Health-Related Quality of Life Across the Spectrum of Pulmonary Hypertension.

BACKGROUND: Health-related quality of life (HRQOL) is frequently impaired in pulmonary arterial hypertension. However, little is known about HRQOL in other forms of pulmonary hypertension (PH). RESEARCH QUESTION: Does HRQOL vary across groups of the World Symposium on Pulmonary Hypertension (WSPH) classification system? STUDY DESIGN AND METHODS: This cross-sectional study included patients with PH from the Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort study. HRQOL was assessed by using emPHasis-10 (e-10), the 36-item Medical Outcomes Study Short Form survey (physical component score [PCS] and mental component score), and the Minnesota Living with Heart Failure Questionnaire. Pearson correlations between HRQOL and demographic, physiologic, and imaging characteristics within each WSPH group were tested. Multivariable linear regressions compared HRQOL across WSPH groups, adjusting for demographic characteristics, disease prevalence, functional class, and hemodynamics. Cox proportional hazards models were used to assess associations between HRQOL and survival across WSPH groups. RESULTS: Among 691 patients with PH, HRQOL correlated with functional class and 6-min walk distance but not hemodynamics. HRQOL was severely depressed across WSPH groups for all measures except the 36-item Medical Outcomes Study Short Form survey mental component score. Compared with Group 1 participants, Group 2 participants had significantly worse HRQOL (e-10 score, 29 vs 24 [P = .001]; PCS, 32.9 ± 8 vs 38.4 ± 10 [P < .0001]; and Minnesota Living with Heart Failure Questionnaire score, 50 vs 38 [P = .003]). Group 3 participants similarly had a worse e-10 score (31 vs 24; P < .0001) and PCS (33.3 ± 9 vs 38.4 ± 10; P < .0001) compared with Group 1 participants, which persisted in multivariable models (P < .05). HRQOL was associated in adjusted models with survival across Groups 1, 2, and 3. INTERPRETATION: HRQOL was depressed in PH and particularly in Groups 2 and 3 despite less severe hemodynamics. HRQOL is associated with functional capacity, but the severity of hemodynamic disease poorly estimates the impact of PH on patients' lives. Further studies are needed to better identify predictors and treatments to improve HRQOL across the spectrum of PH.

Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease.

BACKGROUND: PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification. OBJECTIVES: The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort. METHODS: Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death. RESULTS: A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH. CONCLUSIONS: PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887).

Comprehensive Diagnostic Evaluation of Cardiovascular Physiology in Patients With Pulmonary Vascular Disease: Insights From the PVDOMICS Program.

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.

A new class of drugs for systolic heart failure: The PARADIGM-HF study.

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.

Biomarkers in pulmonary arterial hypertension.

Pulmonary hypertension prevalence continues to rise and remains a clinical dilemma with regards to patient recognition and management. Despite advances in our understanding of the pathophysiology and pathogenesis behind pulmonary hypertension (PH), this heterogeneous cohort continues to demonstrate significant morbidity and mortality. Biomarkers serve as a dynamic, noninvasive tool in a physician's clinical armamentarium. Their role is to impact clinical decision-making and to facilitate patient education with respect to diagnosis, prognosis, and therapeutic intervention. This review will elucidate the relationship between PH and serum biomarkers related to inflammation, myocardial dysfunction or stress, and endothelial dysfunction. Over the last two decades, the utilization and incorporation of biomarkers into the evaluation and management of pulmonary hypertension has exploded. Consequently, current guidelines and consensus documents have adopted their use. The additive roles of both established and innovative biomarkers in individuals with pulmonary arterial hypertension (PAH) will be discussed.

Management of implantable assisted circulation devices: emergency issues.

As the prevalence of systolic heart failure increases, the population of patients in need of advanced therapies becomes larger. As the number of transplants performed each year plateaus, the prevalence of community-dwelling patients with ventricular assist devices (VADs) increases. A broad range of physicians, including emergency physicians, general cardiologists, and generalists, will be exposed to these patients, and must be informed on the disease processes and complications specific to these devices. With an understanding of up-front evaluation and management, these patients may be triaged and stabilized, and will benefit before referral for definitive care by a VAD specialist.

Aldosterone-receptor antagonists in heart failure: insights after EMPHASIS-HF.

The recent publication of the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) has affirmed the important role of aldosterone-receptor antagonism across the spectrum of systolic heart failure. Previously restricted as therapy in patients with severe symptomatic or postinfarction heart failure, it now is being considered in less-sick patients. The precise mechanisms of benefit remain to be elucidated, in part due to the observed discrepancy between improved outcomes and the lack of reverse cardiac remodeling with aldosterone-receptor antagonists. With the probable increased use of spironolactone and eplerenone, there are concerns for increased complications, especially hyperkalemia. This risk must be balanced against the potential benefit for reduced mortality and morbidity in addition to effects of ß-blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and cardiac resynchronization therapy.