Author + information
- Received September 17, 2013
- Revision received November 6, 2013
- Accepted November 7, 2013
- Published online April 1, 2014.
- Selma F. Mohammed, MBBS∗,†,
- Sultan A. Mirzoyev‡,
- William D. Edwards, MD§,
- Ahmet Dogan, MD, PhD‖,
- Donna R. Grogan, MD¶,
- Shannon M. Dunlay, MD∗,
- Veronique L. Roger, MD∗,#,
- Morie A. Gertz, MD‖,
- Angela Dispenzieri, MD‖,
- Steven R. Zeldenrust, MD, PhD‖ and
- Margaret M. Redfield, MD∗∗ ()
- ∗Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- †Mayo Graduate School, Mayo Clinic, Rochester, Minnesota
- ‡Mayo Medical School, Mayo Clinic, Rochester, Minnesota
- §Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota
- ‖Division of Hematology, Mayo Clinic, Rochester, Minnesota
- ¶Clementia Pharmaceuticals, Montreal, Canada
- #Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
- ↵∗Reprint requests and correspondence:
Dr. Margaret M. Redfield, Mayo Clinic and Foundation, CV Research, Guggenheim 9, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
Objectives This study sought to determine the frequency of left ventricular amyloid in heart failure with preserved ejection fraction (HFpEF).
Background Left ventricular amyloid deposition can cause diastolic dysfunction and HFpEF.
Methods Autopsy of left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n = 109) and from control subjects (n = 131) were screened with sulfated Alcian blue and subsequent Congo red staining with microdissection for mass spectrometry–based proteomics to determine amyloid type. Fibrosis was assessed with quantitative whole-field digital microscopy.
Results The presence of wild-type transthyretin (wtTTR) amyloid was associated with age at death and male sex, but the age- and sex-adjusted prevalence of wtTTR amyloid was higher in HFpEF patients than in control subjects (odds ratio: 3.8, 95% confidence interval: 1.5 to 11.3; p = 0.03). Among HFpEF patients, moderate or severe interstitial wtTTR deposition, consistent with senile systemic amyloidosis as the primary etiology of HFpEF, was present in 5 (5%) patients (80% men), with mild interstitial and/or variable severity of intramural coronary vascular deposition in 13 (12%) patients. While, wtTTR deposition was often mild, adjusting for age and presence of HFpEF, wtTTR amyloid was associated with more fibrosis (p = 0.005) and lower age, sex, and body size–adjusted heart weight (p = 0.04).
Conclusions Given the age- and sex-independent association of HFpEF and wtTTR deposition and an emerging understanding of the pathophysiology of the amyloidoses, the current findings support further investigation of the role of wtTTR in the pathophysiology of HFpEF.
- heart failure with preserved ejection fraction
- mass spectrometry-based proteomics
The National Institutes of Health and the Mayo Clinic supported this study (grants #HL 72435, #HL 55502 and UL1 TR000135) and/or the investigators (grants #U01HL 84907 and #PO1HL 76611 to Dr. Redfield; T32-HL07111 to Dr. Mohammed). Dr. Mohammed is a heart failure clinical research network skills development fellow (U01HL 84907). A grant from FoldRx, a fully owned subsidiary of Pfizer, provided funds for technician support and mass spectrometry–based proteomics characterization. Dr. Grogan is an employee of FoldRx and has stock options. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Mohammed and Mr. Mirzoyev contributed equally to this work.
- Received September 17, 2013.
- Revision received November 6, 2013.
- Accepted November 7, 2013.
- American College of Cardiology Foundation