Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction

Selma F Mohammed, Sultan A Mirzoyev, William D Edwards, Ahmet Dogan, Donna R Grogan, Shannon M Dunlay, Veronique L Roger, Morie A Gertz, Angela Dispenzieri, Steven R Zeldenrust, Margaret M Redfield
JACC. Heart Failure 2014, 2 (2): 113-22

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.

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