A new system that divides the extent of cardiac damage associated with Fabry disease into stages shows potential in predicting cardiovascular events in patients with the disease. Maria Chiara Meucci, MD, of Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, and colleagues, reported these findings in a manuscript published Monday online and in the Oct. 10 issue of the Journal of the American College of Cardiology. Study setup Anderson-Fabry disease, aka Fabry disease (FD), is a genetic neurological disorder in which the enzyme alpha-galactosidase-A is not sufficient to break down lipids. It involves multiple organs and is associated with high morbidity and mortality. Fabry cardiomyopathy is strong outcome predictor and typically manifests as left ventricular hypertrophy (LVH). Echocardiography is used to assess cardiac involvement with FD, and cardiac magnetic resonance (CMR) imaging has proven to be effective at characterizing tissue. Citing a lack of evidence-based risk stratification of patients with Fabry cardiomyopathy, the authors proposed classifying cardiac damage into distinct stages as shown by echocardiography. They did so using a large, contemporary cohort of Italian patients with FD. Patients from five referral centers in Italy were categorized into four stages of cardiac damage: stage 0 (no cardiac involvement), stage 1 (LVH, defined as left ventricle maximal wall thickness >12 mm), stage 2 (left atrium [LA] enlargement, defined as LA volume index >34 mL/m2), and stage 3 (ventricular impairment, defined as left ventricular ejection fraction <50% or E/e’ ≥ 15 or tricuspid annular plane systolic excursion [TAPSE] <17 mm). The study endpoint was the composite of all-cause death, hospitalization for heart failure, new-onset atrial fibrillation, major bradyarrhythmias or tachyarrhythmias, and ischemic stroke. Results The study included 314 patients. At baseline, their median age was 45 years (interquartile range: 31-55 years) and 56% were female. More than half of the patients (56%) were classified as stage 0, 13% as stage 1, 18% as stage 2 and 13% as stage 3. Patients with advanced cardiac damage were significantly older (stage 0, median age 33 years; stage 1, 50 years; stage 2, 55 years; stage 3, 60 years; p<0.001), and male patients constituted higher percentages of stages 1 (78%) and 3 (64%). Worse cardiac damage was associated with symptomatic heart failure (New York Heart Association functional class II-IV, sores renal function and hypertension. The 8-year rate of cardiovascular events progressively increased with each stage (stage 0 = 2%, stage 1 = 16%, stage 2 = 43%, stage 3 = 69%; log-rank p<0.001). Multivariate Cox regression analysis showed that cardiac damage stage was independently associated with risk of cardiovascular events (hazard ratio per 1-stage increase: 2.086; 95% confidence interval: 1.487-2.927; p<0.001). The authors added that cardiac staging showed a stronger and additive prognostic value than did degree of LVH. The authors noted several limitations to their study, including its retrospective and observational nature, as well as the system inferring that cardiac damage shown on echocardiography is related to FD but that it is possible that other comorbidities might have played a role in this damage. ‘Thoughtful and easily applicable’ In an accompanying editorial, Gere Sunder-Plassmann, MD, Senta Graf, MD, and Constantin Gatterer, MD, all of the University of Vienna, called the staging system described by Meucci et al. “thoughtful and easily applicable.” The editorialists did raise some issues with the study, including that none of the echocardiographic perimeters is specific to FD, and that echocardiography does not have the detection ability of CMR. While the echocardiography-based staging system is not perfect, the editorialists said it does represent a good start. They added that multimodality imaging, electrocardiogram, clinical assessments and laboratory results all need to be considered in managing patients with FD. “An ideal future model of Fabry cardiomyopathy could condense these data into pathophysiology-based stages that reflect the clinical events and symptoms of the patients,” the commenters concluded. “Staging classifications, using either echocardiography, as proposed in this study, or CMR, if available, may help to improve patient care in Fabry disease.” Sources: Meucci MC, Lillo R, Del Franco A, et al. Prognostic Implications of the Extent of Cardiac Damage in Patients With Fabry Disease. J Am Coll Cardiol. 2023;82:1524–1534. Sunder-Plassmann G, Graf S, Gatterer C. Staging of Fabry Cardiomyopathy by Echocardiography: Back to the Roots? J Am Coll Cardiol. 2023;82:1535–1537. Image Credit: Dzmitry – stock.adobe.com