Funding Acknowledgements Type of funding sources: None. Background Heart failure with reduced ejection fraction (HFrEF) is associated in about one third of patients with abnormal conduction of the cardiac electrical impulse, resulting in asynchronous activation of the ventricles and worsening of cardiac pump function. Cardiac resynchronization therapy via biventricular pacing (CRT) has demonstrated improvement in cardiac mechanical function. The pharmacological treatment of HFrEF with sacubitril/valsartan (ARNi) and glyphozines (iSGLT2) have been shown to significantly reduce mortality. Purpose The objective of our study was 1) to evaluate the effect of therapy with ARNi and iSGLT2 on the recovery of left ventricular ejection fraction (LVEF %) in a population affected by HFrEF and with CRT 2) to evaluate whether there are any differences in terms of improvement in LVEF among patients who introduced these drugs into therapy before CRT implantation and those who introduced them after. Methods This single-center retrospective study analyzed patients with HFrEF and CRTD. These patients in our center undergo regular follow-up with cardiology visit, ECG and echocardiography every 6 months. We analyzed clinical features, drug therapy, and echocardiographic data including LVEF. Patients were considered responders they had an increase in LVEF ≥ 5% or a decrease in end-systolic volume of 15% at 6 months. The data analysis was performed with the R software. Results 258 patients were included, 202 males (78%) with a mean age of 69.4 years, and 67.4% of them with ischemic HFrEF. Diabetes mellitus (68%), dyslipidemia (87%) and arterial hypertension (73%) were the most frequent comorbidities. Fifty-two percent of patients (133) were CRT responders and there was no difference in the proportion of responders between patients receiving ARNi and/or iSGLT2 therapy and those without (55% vs 47%; p=ns). The mean increase of LVEF was also similar between the two groups (+7.7% vs +10.3%; p=ns). In the group of patients taking ARNi or iSGLT2, no significant differences were found between patients taking these drugs already before CRT compared to those who started after. Conclusions In this population, HFrEF patients with CRT, therapy with ARNi or iSGLT2 does not affect the response to CRT.

Funding Acknowledgements Type of funding sources: None. Background Patients with atrial fibrillation (AF) have higher risk of ischemic stroke. Purpose We investigated whether AF patients experiencing an ischemic stroke have worse outcomes. Methods AF patients admitted to the stroke unit from 2018 to 2021 were included. The NIHSS and the modified Rankin Scale (mRS) score were calculated at the admission and at discharge. The neurological improvement was calculated as delta NIHSS (NIHSS at admission - NIHSS at discharge =Δdis). Results Six-hundred patients (45% men), mean age 69±13 years. Of these 75 had previous history of atrial fibrillation (AF) and 86 had AF during the hospitalization (46 both). Overall 115 had one of the two. Patients with AF had higher NIHSSad (14.5±7 vs 9.6±7; p<0.001) and NIHSS24 (10.4±8 vs 7.2±7; p<0.001) than patients without, however the neurological improvement was greater (Δdis -8.4±8 vs -5.1±6; p=0.004), indeed the NIHSSdis was similar (5.6±7 vs 4.1±6; p=0.1). Patients with AF also had a more impaired mRS before the ischemic event and at discharge (1.34±1.3 vs 0.58±1.1, p<0.001; 2.6±1.7 vs 1.8±1.9, p=0.005). Amongst AF patients with CHADVASC³2 in men and ³3 in women, 36% of them were taking antiplatelet therapy, 35% anticoagulants and 29% didn’t take any therapy. Of interest, no differences in the NIHSSad nor in the NIHSSdis were found between them and neither in the Δdis. As for the treatment of AF patients, patients who underwent to mechanical thrombectomy (MT) had higher NIHSSad (17± 5) compared to patients receiving intravenous thrombolysis (IV) or nothing (11± 7 and 12± 8) (p<0.001). The NIHSSdis was similar between the three groups however the Δdis was significantly higher in patients treated with mechanical thrombectomy (-12.5±6 vs 3.6±4; vs 3.1±8; p=0.003 and p<0.001 respectively). Conclusions Patients with AF experience more severe stroke, however the neurological recovery is greater than in patients without the arrhythmia. The treatment with antiplatelets or anticoagulants before the event does not reduce the severity of the stroke and does not influence the improvement of the NIHSS at discharge. The mechanical thrombectomy is more effective in reducing the neurological impairment.

BACKGROUND. The angiotensin receptor-neprilysin inhibitor (ARNi) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i) have improved the outcome of patients with heart failure and reduced ejection fraction (HFrEF). However, data characterizing their effectiveness after cardiac resynchronization therapy (CRT) implant are relatively scarce. This study investigated the impact of ARNi and SGLT2i treatment 1) on CRT response at 12 months 2) on the cardiac function and the clinical functional status (NYHA class) at mid- and long-term follow-up 3) on the cardiac and overall survival at long-term follow-up. METHODS AND RESULTS. HFrEF patients referred for CRT implant were enrolled in the study and were grouped by the ARNi/SGLT2i therapy. The first analysis investigated the synergistic impact of these drugs started at implant on 1-year CRT response and included all 172 patients enrolled. In order to evaluate whether the time of ARNi/SGLT2i initiation after CRT response assessment is meaningful, the second analysis considered 100 patients with a follow-up > 24 months. The median follow-up was 63.1 (confidence interval [CI] 95%, 52.7 - 73.8) months. At 1-year follow-up, 40 of 51 (78.4%) patients in ARNi or SGLT2i group and 66 of 121 (54.5%) in the no treatment group were classified as responders (p = 0.006). In multivariable analysis, ARNi/SGLT2i use was an independent predictor of CRT response (odds ratio, 5.38; CI 95%, 2-16.2; p = 0.001). At mid-term follow-up (median time [interquartile range, IQR] 40.6 [25.2; 58.3] months), 61 patients started to assume these drugs. NYHA functional class improved in 23 (37.7%) patients and decreased in only 2 (3.3%) in ARNi/SGLT2i patients vs 13 (33.3%) in no treatment group (p < 0.001). ARNi and SGLT2i improved significantly also the ? LVEF, with a median [IQR] increase of 4 [2; 8] % compared to the no treatment group -1.8 [-4; 0.2] % (p < 0.001) and were independently associated with a NYHA functional class II or I at long-term (hazard ratio [HR], 3.67; CI 95%, 1.37-10.2; p < 0.001). Their estimated effectiveness was consistent over the entire follow-up period (Schoenfeld residuals test, p = 0.10), although without reaching statistical significance effects on cardiovascular survival (HR, 0.61; CI 95%, 0.25-1.50; p = 0.22). CONCLUSIONS. The ARNi and SGLT2i treatment in CRT patients improves the clinical and echocardiographic response at 12-month and long-term follow-up, independently from the time of initiation. These drugs also confer benefit on survival, however further studies are needed to confirm these data.