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Intro: Recent World Symposium of Pulmonary Hypertension (WSPH) Group 1 data indicate significant racial and ethnic disparities in disease severity and mortality. It is unclear if these differences extend to other forms of PH and if they are a reflection of comorbidities. The PVDOMICS program incorporates deep phenotyping across all WSPH groups allowing for a first-time side-by-side comparison. The aims of this study are to evaluate inter-racial/ethnic factors of disease severity and comorbidities among patients with PH. Methods/Results: Participants in PVDOMICS prospectively underwent comprehensive testing for echocardiography, PFT, chest imaging, 6-minute walk, cardiac MRI, and hemodynamics with provocation. WSPH group assignment was assessed according to guideline recommendations. Race and ethnicity were self-reported. Statistical testing and sample sizes are described in the Table . In 692 PH participants, Non-Hispanic whites (NHW) were older and more often male than non-Hispanic African American (AA) and Hispanic patients. WSPH Group 1 was less but Groups 4 and 5 more common in AA than NHW. There were no inter-race/ethnicity differences in the percent of PH patients on PH therapy (range 53-63%, p=0.23). Comorbidities such as diabetes and lung disease were more common in AA vs. NHW. Hispanics showed lower left atrial (LA) volume on echo, LA filling pressures with exercise, as well as increased cardiac index relative to NHW. Right ventricular function on cardiac MRI was similar between groups ( Table ). When WSPH Group 1 was analyzed separately, inter-racial/ethnic comparisons were generally similar. Conclusions: Significant inter-racial/ethnic differences are evident across all WSPH groups. Comorbidities appear to drive part of the differences among AA patients while Hispanic patients exhibit factors that may prove beneficial. How these differences contribute to varying disease risk and outcomes across race and ethnicity remain to be seen.

Introduction: Previous reports have shown that atrial and ventricular arrhythmias (VA) are common in all forms of pulmonary hypertension (PH) with prevalence of supraventricular arrhythmias ranging from 13-25% and VA 27%. Arrhythmias are also associated with clinical worsening events. Reports have limited numbers of patients with a variety of forms of PH and limited data comparing the prevalence of atrial arrhythmias across WSPH groups and whether advancing age, WHO FC, echocardiographic, exercise capacity and hemodynamic patterns are associated with a higher prevalence of atrial arrhythmias. Methods: As part of the PVDOMICS program, we enrolled 1195 PH participants, controls and PH comparators and prospectively collected electrocardiograms (ECGs) at enrollment for 1147 of them. Comparisons across participants with and without atrial fibrillation/atrial flutter (afib/flutter) used analysis of variance (ANOVA) or Kruskal-Wallis test in continuous variables based on distribution with statistics presented as mean + SD or median [P25, P75] respectively. Pearson’s chi-square test was used for categorical variables. Results: Of 732 PH participants (467F) who had ECGs available at baseline, 527 (72.0%) were in normal sinus rhythm and 62 had afib/flutter (8.5%). Afib/flutter participants were older (75 + 8 vs 57 + 14 years; p<0.001), most commonly in WSPH group 2 (28.1%) vs. WSPH 1 (3.3%), WSPH 3(6.5%) and WSPH group 4 (3.7%), had predominantly WHO FC II/III symptoms (89.5%), higher RAP (12.6 + 5 vs.7.8 + 5mmHg; p<0.001) and PCWPm (17.8 + 5.8 vs. 12.3 + 6.2mmHg; p<0.001) and lower CO (4.3+ 1.5 vs. 5.2 +1.8L/min;p<0.001). Participants with afib/flutter had lower 6MWD 277 + 117 vs.356 + 134meters (p<0.001) than PH participants without. Echocardiography demonstrated increase in LA volume index (mL/m2), RA volume (mL) and tricuspid regurgitation severity with reduced TAPSE and LVEF (54 + 10 vs. 61 + 10%;p<0.001). ProBNP was higher in afib/flutter participants 2029 [1073, 2964] vs.268 [100, 1074]pg/ml; P<0.001) Conclusions: In this analysis of atrial arrhythmias in a large cohort of PH participants across all WSPH groups, afib/flutter was present most often in older WSPH group 2 patients who demonstrated clinical and hemodynamic features of worse heart failure.

