Dottorato in ARTERIAL HYPERTENSION AND VASCULAR BIOLOGY

Titolo della tesi: ELECTRICAL AND ANATOMICAL ATRIAL REMODELING IN PATIENTS WITH CEREBRAL ISCHEMIA OF UNKNOWN ETIOLOGY

Introduction: Stroke is one of the leading causes of morbidity and mortality. In a significant percentage of strokes, the exact etiology remains undetermined. Early left atrial (LA) anatomical and electrical remodeling, a substrate for atrial fibrillation (AF), may play a role in identification of the etiology of crytogenic stroke (CS). We aimed to assess whether LA mechanical and electrical early subclinical changes predicts AF occurrence in a population of patients with cerebral ischemia of unknown etiology who received an implantable loop recorder (ILR) for long -term ECG monitoring. Methods: Consecutive patients with CS or transient ischemic attack (TIA) monitored with an ILR were enrolled. At baseline, conventional ECG, echocardiogram and P wave signal-averaged electrocardiography (P-SAECG) were performed. The echocardiograms were evaluated for standard parameters and LA strain (reservoir strain (ƐR), contractile strain (ƐCt), and conduit atrial strain (ƐCd)). All patients were remotely monitored and AF occurrence was evaluated during the follow up. Results: Fifty consecutive patients receiving ILRs for CS or TIA were included. During a follow up of 15  9 months, AF was detected in 18 patients (36%). The median time to AF detection was 5 months (range 1.5-10). AF patients were older than non-AF patients (72  7 vs 61 13 years; p= 0.002); there were no other significant differences in demographic characteristics and clinical cardiovascular risk factors. Although LA dimensions were similar in the two group, all atrial strain indices were lower in the AF compared to non-AF group (ƐR 22.8  6.2 vs 32.9  12.1, p 0.002; ƐCd 9.0  2.5 vs 14.9  8.4, p 0.006; ƐCt 13.8  7.0 vs 18.3  7.1, p 0.04). P wave duration at ECG was similar in the two groups, while filtered P wave duration (FPD) was significantly longer in the AF group (129  9 msec vs 119  12 msec; p=0.01) and the root mean square voltage of the last 30 ms of the P wave (RMS 30) was significantly lower in the AF group (2.76, IQR 2.17-3.68 vs 3.35, IQR 2.95-3.67; p=0.04). Based on the area under the ROC curve (AUC), all atrial strain parameters, FPD and RMS 30 correctly classified the endpoint of AF occurrence, with ƐR emerging as the best discriminator (AUC: 0.82; 95%CI 0.68-0.95; p< 0.001). In ROC analysis curves, ƐR < 24.6%, ƐCd < 11.05%, ƐCt < 13.55%, FPD  125 msec, RMS 30 < 3.24 V displayed the best combined sensitivity and specificity for AF occurrence. In multivariate analysis after correction for age and CHA2DS2VASC score, ƐR < 24.6%, ƐCd < 11.05%, ƐCt < 13.55%, FPD  125 msec and RMS30 < 3.24 V were significantly associated with higher risk of AF occurrence. Concordant impairment of all strain or SAECG parameters was associated with a significantly increased risk of developing AF (HR: 5.45; 95% CI: 1.84–16.13; P=0.002 and HR: 3.27; 95% CI: 1.11–9.64; P=0.03, respectively). In Kaplan–Meier analysis, patients with all strain measurements or both SAECG P wave parameters impaired had higher cumulative incidence of AF detection, with marked stepwise increase of AF occurrence (p <0.0001 for both). Conclusion: In our cohort of patients with unknown cerebral ischemia monitored with ILR for AF recording, LA mechanical and electrical early subclinical changes identified patients at high risk of AF occurrence. This observation may have clinical implications, as better prediction of AF may help to identify those at highest risk and might assist in guiding therapy.