Left Ventricular Amyloid Deposition in Patients With Heart Failure and Preserved Ejection Fraction

Mohammed, Selma F.; Mirzoyev, Sultan A.; Edwards, William D.; Doğan, Ahmet; Grogan, Donna R.; Dunlay, Shannon M.; Roger, Véronique L.; Gertz, Morie A.; Dispenzieri, Angela; Zeldenrust, Steven R.; Redfield, Margaret M.

doi:10.1016/j.jchf.2013.11.004

Cited by 335 publications

(251 citation statements)

References 38 publications

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“…Incidental deposits of amyloid have been reported in 1% of surgical septal myectomy specimens from patients with hypertrophic cardiomyopathy. 32,33 Mohammed et al 34 reported 17% prevalence of ATTR amyloid in patients with heart failure with preserved ejection fraction on autopsy with a substantial (80%) male predominance. In contrast to this series and the wider clinical impression, half of the patients with amyloid in our cohort were women; this was also a finding in a recent cohort of patients with heart failure with preserved ejection fraction who were studied with DPD scintigraphy, 35 suggesting that the incidence may be underestimated in women generally, possibly because of a lower frequency of extreme hypertrophy that serves as the main red flag.…”

Section: Attr Amyloid and Heart Failurementioning

confidence: 99%

Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis

Treibel

Fontana

Gilbertson

et al. 2016

Circ: Cardiovascular Imaging

225

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Severe degenerative calcific aortic stenosis (cAS) is common, affecting 3% of individuals aged >75 years and leads to heart failure and death unless the valve is replaced.1,2 Its coexistence with cardiac amyloidosis has been reported, but this has not been studied systematically and the prognostic significance is unknown.3 Cardiac amyloidosis is a progressive infiltrative cardiomyopathy in which deposits of amyloid, almost always of either immunoglobulin light-chain (AL) or transthyretin amyloidosis (ATTR) type, 4-6 accumulate in the ventricular myocardium; ATTR amyloid is usually wildtype (wtATTR) and acquired, but it may also be hereditary and associated with mutant forms of transthyretin. Wild-type cardiac ATTR amyloid has a male preponderance and was formerly known as senile amyloid reflecting its first appearance beyond 60 to 70 years of age and prevalence at autopsy of up to 25% among octogenarians. 7,8 Its natural history and the prevalence of clinically significant ATTR amyloid deposition in the heart are unknown. In a recent small cohort of patients with AS who underwent transcatheter aortic valve Background-Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance. Methods and Results-A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and 99m TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69-85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5-35.8]; P=0.001). Conclusions-Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome. (Circ Cardiovasc Imaging. 2016;9:e005066.

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Section: Attr Amyloid and Heart Failurementioning

confidence: 99%

Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis

Treibel

Fontana

Gilbertson

et al. 2016

Circ: Cardiovascular Imaging

225

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“…It is reported that 13% of HFpEF cases were diagnosed as ATTRwt 6. Furthermore, several post‐mortem studies found cardiac amyloid deposition in up to 25% of individuals >80 years of age 7, 8. Therefore, it is important to suspect and differentiate cardiac amyloidosis from HFpEF of other aetiologies for the selection of appropriate therapy and prediction of prognosis.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis

et al. 2017

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AimThe aim of this study was to evaluate the diagnostic utility of high‐sensitivity cardiac troponin T (hs‐cTnT) levels in discriminating cardiac amyloidosis from patients with cardiac hypertrophy caused by aetiologies other than cardiac amyloidosis.Methods and resultsSerum hs‐cTnT levels were measured in 96 patients with cardiac amyloidosis (light chain: 23, wild‐type transthyretin amyloidosis: 40, and mutated transthyretin amyloidosis: 33), and 91 patients with other causes of cardiac hypertrophy who were confirmed to have no cardiac amyloidosis by endomyocardial biopsy (control group). The diagnostic utility and cut‐off value of hs‐cTnT were evaluated by receiver operating characteristic analysis. The median hs‐cTnT levels were higher in cardiac amyloidosis than the control group [0.048 (0.029–0.073) vs. 0.016 (0.010–0.031) ng/mL; P < 0.001]. High levels of hs‐cTnT were suggestive of cardiac amyloidosis (cut‐off value: 0.0312 ng/mL, sensitivity: 0.74, specificity: 0.76, area under the curve: 0.788; 95% confidence interval: 0.723–0.854, P < 0.001), compared with brain natriuretic peptide and E/e′ ratio. The hs‐cTnT levels were also useful in differentiating each type of amyloidosis from the control group. Multivariate analysis identified log hs‐cTnT as an independent diagnostic factor for cardiac amyloidosis (odds ratio: 2.22; 95% confidence interval: 1.30–3.80; P = 0.004).ConclusionsHigh serum levels of hs‐cTnT are highly suggestive of cardiac amyloidosis, allowing its differentiation from cardiac hypertrophy of other aetiologies. Further refined diagnostic approaches that include imaging modalities and histopathological examination are needed for these patients to avoid underdiagnosis of cardiac amyloidosis.

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“…This manifestation of diastolic dysfunction is associated with increased morbidity and mortality and can be attributed to a variety of pathogeneses, including diabetes mellitus, hypertension, infiltrative processes, and obesity. [1][2][3][4][5] Unlike in systolic heart failure, where LV ejection fraction readily stratifies disease severity, accurate diagnosis and grading of heart failure with preserved ejection fraction (HFpEF) can be a challenging. Without an equivalent, single, noninvasive diagnostic tool in HFpEF, we must instead rely on a myriad of measures to establish diagnosis and severity.…”

mentioning

confidence: 99%