Lankenau Heart Institute

We report our initial cases of robotic left atrial appendage occlusion (LAAO) device deployment. From June 2021 to December 2024, all consecutive patients undergoing robotic-assisted LAAO (isolated or with robotic-assisted CABG) using an epicardial clip were enroled. The study protocol was approved by the Institutional Review Board (IRB 45CFR164.512). A total of 28 patients were included, 22 of which underwent a concomitant CABG. Transesophageal echocardiogram confirmed excellent exclusion of the LA appendage in all but one patient. There were no postoperative strokes, myocardial infarctions, reoperation for bleeding, unplanned revascularisation, or deaths. At a median of 1.4 [0.9-1.8] years, there was 1 non-cardiac mortality (cancer) and 1 stroke. Nine (32.1%) patients were off OAC, while 21 (75.0%) were off class I-III antiarrhythmic drugs. These early results show optimal stroke prevention outcomes, considering the high-risk level of the patients. Longer follow-up is warranted to confirm these outcomes.

ABSTRACT Background Cell polarity orchestrates spatial organization within tissues influencing cellular processes such as adhesion, proliferation, and differentiation. While the role of polarity proteins is well-established in epithelial systems, their function in mammalian cardiomyocytes remains poorly understood. Global deletion of the polarity protein, Llgl1, has been shown to impair cardiac trabeculation and disrupt cardiomyocyte junctions in zebrafish. Here, we investigate the role of Llgl1 in mammalian cardiomyocyte function. Methods We developed a mouse model whereby Llgl1 is deleted from cardiomyocytes (Llgl1 CKO ) and assessed cardiomyocyte intercalated disc integrity, cell cycle activity, cardiac function, and electrophysiology. We subjected mice to myocardial infarction to test if permanent Llgl1 deletion, or inducible Llgl1 deletion in adult cardiomyocytes (Llgl1 TamCKO ), influences the cardiac injury response. We performed RNAsequencing and in vitro knockdown and viral overexpression experiments to delineate the mechanisms by which Llgl1 influences cardiomyocyte phenotypes. Results Llgl1 CKO mice display disrupted intercalated disc integrity indicated by reduced protein density at cardiomyocyte junctions, associated with electrical conduction defects that manifest as ventricular arrhythmia. Furthermore, Llgl1 CKO mice display enhanced cardiomyocyte cell cycle activity extending into adulthood. Llgl1 CKO mice and mice whereby Llgl1 is deleted by tamoxifen induction in adulthood both show improved cardiac function and reduced scar size following myocardial infarction. Mechanistically, Llgl1 alters mechanotransduction and cell cycle pathways in the heart, and regulates proper localization of N-cadherin to the cell membrane, a process that is optimized by phosphorylation of five serine residues at the C-terminus of Llgl1. Conclusions We elucidate a key role for Llgl1 in establishing proper intercalated disc integrity in mammalian cardiomyocytes. Disruption of intercalated discs and mechanotransduction via Llgl1 knockout is associated with cardiac arrhythmia, elevated cell cycle activity and resistance to cardiac injury. These studies shed light on mechanisms underlying intercalated disc establishment and connect disrupted cardiomyocyte junctional integrity with enhanced cell cycle activity.

Iatrogenic aortic regurgitation after mitral valve surgery is the consequence of either direct stitching-related perforation or indirect distortion of aortomitral fibrous continuity by the mitral ring/prosthesis. This review aims at describing the reported cases of iatrogenic aortic valve regurgitation following mitral valve surgery, focusing primarily on its management. PubMed, ScienceDirect, DOAJ, and Cochrane databases were searched from inception until December 2023 for case reports and case series describing iatrogenic aortic valve regurgitation following mitral valve surgery. The literature review found 17 articles describing 20 cases of new onset aortic valve regurgitation after mitral valve surgery. Among them, 5 patients did not undergo reoperation, either due to medical decision or patient refusal. The non-coronary cusp was predominantly affected (11 cases), the left coronary cusp involved in 4 cases, and a mixed mechanism occurred in 5 cases. Subsequent surgical interventions included aortic valve replacements in 5 cases and aortic valve repair in 4 cases. A suggested management decision algorithm is finally proposed. Iatrogenic aortic valve regurgitation after mitral valve surgery remains an unfortunate complication. Attention should be given to prevent this complication. Intraoperative transesophageal echocardiography plays a crucial role for early detection. Management strategies vary from medical therapy to surgical interventions. The reparative strategy requires a surgical procedure associated with significant mortality.

There is limited knowledge of physicians' antiarrhythmic drug (AAD) treatment practices for patients with atrial fibrillation and adherence to guidelines in European countries. An online survey (n=321) of cardiologists, cardiac electrophysiologists and interventional electrophysiologists was conducted in Germany (DE; n=83), Italy (IT; n=95), Sweden (SE; n=60) and the United Kingdom (UK; n=83) including 96 questions on treatment practices. ESC guidelines were the most important non-patient factor influencing treatment practice (55-72%). However, while amiodarone was frequently (88-93%) used in heart failure with reduced left ventricular ejection fraction, it was also a typical treatment choice for minimal/no-structural heart disease (SHD) (28%), particularly in UK. Other deviations from guidelines were the use of class 1C drugs in coronary artery disease (CAD) and other SHD, and use of sotalol in left ventricular hypertrophy and renal impairment. In-hospital initiation of sotalol was low, with the exception of SE. Sotalol (16-41%) and dronedarone use (10-54%) in CAD varied among countries. For frequent, symptomatic paroxysmal AF, ablation was generally favoured, but AADs were preferred by 53% in SE. In asymptomatic or subclinical AF, AADs were used by 41% (range: 22-60%), ablation by 11% (range 2-18%). In contrast to guidelines that prioritize safety, anticipated efficacy was more important (51%) than safety (31%) when selecting AADs. Despite recognizing the importance of guidelines, deviations in AAD use were common with the potential to compromise patient safety. These findings indicate the need for more educational support for optimal AAD selection in AF management.