Background: Black patients have higher rates of hospitalization for acute heart failure than other race/ethnic groups. We sought to determine whether diuretic efficiency is associated with racial differences in risk for rehospitalization after acute heart failure. Methods: A post hoc analysis was performed on 721 subjects (age, 68±13 years; 22% black) enrolled in 3 acute heart failure clinical trials: ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure), DOSE-AHF (Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure), and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Repeated-measures ANOVA was used to test for a race×time effect on measures of decongestion. Diuretic efficiency was calculated as net fluid balance per total furosemide equivalents. In a subset of subjects, Cox regression was used to examine the association between race and rehospitalization according to plasma renin activity (PRA). Results: Compared with nonblack patients, black patients were younger and more likely to have nonischemic heart failure. During the first 72 to 96 hours, there was greater fluid loss ( P =0.001), decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide; P =0.002), and lower levels of PRA ( P <0.0001) in black patients. Diuretic efficiency was higher in black than in nonblack patients (403 [interquartile range, 221–795] versus 325 [interquartile range, 154–698]; P =0.014). However, adjustment for baseline PRA attenuated the association between black race and diuretic efficiency. Over a median follow-up of 68 (interquartile range, 56–177) days, there was an increased risk of all-cause and heart failure–specific rehospitalization in nonblack patients with increasing levels of PRA, while the risk of rehospitalization was relatively constant across levels of PRA in black patients. Conclusions: Higher diuretic efficiency in black patients with acute heart failure may be related to racial differences in activity of the renin-angiotensin-aldosterone system.

Background: Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension. Methods: Subjects enrolled in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) program undergo an extensive invasive hemodynamic evaluation that includes repeated measurements at rest and during several provocative physiological challenges. It is a National Institutes of Health/National Heart, Lung, and Blood Institute initiative to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics. At a subset of centers, participants also undergo an invasive cardiopulmonary exercise test to assess changes in hemodynamics and gas exchange during exercise. Conclusions: When coupled with other physiological testing and blood -omic analyses involved in the PVDOMICS study, the comprehensive right heart catheterization protocol described here holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups. This article will describe the methods applied for invasive hemodynamic characterization in the PVDOMICS program. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02980887.

Abstract Deep learning (DL) is a branch of machine learning (ML) showing increasing promise in medicine, to assist in data classification, novel disease phenotyping and complex decision making. Deep learning is a form of ML typically implemented via multi-layered neural networks. Deep learning has accelerated by recent advances in computer hardware and algorithms and is increasingly applied in e-commerce, finance, and voice and image recognition to learn and classify complex datasets. The current medical literature shows both strengths and limitations of DL. Strengths of DL include its ability to automate medical image interpretation, enhance clinical decision-making, identify novel phenotypes, and select better treatment pathways in complex diseases. Deep learning may be well-suited to cardiovascular medicine in which haemodynamic and electrophysiological indices are increasingly captured on a continuous basis by wearable devices as well as image segmentation in cardiac imaging. However, DL also has significant weaknesses including difficulties in interpreting its models (the ‘black-box’ criticism), its need for extensive adjudicated (‘labelled’) data in training, lack of standardization in design, lack of data-efficiency in training, limited applicability to clinical trials, and other factors. Thus, the optimal clinical application of DL requires careful formulation of solvable problems, selection of most appropriate DL algorithms and data, and balanced interpretation of results. This review synthesizes the current state of DL for cardiovascular clinicians and investigators, and provides technical context to appreciate the promise, pitfalls, near-term challenges, and opportunities for this exciting new area.

Purpose: Psychosocial assessment of patients comprises an important element in the selection process of appropriate candidates for left ventricular assist device (LVAD) implantation. We sought to determine the association of the well-validated psychosocial assessment of candidates for transplantation (PACT) scale to clinical outcomes post-LVAD implantation. Materials and Methods: The PACT scale was used retrospectively to reconstruct psychosocial profiles of all patients who underwent a continuous-flow LVAD implantation for all indications at our institution between March 2008 and August 2012 (N = 230). Psychosocial elements including social support, psychological health, lifestyle factors, comprehension of the operation, and follow-up were evaluated. The primary outcome was overall survival, and the secondary outcomes were hospital readmission, pump thrombosis, hemolysis, gastrointestinal (GI) bleeding, and LVAD driveline infections. Results: The mean age of patients was 55.3 years, with 83% being male; 58% (N = 135) were bridge to transplant and 42% (N = 95) were destination therapy. Up to 1-year post-LVAD implant, there were no statistical differences among the 5 PACT candidate groups in terms of survival ( P = .79), hospital readmissions ( P = .55), suspected or confirmed pump thrombosis ( P = .31), hemolysis ( P = .43), GI bleeding ( P = .71), or driveline infections ( P = .06). Conclusions: In this single-center retrospective review, post hoc reconstruction of psychosocial profiles using the PACT scale and independent assessment of postimplant outcomes, including survival and adverse events, did not show any association. However, given the small number of patients in the low score PACT groups as well as limited duration of follow-up, further studies are required to elucidate the association.

Background: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N -acetyl-β- d -glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation–Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. Results: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300–815 mg), which induced a urine output of 8425 mL (interquartile range, 6341–10 528 mL) over the 72-hour intervention period. Levels of N -acetyl-β- d -glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P >0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (−8.7 ng/mg; interquartile range, −169 to 35 ng/mg; P <0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin ( P =0.21), N -acetyl-β- d -glucosaminidase ( P =0.46), or kidney injury molecule 1 ( P =0.22). Increases in neutrophil gelatinase-associated lipocalin, N -acetyl-β- d -glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69–0.91; P =0.001). Conclusions: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.