Prevalence and clinical implications of conduction system disease in patients with cardiac transthyretin amyloidosis

Background
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cardiomyopathy in which conduction system disease is common. Due to increased awareness more patients are diagnosed at an early disease stage and targeted therapies have the potential to halt progression of the disease manifestations including arrhythmic complications. The aim of our study was to define the prevalence and clinical implications of atrioventricular (AV) block, interventricular and intraventricular conduction delay in a contemporary cohort of patients with ATTR-CA.

Methods
This is a single-center retrospective cohort study of patients, who presented at a quaternary referral center and underwent 12-lead surface electrocardiogram (ECG) at the time of ATTR-CA diagnosis. Patients requiring pacing at the time of the ECG recordings were excluded from analysis of verntricular conduction. CA severity was defined using the UK National Amyloidosis Center (NAC) Staging System.

Results
During a 10 month-period, 64 consecutive patients were diagnosed with ATTR-CA at our center. At the time of ATTR-CA diagnosis, 13 (20%) patients had pacemakers in situ for high-grade AV block. Ten patients were excluded from the analysis of ventricular conduction due to paced ECG at initial presentation. The mean age of the overall study cohort was 82±5 years and the study population was predominantly male (86%). The NAC-Stage was 1 in 38 patients (59%), 2 in 14 patients (22%) and 3 in 12 patients (19%) respectively.  

On initial ECG 31 (48%) patients were in sinus rhythm (SR), whereas 23 (36%) were in atrial fibrillation (AF). In the group of SR (n=31), the average heart rate was 67±11 bpm. First-degree AV block was present in 19 (33%) and ≥2. degree AV block present in 2 (3%).

In the subgroup without paced ECG (n=54), a wide QRS complex (QRS > 120 ms) was observed in 13 (24%), of whom 4 (7%) had left bundle branch block, 3 (5%) had right bundle branch block and 6 (9%) had interventricular conduction delay. Left anterior fascicular block was present in 8 (15%) patients and left posterior fascicular block was present in 2 (4%), while bifascicular block was observed in 5 (10%) patients, respectively.

The most common conduction abnormality on the baseline ECG was a first-degree AV block, which was present in 19 (33%), followed by a wide QRS complex (QRS>120ms) present in 13 (24%). AV conduction abnormality of any degree was not associated with NAC disease stage (p=0,16), NYHA class (p=0,68), age (p=0,96), coronary artery disease (p=0,66), septal thickness (p=0,91), LV hypertrophy (p=0,19), LVEF (p=0,50) or beta blocker intake (p=0,09) by univariate analysis.

QRS > 120 ms was associated with LV hypertrophy (p=0,02) and coronary artery disease (p=0,03) but not with NAC stage (p=0,76), NYHA class (p=0,92), age (p=0,43), septal thickness (p=0,08), LVEF (p=0,82) or beta blocker intake (P=0,28).

Conclusions
The prevalence of conduction system disease is high in patients with ATTR-CA, suggesting that close monitoring for the development of advanced AV block and dyssynchrony is prudent. However, the prevalance of conduction abnormalities does not correlate with disease stage in a contemporary patient sample. The trajectory of conduction system disease under current targeted therapies, along with its impact on clinical outcomes, remains an area of active interest and warrants further investigation in future studies.