Dronedarone and sotalol are antiarrhythmic drugs (AADs) recommended in similar populations per atrial fibrillation (AF) guidelines; however, comparative safety data are limited. The goal of this study was to assess the safety of dronedarone vs sotalol for treatment of AF in AAD-naive patients. This was a prespecified noninterventional meta-analysis of 4 retrospective observational cohort studies from 4 databases (Optum Clinformatics Data Mart, Merative MarketScan, Veterans Health Administration Electronic Health Record, and the Swedish National Patient Register) conducted by using one master protocol. Each analysis emulated the target trial using an active comparator (dronedarone vs sotalol), new user design with an as-treated approach. Primary outcomes were tested hierarchically for dronedarone vs sotalol: first for statistical significance of cardiovascular (CV) hospitalization, and then for statistical significance of ventricular arrhythmias. Propensity score matching (PSM) was used for confounding control, and negative control outcomes were used to assess residual confounding. Outcomes were evaluated by using Cox proportional hazards regression; meta-analysis was performed by using fixed effects models. The dronedarone and sotalol cohorts were well balanced within databases before and after PSM (after PSM mean age range: 62.5-70.9 years; mean CHA2DS2-VASc score range: 1.81-3.15). Negative control outcomes exhibited little-to-no evidence of residual confounding. Meta-analysis found significantly lower rates of CV hospitalization (pooled HR: 0.91; 95% CI: 0.85-0.97) and ventricular arrhythmias (pooled HR: 0.77; 95% CI: 0.69-0.85) with dronedarone vs sotalol. In this retrospective meta-analysis, dronedarone exhibited significantly lower rates of CV hospitalization and ventricular arrhythmias compared with sotalol. These findings provide real-world evidence to support selection of the most appropriate first-line AAD for rhythm control in patients with AF.

Statin therapy is associated with an increased risk of hyperglycaemia and new-onset diabetes mellitus. The absolute increase in glycosylated haemoglobin (HgbA1c, a measure of average glucose level over the past three months) is typically small; dramatic and clinically relevant increases are rare. A 52-year-old man of South Indian descent with a history of hyperlipidaemia was started on rosuvastatin 40 mg daily for primary prevention of atherosclerotic cardiovascular disease. He did not have a history of diabetes mellitus. He developed polyuria and weight loss within weeks of starting statin therapy. Laboratory assessment was notable for HgA1c of 12.4% and LDL cholesterol of 84 mg/dL. Rosuvastatin was discontinued. He was not started on antidiabetic therapy as there was suspicion that statin therapy was the culprit for his HgbA1c rise. He soon had symptom resolution, and follow-up HgA1c 3 months later was 5.5%. Two years later, patient presented to the hospital with an acute coronary syndrome. He was discharged on rosuvastatin 40 mg daily and developed polyuria 1 week later. Rosuvastatin was discontinued, and atorvastatin 40 mg daily was initiated. Antidiabetic therapy was not started. He had resolution of his symptoms; follow-up HgA1c was below the diabetes threshold. Statins are associated with a small increased risk of developing diabetes mellitus. The beneficial effects of statins on cardiovascular events typically outweigh any increased risk conferred by hyperglycaemia. While high-intensity statin therapy is routinely used as initial therapy for secondary prevention, we have no documentation explaining the choice of high-intensity statin for primary prevention in this case.

This study aimed to compare early clinical and hemodynamic outcomes of transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis and large aortic annulus using either balloon-expandable valves (BEVs) or self-expanding valves (SEVs). A comprehensive search of PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was conducted through September 10, 2023, to perform a meta-analysis comparing the clinical outcomes of BEV versus SEV for large aortic annulus (annulus perimeter ≥ 80mm). Seven studies (one propensity-matched study and six observational studies) met our eligibility criteria, including a total of 2167 patients (BEV, 1521; SEV, 646). The rates of procedural stroke (pooled odds ratio 0.55, 95% confidence interval 0.32-0.98), valve embolization (0.11, 0.05-0.24), need for second valve implantation (0.21, 0.17-0.26), permanent pacemaker implantation (0.43, 0.28-0.67), and aortic regurgitation ≥ moderate (0.23, 0.08-0.68) were significantly lower in the BEV group. Conversely, postoperative transvalvular gradient was significantly lower in the SEV group (pooled standard mean difference 0.55, 0.12-0.98). Subgroup analysis with newer-generation valves also showed significant differences in the need for second valve implantation and permanent pacemaker implantation, as well as aortic regurgitation ≥ moderate, favoring BEVs. BEV provides better early outcomes in TAVR for large aortic annulus in terms of lower rates of stroke, valve embolization, need for second valve, permanent pacemaker implantation, and aortic regurgitation ≥ moderate. Conversely, SEV provides a better transvalvular gradient in the early period after TAVR. The online version contains supplementary material available at 10.1007/s12055-024-01770-1.