Left Atrioventricular Coupling for Predicting Incident Atrial Fibrillation in Cardiac Amyloidosis

ABSTRACT BACKGROUND: Amyloidosis is a heterogeneous group of infiltrative diseases characterized by protein misfolding and extracellular deposition of insoluble amyloid fibrils. When the heart is involved, cardiac amyloidosis (CA) occurs. There are multiple subtypes of CA, but two types are the most prevalent in clinical practice: immunoglobulin light-chain (AL) and transthyretin (ATTR) CA, which is in turn further subdivided into wild-type (ATTRwt) and hereditary (ATTRv). Previously thought as untreatable, nowadays CA are treated with disease-modifying drugs effectively ameliorating the prognosis. In this setting, high prevalence of atrial fibrillation (AF) emerged, especially in ATTRwt-CA. AF imposes a greater risk for heart failure hospitalisation and exacerbates the already preexisting elevated risk of intracardiac thrombi and systemic thromboembolism. Early detection of AF is therefore a key factor for proper initiation of anticoagulant therapy which in CA is independent from the CHA2DS2-VA score. AIMS: Previous studies in literature reported that impaired left atrioventricular coupling evaluated with 2D echocardiography is a predictive factor for the occurrence of new-onset AF, both in general population and patients with hypertrophic cardiomyopathy. Nevertheless, little is known in CA. Therefore, this study aims to investigate whether left atrioventricular coupling, using left atrial volumetric/mechanical coupling index (LACI), is predictive for AF onset also in patients with cardiac amyloidosis. MATERIALS AND METHODS: This was a single-centre, observational, retrospective study conducted in the outpatient clinic for Cardiac Amyloidosis at the University Hospital of Padua from the 1st of January 2018 until the 30th of June 2024. Consecutive patients with a diagnosis of CA, who were in sinus rhythm and had a complete echocardiographic examination and electrocardiogram available, were considered eligible for inclusion. Exclusion criteria were a previous diagnosis of AF of any type, including paroxysmal. Clinical, laboratory, ECG and echocardiographic data were collected from medical records. The primary outcome was the occurrence of de-novo AF. RESULTS: 93 patients with CA were included (median age 75 years, 70% male; 53% ATTR, 47% AL). During a median follow-up of 25 months, 19 patients (20%) developed AF. They more frequently had an ATTR form (73%), greater left ventricular mass (median value 272g/m2 ), more advanced diastolic dysfunction (median E/A 1.9, median a’ average 3.4cm/s), larger atrial volumes (median LAVi 48ml/m2 ), and markedly impaired atrial function (median LACI 13.4). In univariate analysis, age, ATTR etiology, LV mass index, LV ejection fraction, E/A ratio, a′ average, LAD, LAVi, LACI, and RAVi were associated with endpoint occurrence. On multivariate models LACI emerged as an independent predictor of incident AF. Patients with LACI ≥6 showed a significantly higher cumulative incidence of AF compared with those with lower LACI (12-month cumulative incidence 14.9% vs. 4.3%, respectively, p <0.001). CONCLUSION: Left atrioventricular coupling assessed through LACI is an independent predictor of new-onset AF in patients with CA. Its assessment may provide additional value in clinical decision-making to anticipate AF-related complications. Larger prospective studies are needed to confirm its prognostic role.