Clinical and genetic predictors of major cardiac events in patients with Anderson–Fabry Disease

Abstract

AFD is associated with a high burden of cardiac morbidity and mortality. Adverse cardiac outcomes are associated with age, global disease severity and advanced cardiac disease but not the presence of cardiac genetic variants.

A focus on the prognosis and management of ischemic heart disease in patients without evidence of obstructive coronary artery disease

“…Recently, an observational study by Patel et al conducted in AFD patients showed the following incidence rates: 1.62/100 person-years for HF, 1/100 person-years for atrial fibrillation and 0.52/100 person-years for overall death [73].…”

Adult patients with Fabry disease: what does the cardiologist need to know?: Table 1

“…In the study by Patel and colleagues, QRS duration was a significant independent predictor of the primary endpoint; a value ≥120 ms had a positive predictive value of 88% with a negative predictive value of 41% for the occurrence of the composite primary endpoint 5. While QRS duration is often increased in parallel with cardiac hypertrophy, indexed ventricular mass is an independent predictor of atrial fibrillation and the only predictor of cardiac death 5…”

“…The objective of the study was to compare the prognosis of FD in patients ≥16 years with the classic form (multiorgan involvement, n=149) versus patients with mutations ((p.Asn215Ser), (p.Met296Val), (p.Gln279Glu), (p.Arg301Gln), (p.Met296Ile), (p.Ile91Thr), (p.Phe113Leu), (p.Arg112His), (p.Gly328Arg) and the ‘Chinese’ IVS4+919A>G intronic mutation) previously associated with a cardiac prominent/exclusive phenotype (‘cardiac variants’) (n=58) 5. The primary aims were to determine the incidence of a composite (the primary endpoint) of new-onset atrial fibrillation, severe heart failure (New York Heart Association class ≥3), antibradycardia device insertion and cardiac death, and to identify clinical and genetic predictors of those events.…”

“…However, in the study by Patel and colleagues, patients with cardiac variant mutations and patients with classical FD shared a similar malignant prognosis, at least when focusing on cardiac morbidity and mortality (cardiac composite endpoint ∼16% vs ∼10%, respectively) as no data were available for renal or cerebrovascular outcome 5. Interestingly, patients with cardiac variants occasionally showed normal LV wall thickness and/or mass, demonstrating that the current definition of such variants might be too simplistic and warrants better phenotypic characterisation.…”

“…While the prognostic importance of genotype needs further studies, disease duration (reflected by increasing age) and overall disease severity (reflected in an increased Mainz Severity Score Index) are the main variables in determining adverse events in patients with FD 5. In a recent report on a small group of 25 male patients with FD followed 10 years after initiation of ERT, end-stage renal disease, another indicator of the overall severity of the disease, was the strongest indicator of cardiovascular disease progression in FD: major cardiac events (including sudden death, arrhythmia and pacing device insertion) occurred in 100% of patients with end-stage renal disease versus only 26% in the remaining patients (p<0.0001) 8…”