Heart Failure and Multimorbidity in Asia

Purpose of the Review Multimorbidity, the presence of two or more comorbidities, is common in patients with heart failure (HF) and worsens clinical outcomes. In Asia, multimorbidity has become the norm rather than the exception. Therefore, we evaluated the burden and unique patterns of comorbidities in Asian patients with HF. Recent Findings Asian patients with HF are almost a decade younger than Western Europe and North American patients. However, over two in three patients have multimorbidity. Comorbidities usually cluster due to the close and complex links between chronic medical conditions. Elucidating these links may guide public health policies to address risk factors. In Asia, barriers in treating comorbidities at the patient, healthcare system and national level hamper preventative efforts. Summary Asian patients with HF are younger yet have a higher burden of comorbidities than Western patients. A better understanding of the unique co-occurrence of medical conditions in Asia can improve the prevention and treatment of HF.</p

Patient-Reported Versus Physician-Assessed Health Status in Heart Failure With Reduced and Preserved Ejection Fraction From ASIAN-HF Registry

Background: We aimed to assess if discordance between patient-reported Kansas City Cardiomyopathy Questionnaire (KCCQ)-overall summary (os) score and physician-assessed New York Heart Association (NYHA) class is common among patients with heart failure (HF) with reduced or preserved ejection fraction, and determine its association with outcomes. Methods: A total of 4818 patients with HF were classified according to KCCQ-os score (range 0–100, dichotomized by median value 71.9 into high [good] versus low [bad]) and NYHA class (I/II [good] or III/IV [bad]) as concordant good (low NYHA class, high KCCQ-os score), concordant bad (high NYHA class, low KCCQ-os score), discordant worse NYHA class (high NYHA class, high KCCQ-os score), and discordant worse KCCQ-os score (low NYHA class, low-KCCQ-os score). The composite of HF hospitalization or death at 1 year was compared across groups. Results: There were 2070 (43.0%) concordant good, 1099 (22.8%) concordant bad, 331 (6.9%) discordant worse NYHA class, and 1318 (27.4%) discordant worse KCCQ-os score patients. Compared with concordant good, adverse outcomes were the highest in concordant bad (HR, 2.7 [95% CI, 2.2–3.5]) followed by discordant worse KCCQ-os score (HR, 1.8 [95% CI, 1.4–2.2]) and discordant worse NYHA class (HR, 1.5 [95% CI, 1.0–2.3]); with no modification by HF phenotype (preserved versus reduced ejection fraction, Pinteraction=0.52). At 6 months, 1403 (48%) experienced clinically significant improvement in KCCQ-os score (≥5 points increase over 6 months). Patients with improved KCCQ-os at 6 months (HR, 0.65 [95% CI, 0.47–0.92]) had better outcomes and the association was not modified by HF phenotype (Pinteraction=0.40). Conclusions: One-third of patients with HF had discordance between patient-reported and clinician-assessed health status, largely attributable to worse patient-reported outcomes. Such discordance, particularly in those with discordantly worse KCCQ, should alert physicians to an increased risk of HF hospitalization and death, and prompt further assessment for potential drivers of worse patient-reported outcomes relative to physicians’ assessment.</p

Multiomics Analysis Provides Novel Pathways Related to Progression of Heart Failure

Background: Despite major advances in pharmacological treatment for patients with heart failure, residual mortality remains high. This suggests that important pathways are not yet targeted by current heart failure therapies. Objectives: We sought integration of genetic, transcriptomic, and proteomic data in a large cohort of patients with heart failure to detect major pathways related to progression of heart failure leading to death. Methods: We used machine learning methodology based on stacked generalization framework and gradient boosting algorithms, using 54 clinical phenotypes, 403 circulating plasma proteins, 36,046 transcript expression levels in whole blood, and 6 million genomic markers to model all-cause mortality in 2,516 patients with heart failure from the BIOSTAT-CHF (Systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study. Results were validated in an independent cohort of 1,738 patients. Results: The mean age of the patients was 70 years (Q1-Q3: 61-78 years), 27% were female, median N-terminal pro–B-type natriuretic peptide was 4,275 ng/L (Q1-Q3: 2,360-8,486 ng/L), and 7% had heart failure with preserved ejection fraction. During a median follow-up of 21 months, 657 (26%) of patients died. The 4 major pathways with a significant association to all-cause mortality were: 1) the PI3K/Akt pathway; 2) the MAPK pathway; 3) the Ras signaling pathway; and 4) epidermal growth factor receptor tyrosine kinase inhibitor resistance. Results were validated in an independent cohort of 1,738 patients. Conclusions: A systems biology approach integrating genomic, transcriptomic, and proteomic data identified 4 major pathways related to mortality. These pathways are related to decreased activation of the cardioprotective ERBB2 receptor, which can be modified by neuregulin