Leadless pacemaker: State of the art and incoming developments to broaden indications.

Theleadless pacemaker (LLPM) therapy has been developed in recent years to overcome the transvenous lead and device pocket-related complications. The LLPMs now available are self-contained right ventricular pacemakers and are limited to single-chamber ventricular pacing modality. This literature review deals with the current status of LLPM technology and current areas of clinical applicability. The safety and efficacy outcomes published from randomized clinical trials and real world registries are analyzed and compared with historical conventional transvenous pacemaker data. Furthermore, new pacing modalities and future perspectives to broaden the clinical use and cover most of pacing indications are discussed. Due to the overall safe and effective profile in the short term and intermediate term, also in fragile patients, the LLPM use is constantly growing in daily clinical practice. Actually, it can be considered a landmark innovation, through which a new era of cardiac pacing has begun.

Prognostic impact of the updated 2018 HFA-ESC definition of advanced heart failure: results from the HELP-HF registry.

AIMS: The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high-risk HF. METHODS AND RESULTS: The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk 'I NEED HELP' marker, evaluated at four Italian centres between 1st January 2020 and 30th November 2021. Patients meeting the HFA-ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high-risk 'I NEED HELP' marker were included (mean age 75.1 ± 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%-50%]). Among them, 193 (16.8%) patients met the HFA-ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA-ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82-2.74, p < 0.001). The prognostic impact of the HFA-ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57-2.50, p < 0.001). CONCLUSIONS: The HFA-ESC advanced HF definition had a strong prognostic impact in a contemporary, real-world, multicentre high-risk cohort of patients with HF.

Cardiac conduction defects.

Defects in cardiac electric impulse formation or conduction can lead to an irregular beat (arrhythmia) that can cause sudden death without any apparent cause or after stress. In the following sections, we describe the genetic disorders associated with primary cardiac conduction defects, primarily caused by mutations in ion channel genes. Primary indicates that these disorders are not caused by drugs and are not secondary to other disorders like cardiomyopathies (described in the next section).

Real-world 2-year outcome of atrial fibrillation treatment with dabigatran, apixaban, and rivaroxaban in patients with and without chronic kidney disease.

Patients with non-valvular atrial fibrillation (NVAF) and chronic kidney disease (CKD) are at increased risk of stroke and bleeding. Although direct oral anticoagulant (DOAC) trials excluded patients with severe CKD, a growing portion of CKD patients have been starting DOACs and limited data from real-world outcome in this high-risk setting are available. The INSigHT registry included 632 consecutive NVAF patients that started apixaban (256 patients, 41%), dabigatran (245, 39%) and rivaroxaban (131, 20%) between 2012 and 2015. Based on creatinine clearance, two sub-cohorts were defined: (1) non-CKD group (CrCl 60-89 mL/min, 413 patients) and (2) CKD group (15-59 ml/min, 219). Compared to non-CKD patients, those with CKD, were at higher ischemic (CHA2DS2-VASc 4.5 vs 2.9, p < 0.001) and hemorrhagic risk (HAS-BLED 2.4 vs 1.8, p < 0.001). At 2-year follow-up, the overall ISTH-major bleeding and thromboembolic event rates were 5.2% and 2.3% and no significant difference between non-CKD and CKD patients for both efficacy and safety endpoints were observed. In non-CKD patients, the 2-year ISTH-major bleeding rates were higher in rivaroxaban group (HR 2.9, 95% CI 1.1-7.3; p = 0.047) while dabigatran showed non-significant excess in thromboembolic events (HR 4.3, 95% CI 0.9-20.8; p = 0.068). In CKD patients, a significantly higher rate of thromboembolic events was observed in rivaroxaban (HR 6.3, 95% CI 1.1-38.1; p = 0.044). This real-world, non-insurance database registry shows remarkable 2-year safety and efficacy profile of DOACs even in patients with moderate to severe CKD. Head to head differences between DOACs are exploratory, hypothesis generating and warrant further investigation in larger studies.

