Left ventricular hypertrophy, dilatation and ejection fractions predict ventricular tachycardia in amyloid transthyretin cardiomyopathy
Authors: Knoll K , Fuchs P , Weidmann I , Gross S , Altunkas F , Lennerz C , Kolb C , Kessler T , Schunkert H , Hengstenberg W , Trenkwalder T 
Published: May 2023

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Pfizer Global Medical Grant

Background

Amyloid transthyretin cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils. The disease is characterized by congestive heart failure, conduction abnormalities and arrhythmias. Due to the limited overall prognosis, ICDs were rarely indicated in ATTR-CM. However, with the development of new targeted therapies, the role of ICD therapy for ATTR-CM should be reevaluated. Hence, there is an urgent and unmet need to identify patients at high risk for ventricular tachycardias who might possibly benefit from ICD therapy.

Methods

Between 2020 and 2022, 120 patients were diagnosed with ATTR-CM in a tertiary referral center. Of those, 63 were prospectively evaluated for the presence of ventricular arrhythmias using 24 hours Holter-ECG. Ventricular arrhythmias were further characterized as sustained (sVT) and non-sustained ventricular tachycardias (nsVT).

Results

In our cohort of unselected ATTR-CMP patients the prevalence of ventricular tachycardias was high with 47.6 % (n= 30/63). Of those, the majority were non-sustained VTs (84%) and the minority sustained VT (16%). Patients with ventricular tachycardias showed significantly more severe left ventricular (LV) hypertrophy, reduced LV ejection fraction (LV-EF) and larger left atrial volumes as well as a trend towards smaller LV cavities (table 1). Interestingly, no significant differences in prevalence of coronary artery disease or cardiac markers such as NTproBNP and troponin were seen between patients with and without ventricular tachycardias (table 1).

Furthermore, we evaluated the multivariable predictive performance for discriminating between patients with and without ventricular tachycardias using two backward variable selection procedures (model 1 p-value based and model 2 Akaike information criterion (AIC) based). In the first model, 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, while in the second model sodium concentration (1.287 [0.929;1.783], p=0.129) and betablocker medication (5.078, [0.819;31.477], p=0.081) also were retained. Comparing the area under the Receiver Operating-Characteristic (AUROC) we observed no significant difference between both models (AUROC: 0.846 [0.711;0.937] vs. 0.870 [0.737;0.951], p=0.57, figure 1).

Conclusion

The prevalence of ventricular tachycardia in ATTR-CM is high. Patients with ventricular tachycardia show advanced stage of left ventricular disease, with LVEDD, LV-EF and LV mass indexed by BSA being predictors of ventricular tachycardias in two multivariable predictive models. 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 the use as a risk score for ventricular arrhythmias.