Symptoms and signs in patients with heart failure: Association with 3-month hospitalisation and mortality

Objectives: To determine the association between symptoms and signs reported in primary care consultations following a new diagnosis of heart failure (HF), and 3-month hospitalisation and mortality. Design: Nested case-control study with density-based sampling. Setting: Clinical Practice Research Datalink, linked to hospitalisation and mortality (1998-2020). Participants: Database cohort of 86 882 patients with a new HF diagnosis. In two separate analyses for (1) first hospitalisation and (2) death, we compared the 3-month history of symptoms and signs in cases (patients with HF with the event), with their respective controls (patients with HF without the respective event, matched on diagnosis date (& plusmn;1 month) and follow-up time). Controls could be included more than once and later become a case. Main outcome measures: All-cause, HF and non-cardiovascular disease (non-CVD) hospitalisation and mortality. Results: During a median follow-up of 3.22 years (IQR: 0.59-8.18), 56 677 (65%) experienced first hospitalisation and 48 146 (55%) died. These cases were matched to 356 714 and 316 810 HF controls, respectively. For HF hospitalisation, the strongest adjusted associations were for symptoms and signs of fluid overload: pulmonary oedema (adjusted OR 3.08; 95% CI 2.52, 3.64), shortness of breath (2.94; 2.77, 3.11) and peripheral oedema (2.16; 2.00, 2.32). Generic symptoms also showed significant associations: depression (1.50; 1.18, 1.82), anxiety (1.35; 1.06, 1.64) and pain (1.19; 1.10, 1.28). Non-CVD hospitalisation had the strongest associations with chest pain (2.93; 2.77, 3.09), fatigue (1.87; 1.73, 2.01), general pain (1.87; 1.81, 1.93) and depression (1.59; 1.44, 1.74). Conclusions: In the primary care HF population, routinely recorded cardiac and non-specific symptoms showed differential risk associations with hospitalisation and mortality. & copy; Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ

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