioning). In addition, we emphasize the role of some potential therapeutic strategies like the increase in CF-LVAD pump speed according to the patient's activity, the echo-optimization of the device (paying attention to right ventricular function and aortic valve opening), the implementation of physical rehabilitation and the treatment of potentially reversible extracardiac factors (anemia, muscle deconditioning, obesity).

Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis.

BACKGROUND: Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM. METHODS: The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis. RESULTS: In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (P<0.0001). Long-term heart transplantation-free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank P<0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%-40%] versus 3% [0%-10%], respectively; P<0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45-7.64, P=0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ≥55% at discharge had a significant decrease in LVEF at follow-up. CONCLUSIONS: Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.

Contractile reserve in systemic sclerosis patients as a major predictor of global cardiac impairment and exercise tolerance.

Several studies have evidenced high prevalence of myocardial systolic and diastolic dysfunction among patients with systemic sclerosis (SSc). Exercise echocardiography has shown a diagnostic and prognostic role in identifying early left ventricular (LV) dysfunction in several myocardial pathological settings. The aim of our study was to evaluate early signs of LV impairment under exercise and their correlation to patient's exercise tolerance. Forty-five patients (age 60.4 ± 10.3 years) with SSc and 20 age and sex comparable controls were enrolled in the study. All patients underwent clinical evaluation, 2D echocardiography associated with Tissue Doppler and speckle tracking to evaluate LV deformation indexes, and an exercise echocardiography to evaluate left ventricle contractile reserve (LVCR) and exercise pulmonary pressures. Finally, a 6-minute walking test (6MWT) to evaluate exercise tolerance was also performed. Compared to controls, SSc patients showed an impaired diastolic function (E/E' 10.9 ± 3.7 vs 8.36 ± 2.01; p < 0.01) associated with larger left atrial dimensions (LAVI 28.4 ± 8.7 vs 19.3 ± 4.6 mL/m(2); p < 0.01). During exercise echocardiography, a reduced global longitudinal strain at peak exercise (S-GLS) was highlighted compared to controls (15.7 ± 3.6 vs 18.2 ± 2.2; p = 0.001). A S-GLS cutoff <18%, identified by ROC analysis, identified SSc patients with a reduced diastolic function, exercise tolerance at the 6MWT and higher pulmonary pressures. Our data show that in SSc patients a reduced LVCR characterizes the patients with a more extensive cardiovascular impairment in terms of LV diastolic function, pulmonary pressures and exercise tolerance. These data underline the importance of exercise echocardiography for the preclinical screening of the LV impairment in this population.