Heart failure in Fabry disease revisited: application of current heart failure guidelines and recommendations

Abstract

Aims Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain. Methods and results We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow‐up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58 ± 11 years, 62% male). HF with preserved ejection fraction (HF‐pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e′ > 9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) <16% (sensitivity 54% and specificity 88%). Log N‐terminal pro‐brain natriuretic peptide correlated significantly with LVMi (r = 0.60), E/e′ (r = 0.54), and GLS (r = 0.52) (all Ps < 0.001) but not with left ventricular ejection fraction (r = −0.034, P = 0.72). During follow‐up (mean 1208 ± 444 days), patients diagnosed with HF had a higher rate of all‐cause mortality and worsening HF (33% vs. 1.5%, P < 0.001). Abnormal LVMi, E/e′ > 9, and GLS < 16% were all associated with higher all‐cause mortality and worsening HF. Conclusions This study found a high prevalence of symptomatic HF in FD patients. HF‐pEF was the dominant phenotype. LVMi, E/e′, and GLS yielded the highest diagnostic utility for HF diagnosis and were significantly correlated with natriuretic peptides levels. Echocardiographic criteria proposed by current ESC HF guidelines apply to Fabry patients and predict cardiovascular events. At follow‐up, Fabry patients with HF diagnosis had high event rates and significantly worse prognosis than patients without HF.

Experimental evidence and clinical implications of Warburg effect in the skeletal muscle of Fabry disease

“… 2 , 3 , 4 , 5 , 6 FD is a systemic disease with a wide spectrum of heterogeneously progressive clinical phenotypes; this spectrum ranges from the “classic” severe phenotype in males to a seemingly asymptomatic disease observed in females, with a variety of clinical presentations in between. 7 , 8 , 9 , 10 , 11 , 12 Pain is one of the earliest clinical symptoms of FD, also reported by children and young adults, 13 , 14 and life-impacting pain may still be present despite long-term enzyme replacement therapy (ERT), thereby requiring the use of adjunctive medications. Exercise intolerance even to mild physical activity has been reported in FD patients, 7 , 15 , 16 occurring also in the absence of a marked left ventricle hypertrophy, making this sign independent of cardiac impairment, such as diastolic dysfunction.…”

Assessing small fiber neuropathy and subtle cardiac involvement in Fabry disease

“…Assessment of GLS and T1 mapping /CMR were pivotal at presented cases. GLS (obtained by speckel-tracking echo or CMR) has been shown to add diagnostic value in heart disease associated with FD [32][33]. Although nonspecific, reduced GLS can present including reduced longitudinal strain in the basal inferolateral segment, and it has been described as useful to detect subclinical cardiomyopathy [34].…”

Cerebrovascular Phenotype in Fabry Disease Patients Assessed by Ultrasound

“…The evaluation of FD patients was a part of a more extensive systematic diagnostic program of the National Referral Center for FD, which also included echocardiography, and its detailed procedures were reported previously 20 . Sixty‐five FD adult patients (38 females, mean age 47.24, range 20–73; 27 males, mean age 47.56, range 20–70) with genetically confirmed pathogenic GLA variant were consecutively included in the study during their regular follow‐up to assess the presence and severity of neurological manifestations of the disease.…”