Myocardial Perfusion in Cardiac Amyloidosis

Q: What are the key findings of this study?

Cardiac amyloidosis was associated with severely reduced stress myocardial blood flow (1.04 ± 0.51 ml/min/g) compared to healthy volunteers (2.91 ± 0.73 ml/min/g).

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Cardiac amyloidosis (n=190). Intervention: Cardiac amyloidosis vs. Patients with 3-vessel coronary disease, unobstructed coronary arteries, or healthy volunteers. Primary outcome: Stress myocardial blood flow (MBF) (p=<0.001).

Q: What does this research mean for the field?

Cardiac amyloidosis is associated with severe inducible myocardial ischaemia, manifesting as severely reduced stress myocardial blood flow compared to healthy individuals and patients with three-vessel coronary artery disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Liza Chacko; Tushar Kotecha; Adam Ioannou; Niket Patel; Ana Martinez–Naharro; Yousuf Razvi; Rishi Patel; Paolo Massa; Lucia Venneri; James Brown; Aldostefano Porcari; Kristopher Knott; Charlotte Manisty; Daniel Knight; Tim Lockie; Roby Rakhit; Helen J. Lachmann; Ashutosh Wechelakar; Carol Whelan; Markella Ponticos; James Moon; Arantxa González; Janet A. Gilbertson; Mattia Riefolo; Ornella Leone; Hui Xue; Philip N. Hawkins; Peter Kellman; Julian D. Gillmore; Marianna Fontana

doi:10.1002/ejhf.3137

Key result

Cardiac amyloidosis is linked to ~64% lower stress myocardial blood flow versus healthy controls.

P<0.001
n=190

Why the study?

Preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage in systemic amyloidosis, but its presence and mechanisms required assessment.

Does cardiac amyloidosis reduce stress myocardial blood flow in affected patients compared to controls without the condition?

Study Design

Type

Cross-Sectional (n=190)

Multicenter

Yes

Structured PICO

Does cardiac amyloidosis reduce stress myocardial blood flow in affected patients compared to controls without the condition?

P

Population

190 participants across two centers, including 93 patients with cardiac amyloidosis and 97 controls, who underwent stress perfusion cardiovascular magnetic resonance to assess myocardial ischemia.

E

Exposure

Cardiac amyloidosis (exposure)

C

Comparator

Three-vessel coronary disease, unobstructed coronary arteries, and healthy volunteers

O

Outcome

Quantitative stress myocardial blood flow (MBF) using cardiovascular magnetic resonance mappingsurrogate

Main Result

Absolute Event Rate: 1.04% vs 2.91%

p-value: p=<0.001

This study demonstrates that cardiac amyloidosis causes severe microvascular ischemia and impaired myocardial perfusion independent of epicardial coronary disease.

Implication

Supports microvascular ischemia evaluation in cardiac amyloidosis; leaves open whether perfusion assessment guides therapy or prognosis.

Abstract

AIMS: Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. METHODS AND RESULTS: Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. CONCLUSION: Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

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Cite This Study

Chacko et al. (2024) conducted a cross-sectional in Cardiac amyloidosis (n=190). Cardiac amyloidosis vs. Patients with 3-vessel coronary disease, unobstructed coronary arteries, or healthy volunteers was evaluated on Stress myocardial blood flow (MBF) (p=<0.001). Cardiac amyloidosis was associated with severely reduced stress myocardial blood flow (1.04 ± 0.51 ml/min/g) compared to healthy volunteers (2.91 ± 0.73 ml/min/g).

synapsesocial.com/papers/6a207a43389e15e238f48ddf https://doi.org/10.1002/ejhf.3137