Is acute heart failure a distinctive disorder? An analysis from BIOSTAT‐CHF

Aims This retrospective analysis sought to identify markers that might distinguish between acute heart failure (HF) and worsening HF in chronic outpatients. Methods and results The BIOSTAT‐CHF index cohort included 2516 patients with new or worsening HF symptoms: 1694 enrolled as inpatients (acute HF) and 822 as outpatients (worsening HF in chronic outpatients). A validation cohort included 935 inpatients and 803 outpatients. Multivariable models were developed in the index cohort using clinical characteristics, routine laboratory values, and proteomics data to examine which factors predict adverse outcomes in both conditions and to determine which factors differ between acute HF and worsening HF in chronic outpatients, validated in the validation cohort. Patients with acute HF had substantially higher morbidity and mortality (6‐month mortality was 12.3% for acute HF and 4.7% for worsening HF in chronic outpatients). Multivariable models predicting 180‐day mortality and 180‐day HF readmission differed substantially between acute HF and worsening HF in chronic outpatients. Carbohydrate antigen 125 was the strongest single biomarker to distinguish acute HF from worsening HF in chronic outpatients, but only yielded a C‐index of 0.71. A model including multiple biomarkers and clinical variables achieved a high degree of discrimination with a C‐index of 0.913 in the index cohort and 0.901 in the validation cohort. Conclusions This study identifies different characteristics and predictors of outcome in acute HF patients as compared to outpatients with chronic HF developing worsening HF. The markers identified may be useful in better diagnosing acute HF and may become targets for treatment development. Differential protein expression in inpatients relative to outpatients. Presented is a volcano plot of differential protein expression showing the fold change (FC), i.e. the ratio of average expression in inpatients to average expression in outpatients, vs. the corresponding t‐test P‐value per protein and on logarithmic scales. Higher values on the y‐axis indicate stronger statistical significance, values >0 on the x‐axis indicate up‐regulation in inpatients, and values