Author + information
- Received February 18, 2020
- Revision received April 3, 2020
- Accepted April 14, 2020
- Published online August 31, 2020.
- Virginia S. Hahn, MDa,
- Lisa R. Yanek, MPHb,
- Joban Vaishnav, MDa,
- Wendy Ying, MDa,
- Dhananjay Vaidya, MBBS, MPH, PhDb,
- Yi Zhen Joan Lee, MDa,
- Sarah J. Riley, MSN, CRNPa,
- Vinita Subramanya, MBBS, MPHc,
- Emily E. Brown, MGCa,
- C. Danielle Hopkins, BSa,
- Sandra Ononogbu, MBBSa,
- Kira Perzel Mandell, BSd,
- Marc K. Halushka, MD, PhDd,
- Charles Steenbergen Jr., MD, PhDd,
- Avi Z. Rosenberg, MD, PhDd,
- Ryan J. Tedford, MDe,
- Daniel P. Judge, MDe,
- Sanjiv J. Shah, MDf,
- Stuart D. Russell, MDg,
- David A. Kass, MDa and
- Kavita Sharma, MDa,∗ ()
- aDivision of Cardiology, The Johns Hopkins School of Medicine, Baltimore, Maryland
- bDivision of General Internal Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland
- cDepartment of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia
- dDepartment of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland
- eDivision of Cardiology, Medical University of South Carolina, Charleston, South Carolina
- fDivision of Cardiology, Northwestern University, Chicago, Illinois
- gDivision of Cardiology, Duke University, Durham, North Carolina
- ↵∗Address for correspondence:
Dr. Kavita Sharma, Advanced Heart Failure/Transplant Cardiology, The Johns Hopkins Hospital, 600 North Wolfe Street Carnegie 568B, Baltimore, Maryland 21287.
Objectives This study prospectively evaluated endomyocardial biopsies in patients with heart failure with preserved ejection fraction (HFpEF) to identify histopathologic phenotypes and their association with clinical characteristics.
Background Myocardial tissue analysis from a prospectively defined HFpEF cohort reflecting contemporary comorbidities is lacking.
Methods Patients with HFpEF (EF ≥50%) referred to the Johns Hopkins HFpEF Clinic between August 2014 and September 2018 were enrolled for right heart catheterization and endomyocardial biopsy. Clinical features, echocardiography, hemodynamics, and tissue histology were determined and compared with controls (unused donor hearts) and HF with reduced EF (HFrEF).
Results Of the 108 patients enrolled, median age was 66 years (25th to 75th percentile: 57 to 74 years), 61% were women, 57% were African American, 62% had a previous HF hospitalization, median systolic blood pressure was 141 mm Hg (25th to 75th percentile: 125 to 162 mm Hg), body mass index (BMI) was 37 kg/m2 (25th to 75th percentile: 32 to 45 kg/m2), and 97% were on a loop diuretic. Myocardial fibrosis and myocyte hypertrophy were often present (93% and 88%, respectively); however, mild in 71% with fibrosis and in 52% with hypertrophy. Monocyte infiltration (CD68+ cells/mm2) was greater in patients with HFpEF versus controls (60.4 cells/mm2 [25th to 75th percentile: 36.8 to 97.8] vs. 32.1 cells/mm2 [25th to 75th percentile: 22.3 to 59.2]; p = 0.02) and correlated with age and renal disease. Cardiac amyloidosis (CA) was diagnosed in 15 (14%) patients (HFpEF-CA: 7 patients with wild-type transthyretin amyloidosis [ATTR], 4 patients with hereditary ATTR, 3 patients with light-chain amyloidosis, and 1 patient with AA (secondary) amyloidosis), of which 7 cases were unsuspected. Patients with HFpEF-CA were older, with lower BMI, higher left ventricular mass index, and higher N-terminal pro−B-type natriuretic peptide and troponin I levels.
Conclusions In this large, prospective myocardial tissue analysis of HFpEF, myocardial fibrosis and hypertrophy were common, CD68+ inflammation was increased, and CA prevalence was 14%. Tissue analysis in HFpEF might improve precision therapies by identifying relevant myocardial mechanisms.
Dr. Hahn was supported by a National Institutes of Health (NIH) Training Grant (NIH 2T32HL007227-44). Dr. Sharma is supported by an American Heart Association Go Red for Women Network Grant (AHA #16SFRN28780016) and a Johns Hopkins University Clinician Scientist Award. Dr. Sharma is a consultant and advisory board member for Novartis and receives honoraria. Dr. Tedford has been a member of the Hemodynamic Core Lab for Merck and Actelion; has been a consultant for United Therapeutics and Arena Pharmaceuticals; has been a member of the Research Advisory Group for Abiomed; and has been a member of the Steering Committee for Medtronic. Dr. Judge has been a scientific advisor for 4DMT, ADRx Therapeutics, Blade Therapeutics, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received February 18, 2020.
- Revision received April 3, 2020.
- Accepted April 14, 2020.
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.