Background

Progressive heart failure, conduction disorders and arrhythmias are the cardinal symptoms of amyloid transthyretin cardiomyopathy (ATTR-CM). Due to the limited overall prognosis, ICDs were rarely indicated in ATTR-CM. However, with the arrival of new targeted therapies, the role of ICD therapy for ATTR-CM should be reevaluated. Hence there is a need to identify patients who are at high risk for ventricular tachycardias (VT) who might possibly benefit from ICD therapy.

Methods

We prospectively investigated the presence of ventricular arrhythmias in a cohort of 63 ATTR-CM patients diagnosed at the German Heart Centre of Munich between 2020 and 2022 using 24 hours Holter-ECG. Ventricular arrhythmias included sustained (sVT) and non-sustained ventricular tachycardias (nsVT). In addition, we assessed clinical, laboratory and echocardiographic parameters.

Result

Overall, the prevalence of VTs in our cohort of unselected ATTR-CMP patients was high with 47.6 % (n= 30/63). The majority of patients presented with nsVT (43.5 %) while only 8.1% developed one or more sVT. 
Regarding baselines variables, patients with ventricular arrhythmias showed more severe left ventricular (LV) hypertrophy (intraventricular septum diameter [IVSd], 21 [20–22] vs. 19 [18-20] mm, p= 0.003), reduced LV ejection fraction (LVEF, 48 [43-57] vs. 54 [48-58] %, p= 0.025), larger left atrial volume (120 [96-135] ml vs. 97 [66-118], p= 0.021) and a trend towards smaller LV cavities (LV end-diastolic diameter [LVEDD], 42 [36 - 46] vs. 45 [41-50] mm, p= 0.057). Interestingly, there were no significant differences in prevalence of coronary artery disease or cardiac markers such as NTproBNP and Troponin T between patients with and without ventricular arrhythmias.
Furthermore, we evaluated the multivariable predictive performance for discriminating between patients with and without ventricular arrhythmias. Thereby, LVEF (OR= 0.865 [0.776-0.963], p= 0.008), LVEED (0.837 [0.708-0.991], p= 0.039), and LV mass indexed by BSA (1.028 [1.003-1.055], p= 0.031) remained independent predictors of occurrence of ventricular arrhythmias. The multivariable predictive model revealed a good discriminating performance, with an area under the receiver operating-characteristic (AUROC) 0.846 [0.711-0.937].

Conclusion

Prevalence of ventricular arrhythmia in patients with ATTR-CM is high. Patients presenting with ventricular arrhythmias show advanced stage of left ventricular disease, with LVEDD, LVEF and LV mass indexed by BSA being predictors of ventricular tachycardias in a multivariable predictive model. Further studies validating the predictive value of those variables are needed, including the assessment of nsVT and sVT in predicting sudden cardiac death, possibly allowing their use in a risk score for ventricular arrhythmias.