Aims:

To evaluate determinants and outcome of severe cardiovascular events (SCVE: ventricular tachycardia/fibrillation; sudden cardiac death) and impact of defibrillator (ICD)- therapy in Fabry disease (FD). 

Methods and results:

Between 2001 and 2019, 302 (n=124 males) FD-patients underwent comprehensive characterization including screening for SCVE and ICD-implantation with subsequent follow-up. N=30 (n=23 males) died during follow-up at mean age of 58±11 (range 27-80) years. Cardiac death (n_total=18; n_male=16) was predominant, followed by multi-organ failure/sepsis (n_total=5; n_male=4), stroke (n_total=4; n_male=3), cancer (n_total=; n_male=1), and committed suicide (n_male=1). Out of all patients, 27 (n_male=22) underwent ICD-implantation (48% primary-preventive) at age 54 (range 33-74) showing the following characteristics: NYHA-class: 2±0.8; LVEF: 58±10%; LVMI: 270±76 g/m2; E/A 0.95 (0.80-1.55); DT: 217±53 ms; sPAP 29±7 mmHg; GLS -11.7±3.8 %; NT-proBNP: 16171±58521 pg/ml. 

LV-thinning: IVSed [odds-ratio_{age/sex-adjusted} (95% CI)]: 0.641 (0.410-1.002), p=0.051; LVPW: 0.524 (0.294-0.934), p= 0.028); GLS-reduction ≥4% in any apical view [12.21 (0.96-154.51), p=0.053; sensitivity_{(95% CI)}: 0.667 (0.354-0.887); specificity_{(95% CI)}: 0.875 (0.467-0.993); positive-predictive-value (PPV)_{(95% CI)}: 0.889 (0.507-0.994); negative-predictive-value NPV_{(95% CI)}: 0.636 (0.316-0.876)]; the progression of LV remodeling [17.50 (1.60-191.89), p=0.019; sensitivity_{(95% CI)}: 0.714 (0.420-0.904); specificity_{(95% CI)}: 0.875 (0.467-0.993); PPV_{(95% CI)}: 0.909 (0.571-0.995); NPV_{(95% CI)}: 0.636 (0.316-0.876)] and the combined use (either LV remodeling or GLS worsening: 42.00 (3.20-551.57), p=0.004; sensitivity_{(95% CI)}: 0.857 (0.562-0.975); specificity_{(95% CI)}: 0.875 (0.467-0.993); PPV_{(95% CI)}: 0.923 (0.621-0.996); NPV_{(95% CI)}: 0.778 (0.412-0.96) are independent predictors of SCVE . 

Conclusions:

SCVE are the leading cause of death in FD. Worsening of LV-remodeling and/or GLS-reduction are independent risk factors for occurrence of SCVE and might thus be useful in disease-monitoring and evaluation of (primary)-prophylactic ICD-indication.