Two-year cardiac mortality after MitraClip treatment of functional mitral regurgitation in ischemic and non-ischemic dilated cardiomyopathy.

BACKGROUND: MitraClip implantation has evolved as a new tool for treatment of inoperable or high-risk patients with severe functional mitral regurgitation (FMR) due to dilated cardiomyopathy (DCM). Limited data are available regarding MitraClip outcomes comparing patients with ischemic and non-ischemic DCM. METHODS: From 2008 to 2016, 314 patients received MitraClip for FMR at four institutions: Brescia, Zurich and Milan. Patients were stratified according to MR aetiology in non-ischemic FMR (n = 99) and ischemic FMR (n = 215). Preoperative risk factors, operative variables and outcomes up to 2-year were evaluated. A multivariable Cox Proportional Hazards survival model with covariate adjustments was used to assess the relationship between FMR aetiology and 2-year cardiac mortality. RESULTS: As expected, patients with ischemic FMR had significantly more risk factors and comorbidities. Overall procedural success rate was 80% and in-hospital cardiac mortality was 3% without significant differences between aetiology. Two-year overall (25% vs. 19%, p = 0.574) and cardiac (18% vs. 16%, p = 0.990) mortality rates were comparable. No differences were detected in terms of re-hospitalization rates (32%), LVAD implantation (4.5%) and mitral valve surgery (1%). LVEF ≤ 25%, LVEDV > 216 ml, NT-proBNP ≥ 10.000 pg/ml and AF were the strongest baseline predictors of 2-year cardiac mortality. Greater improvements of 6MWT and NYHA functional class were observed in patients with non-ischemic FMR. CONCLUSIONS: The ischemic or non-ischemic aetiology of DCM did not affect in-hospital and 2-year cardiac mortality after MitraClip in patients with FMR. In case of unfavorable baseline clinical condition, the indication for MitraClip should be carefully weighed in favour of conservative medical therapy alone or left ventricular assist device.

Polymer-free amphilimus-eluting stent versus biodegradable polymer biolimus-eluting stent in patients with and without diabetes mellitus.

OBJECTIVES: This study sought to compare clinical outcome of polymer-free amphilimus-eluting stent (PF-AES) versus biodegradable-polymer biolimus-eluting stent (BD-BES) in "all-comer" diabetes mellitus (DM) and non-DM patients who underwent percutaneous coronary intervention. BACKGROUND: The PF-AES has shown promising preliminary results in patients with DM. METHODS: Data from 2 multicentre-national registries (the ASTUTE and the INSPIRE-1) were used to analyse 1776 patients stratified in non-DM and DM. A double 1:1 propensity-score matched analysis (PF-AES vs. BD-BES) was performed in each group to adjust for clinical and procedural characteristics. Primary stent-efficacy and stent-safety endpoints were 1-year target-lesion revascularization (TLR) and target-lesion failure (TLF, composed of cardiac-death, target-vessel myocardial infarction and any TLR). RESULTS: After propensity-score matching, 850 patients were stratified as non-DM (425 PF-AES/425 BD-BES) and 480 as DM patients (240 PF-AES/240 BD-BES). Both TLF (20 of 425 [5%] vs. 24 of 425 [6%]; Plog-rank=0.527) and TLR (9 of 425 [2%] vs. 18 of 425 [4%]; Plog-rank=0.079) were similar between PF-AES and BD-BES in non-DM patients. In DM, TLF (12 of 240 [5%] vs. 31 of 240 [13%]; Plog-rank=0.002) and TLR (9 of 240 [4%] vs. 21 of 240 [9%]; Plog-rank=0.019) were significantly lower in PF-AES compared to BD-BES. Upon multivariate analysis, the most powerful predictors of TLF were chronic kidney disease in non-DM (OR 4.24, 95% CI: 2.07-8.70, p<0.001) and stent type in DM patients (OR 2.76, 1.36-5.56, p=0.005). CONCLUSIONS: This matched-cohort study suggests that PF-AES has better safety and efficacy profile than BD-BES in patients with DM.