Tissue mapping by cardiac magnetic resonance imaging for the prognostication of cardiac amyloidosis: A systematic review and meta-analysis

Abstract

<h3>Background</h3><p>Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV).</p><h3>Methods</h3><p>Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis.</p><h3>Results</h3><p>A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m2 vs 127 ± 37 g/m2, <em>p</em> = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all <em>p</em> > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; <em>p</em> = 0.003; <em>I</em><em>2</em> = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], <em>p</em> < 0.0001; <em>I</em><em>2</em> <em>=</em> 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; <em>I</em><em>2</em> = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean).</p><h3>Conclusion</h3><p>Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis.</p>