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Left ventricular amyloid deposition in patients with heart failure and preserved
ejection fraction
#MMPMID24720917
Mohammed SF
; Mirzoyev SA
; Edwards WD
; Dogan A
; Grogan DR
; Dunlay SM
; Roger VL
; Gertz MA
; Dispenzieri A
; Zeldenrust SR
; Redfield MM
JACC Heart Fail
2014[Apr]; 2
(2
): 113-22
PMID24720917
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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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