1Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I Würzburg, Deutschland
Aim: Quality of Life (QoL) in patients with Fabry Disease (FD) is known to be substantially reduced in comparison to the general population. It is currently unclear whether this primary is a direct effect of the Fabry neuropathy or secondary to extra-neurological organ involvment in Fabary disease. Cardiac involvement has been revealed the major prognostic factor in several recent studies, however its impact on QoL is not well investigated. We investigated the correlation between the cardiomyopathy stage as measured by echocardiography and QoL in patients with FD.
Methods: This single center study included 122 patients (mean age 39.9 years (IQR 16-72 years), 43.4% male) with a confirmed genetic diagnosis of FD. Patients‘ self-reported outcomes were obtained using the Short Form (36) Health Survey (SF-36), analyzing eight items of QoL: physical functioning, role limitations due to physical health and emotional problems, energy/fatigue, emotional well being, social functioning, pain and general health. In total, 407 echocardiographic examinations and their corresponding QoL between June 2002 and October 2022 were analysed. Possible correlation was invastigated and reported using Spearman correlation coefficient.
Results: In total, 64.8% (79/122) of FD patients presented with a classic mutation. Fabry specific treatment was initiated in 67.2% (82/122, 56.6% enzyme replacement, 10.7% chaperone therapy) at baseline visit. All patients presented at least with one organ manifestation (54.9% cardiomyopathy, 53.3% nephropathy and 62.3% neuropathy). Mean echocardiographic parameters were within normal ranges (LVEF 61.8±7.3%, LVMi 75.9±37.4g/m2). Regarding QoL, the worst rated item at baseline was energy/fatigue (49.2±18.7%).
All eight QoL dimensions of QoL showed negative and positive correlations with certain echocardiographic parameters. Physical functioning was specifically strong correlated with echocardiographic parameters, including left heart morphology (IVSd (r= -0.401 p<0.001), LVPWd (r= -0.309 p<0.001), LVMi (r= -0.261 p<0.001), LAD (r= -0.402 p<0.001), LAA (r= -0.358 p< 0.001)), diastolic function (E/e‘ septal (r= -0.378 p<0.001)) and systolic function (TAPSE (r= 0.239 p<0.001), sPAP (r= -0.168 p=0.005)).
IVSd and E/e‘ septal were negatively correlated to all eight items of QoL, e.g. pain-IVSd r=-0.171 p<0.001, pain-E/e‘ septal r= -0.155 p=0.008; emotional well being- IVSd r=-0.174 p<0.001, emotional well being-E/e‘ septal r=-0.245 p<0.001).
Discussion: QoL in patients with FD shows a strong correlation to Fabry cardiomyopathy stage as measured by various echocardiographic parameters. Poorer QoL was observed in patients with increased wall thickness (IVSd, LVPWd, LVMi), enlarged left atrial dimensions (LAD, LAA) as well as deteriorated diastolic (E/e‘ septal) and systolic (TAPSE, sPAP) function. We therefore assume that cardiac involvement itself has a negative contributory impact on QoL. Patients with FD should be encouraged to focus actively on cardiovascular prevention, including early initiation and adherence to specific and non-specific treatment, treatment of comorbidities, and potential beneficial lifestyle modifications such as regular physical exercise and reducing psychosocial stress.