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Background Data regarding the phenotypic correlates and prognostic value of albumin in heart failure with preserved ejection fraction (HFpEF) are scarce. The goal of the current study is to determine phenotypic correlates (myocardial hypertrophy, myocardial fibrosis, detailed pulsatile hemodynamics, and skeletal muscle mass) and prognostic implications of serum albumin in HFpEF. Methods and Results We studied 118 adults with HFpEF. All‐cause death or heart‐failure–related hospitalization was ascertained over a median follow‐up of 57.6 months. We measured left ventricular mass, myocardial extracellular volume, and axial muscle areas using magnetic resonance imaging. Pulsatile arterial hemodynamics were assessed with a combination of arterial tonometry and phase‐contrast magnetic resonance imaging. Subjects with lower serum albumin exhibited a higher body mass index, and a greater proportion of black ethnicity and diabetes mellitus. A low serum albumin was associated with higher myocardial extracellular volume (52.3 versus 57.4 versus 39.3 mL in lowest to highest albumin tertile, respectively; P =0.0023) and greater N‐terminal pro B‐type natriuretic peptide levels, but not with a higher myocardial cellular volume (123 versus 114 versus 102 mL; P =0.13). Lower serum albumin was also associated with an increased forward wave amplitude and markedly increased pulsatile power in the aorta. Serum albumin was a strong predictor of death or heart failure hospitalization even after adjustment for N‐terminal pro B‐type natriuretic peptide levels and the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score (adjusted standardized hazard ratio=0.56; 95% CI=0.37–0.83; P <0.0001). Conclusions Serum albumin is associated with myocardial fibrosis, adverse pulsatile aortic hemodynamics, and prognosis in HFpEF. This readily available clinical biomarker can enhance risk stratification in HFpEF and identifies a subgroup with specific pathophysiological abnormalities.

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Background The impact of skeletal muscle size, quantified using simple noninvasive images routinely obtained during cardiac magnetic resonance imaging studies on mortality in the heart failure ( HF ) population is currently unknown. Methods and Results We prospectively enrolled 567 subjects without HF (n=364), with HF with reduced ejection fraction (n=111), or with HF with preserved ejection fraction (n=92), who underwent a cardiac magnetic resonance imaging. Skeletal muscle cross‐sectional area was assessed with manual tracing of major thoracic muscle groups on axial chest magnetic resonance images. Factor analysis was used to identify a latent factor underlying the shared variability in thoracic muscle cross‐sectional area. Cox regression was used to assess the relationship between these measurements and all‐cause mortality (median follow up, 36.4 months). A higher overall thoracic muscle area factor assessed with principal component analysis was independently associated with lower mortality (standardized hazard ratio, 0.51; P <0.0001). The thoracic muscle area factor was predictive of death in subjects with HF with preserved ejection fraction, HF with reduced ejection fraction, and those without HF . Among all muscle groups, the pectoralis major cross‐sectional area was the most representative of overall muscle area and was also the most robust predictor of death. A higher pectoralis major cross‐sectional area predicted a lower mortality (standardized hazard ratio, 0.49; P <0.0001), which persisted after adjustment for various confounders (standardized hazard ratio, 0.55; P =0.0017). Conclusions Axial muscle size, and in particular smaller size of the pectoralis major, is independently associated with higher risk of mortality in patients with and without HF . Further work should clarify the role of muscle wasting as a therapeutic target in patients with HF .

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