Histopathologic Phenotypes Common in HFpEF

light micrograph of the heart with myocardial fibrosis
light micrograph of the heart with myocardial fibrosis
Endomyocardial biopsies from patients with HFpEF were found to commonly indicate myocardial fibrosis and hypertrophy.

Endomyocardial biopsies from patients with heart failure with preserved ejection fraction (HFpEF) were found to commonly indicate myocardial fibrosis and hypertrophy, according to a study published in the Journal of the American College of Cardiologists: Heart Failure.

A total of 108 patients with HFpEF who underwent right heart catheterization and endomyocardial biopsy between 2014 and 2018 were enrolled. Biopsies were examined histologically, and echocardiograms were conducted on study participants. Biopsy results were compared with those from control individuals (n=13) or patients with HF with reduced EF (HFrEF; n=20).

In this cohort, mean age was 66 years (interquartile range [IQR], 57-74 years) years, 61% were women, 57% were Black, median body mass index was 36.9 kg/m2 (IQR, 31.5-45.1 kg/m2), 93% of patients had hypertension, and 54% had comorbid diabetes. In addition, 99% of participants had a New York Heart Association functional class ³II, and 62% had been hospitalized for HF in the 12 months preceding the study.

Histological analysis of endomyocardial biopsies indicated that 93% of patients had myocardial fibrosis (66% mild or patchy; 17% moderate; and 10% severe). Myocyte hypertrophy was observed in 88% of samples (45% mild; 40% moderate; and 3% severe). Cardiac amyloidosis and borderline myocarditis were observed in 14% and 0.9% of patients, respectively).

Patients with nonamyloid HFpEF were more likely to exhibit fibrosis (6.3%; IQR, 3.1%-8.6%) compared with control participants (2.8%; IQR, 2.5%-3.6%; P =.003), but less likely to have fibrosis compared with patients with HFrEF (8.3%; IQR, 5.7%-11.6%; P =.03). CD68+ cells were more densely packed in endomyocardial tissues of patients with nonamyloid HFpEF (60.4 cells/mm2; IQR, 36.8-97.8 cells/mm2) compared with tissues of control individuals (32.1 cells/mm2; IQR, 22.3-59.2 cells/mm2; P =.02) or patients with HFrEF (26.5 cells/mm2; IQR, 2.7-65.3 cells/mm2; P =.003).

Moderate and severe hypertrophy was inversely related with troponin I levels ³0.04 ng/mL (odds ratio [OR], 0.24; 95% CI, 0.06-0.97; P =.045). Greater numbers of CD68+ cells were associated with lower glomerular filtration rate (b, 0.99; 95% CI, 0.99-1.00; P =.02) and increased age (b, 1.38; 95% CI, 1.02-1.87; P =.04).

HFpEF with cardiac amyloidosis was associated with age ³66 years (OR, 4.58; 95% CI, 1.17-17.96; P =.03), troponin I ³0.04 ng/ml (OR, 17.26; 95% CI, 3.72-80.10; P =.0003), the natural log of N-terminal-proB-type natriuretic peptide (OR, 1.93; 95% CI, 1.24-2.99; P =.003), left ventricle mass index per g/m2 (OR, 1.03; 95% CI, 1.01-1.06; P =.001), and decreased body mass index (OR, 0.85; 95% CI, 0.77-0.94; P =.002).

Study limitations include the fact that control tissues were obtained from unused donor hearts in which myocardial abnormalities were detected, which may have contributed to the donor’s death.

“Because of advances in noninvasive diagnostic testing and available new therapies, [cardiac amyloidosis] should be routinely considered and evaluated for as an etiology for HFpEF,” noted the study authors.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Hahn V S, Yanek L R, Vaishnav J, et al. Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis. JACC Heart Fail. 2020 Sep;8(9):712-724. doi:10.1016/j.jchf.2020.04.007