Nabi, Hussein Abdul

Background: Noncompaction cardiomyopathy (NCCM) is a distinct myocardial disorder associated with a high risk of ventricular arrhythmias and sudden cardiac death. Although implantable cardioverter-defibrillators (ICDs) are frequently used in this population, data on predictors of shock therapy remain limited. Aim: Evaluation of a large cohort of patients with NCCM and ICDs to identify incidence and clinical factors associated with ICD shock Methods: This retrospective cohort study included patients with confirmed NCCM between 2002 and 2023 at all Mayo Clinic sites. Baseline clinical data, genetic findings, cardiac imaging parameters, and device-related outcomes were collected through detailed chart review. Multivariable Logistic regression was used to identify independent predictors. Results: Among 145 patients with NCCM who received ICDs, the median age was 45 years (IQR: 34–56), with 75 (52%) female and 120 (83%) White. The median left ventricular ejection fraction (LVEF) was 35% (IQR: 22.5–47.5%), and the median follow-up from ICD implantation was 6.4 years (IQR: 2.9–11.0). Most ICDs (124, 85.5%) were implanted for primary prevention. Appropriate shocks were observed in 37 patients (25.5%), with 14 (9.8%) experiencing three or more appropriate shocks. Inappropriate shocks occurred in 15 patients (10.3%). Device-related complications were reported in 22 patients (15.2%), including infections in 4 (2.8%), lead fractures or dislodgement in 17 (11.9%), and pneumothorax in 1 (0.7%). Clinical predictors of shocks are illustrated in the figure. Conclusion: ICD therapy for NCCM patients prevented SCD in 25.5% of patients. Syncope, RBBB, troponin T >30 ng/L, and imaging-based apical trabeculations were independently associated with ICD shocks in patients with NCCM. These factors may aid in risk stratification and clinical decision-making.

Background: Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos syndrome (vEDS) are rare connective tissue disorders characterized by arterial fragility and early-onset vascular events. Stroke risk is elevated in both conditions, but data on stroke subtypes and anticoagulation use remain limited. Understanding the relationship between stroke mechanisms, arrhythmias, and antithrombotic therapy is crucial in these genetically vulnerable populations. Aim: To assess the prevalence and subtypes of stroke in patients with LDS and vEDS. Methods: A retrospective chart review was conducted across three Mayo Clinic sites. Patients with LDS and vEDS were identified using an electronic data extraction tool, followed by manual chart review for diagnostic confirmation. Stroke subtypes, ischemic, dissection-related, and hemorrhagic, were classified based on imaging findings and clinical documentation. Data on atrial arrhythmias, valve replacement status, and anticoagulation use (including warfarin and apixaban) were systematically collected and analyzed. Results: In the LDS cohort, 12 of 94 patients (12.8%) experienced a stroke: 8 ischemic (8.5%), 3 dissection-related (3.2%), and 1 hemorrhagic (1.1%). Atrial fibrillation or flutter was present in 7 patients (58.3%), 6 of whom had ischemic strokes. Among the stroke patients, 9 (75%) had prosthetic valves, 6 mechanical and 3 bioprosthetic, and 4 (33.3%) were on warfarin at the time of the event. In the vEDS cohort, 22 of 132 patients (16.7%) had strokes: 13 ischemic (9.8%) and 9 dissection-related (6.8%). No hemorrhagic strokes were observed. Atrial fibrillation or flutter was documented in 12 patients (54.5%), with 10 experiencing ischemic and 2 dissection-related strokes. Of these, 5 (22.7%) were on apixaban, 3 (13.6%) on warfarin, and 4 (18.2%) were not anticoagulated. None of the vEDS stroke patients had mechanical valves. Conclusion: Ischemic stroke is the most frequent cerebrovascular event in both LDS and vEDS, but dissection-related strokes are more common in vEDS. Atrial arrhythmias often precede ischemic events, yet anticoagulation use varies widely. One-third of dissection-related strokes occurred despite antithrombotic therapy, raising concerns about current management strategies. These findings support the need for syndrome-specific guidelines for stroke prevention, arrhythmia management, and anticoagulation in LDS and vEDS patients.

Background: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as a cause of acute coronary syndrome, particularly in young to middle-aged women. While most presentations are associated with preserved left ventricular ejection fraction (LVEF), a subset of patients present with acute systolic dysfunction. The characteristics of patients who recover their LVEF are not clearly defined. Methods: We retrospectively analyzed 495 patients with angiographically confirmed SCAD treated at three Mayo Clinic sites (Arizona, Rochester, and Florida) from 1994 to 2023. Patients with a prior history of myocardial infarction, coronary artery disease, and congenital heart disease were excluded. Baseline LVEF at SCAD presentation was categorized into <35%, 35–39%, 40–49%, and ≥50%. Follow-up LVEF was assessed by echocardiography performed between 30 days and 1 year post-SCAD. The primary outcome was improvement in LVEF to ≥50% at follow-up. Results: A total of 495 SCAD patients were included. At presentation, 26% had reduced LVEF: 6% had LVEF <35%, 5% had LVEF between 35–39%, and 15% had LVEF between 40–49%. Patients who did not normalize their EF at follow-up were slightly younger (45 vs. 48 years, p=0.04), were more likely to have had an in-hospital cardiac arrest (13% vs. 4%, p=0.01), required mechanical circulatory support during their care, and had SCAD involving the left main artery (11% vs. 2%, p=0.01). Predictors of EF normalization included SCAD which involved the obtuse marginals (15% vs. 4%, p<0.05). The group with the lowest EF at presentation had the highest probability of persistent EF <50% at follow-up (32% for those with LVEF <35%) while patients who had normal EF at presentation had a 6% chance of having EF <50% at follow-up (Figure 1). Conclusions: Our study shows that the majority of SCAD patients have normal EF at presentation. 80% of those with reduced EF at presentation will normalize at follow-up. Predictors of low EF at follow-up included dissection involving the left main artery, lower EF at SCAD presentation, in-hospital arrest and use of mechanical circulatory support.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by cholestasis and progressive fibrosis. While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30–40% of patients have an inadequate biochemical response, increasing the risk of disease progression. Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was the first second-line agent approved by the only Food and Drug Administration (FDA) and has demonstrated moderate biochemical efficacy but limited tolerability due to dose-dependent pruritus and safety concerns in cirrhosis. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies’ mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research into long-term clinical outcomes.

Thoracic aortic aneurysm and dissection (TAAD) encompasses a clinically heterogeneous group of diseases characterized by high morbidity and mortality. Genetic studies over the past two decades have significantly expanded our understanding of the molecular landscape underlying heritable TAAD, revealing contributions from multiple interconnected biological pathways. This review systematically summarizes more than 75 genes implicated in TAAD pathogenesis, categorizing them according to major mechanistic roles including TGF-β signaling, extracellular matrix remodeling, smooth muscle cell contractility and cytoskeletal regulation, cell–matrix and cell–cell adhesion, metabolic processes, ion transport, and transcriptional regulation. Special emphasis is placed on emerging genes with variable or overlapping clinical phenotypes, dual-mechanism candidates, and their implications for personalized clinical management, including surveillance and surgical intervention thresholds. The integration of molecular insights into clinical practice, along with cautious consideration of genes of uncertain significance, promises to enhance diagnostic precision and risk stratification in individuals and families affected by heritable aortic disease.

Bicuspid aortic valve (BAV) and thoracic aortic aneurysms and dissections (TAAD) are recognized in syndromic connective tissue diseases (CTD), but most cases occur sporadically. The extent to which non-syndromic BAV or TAAD predisposes to additional arteriopathies, particularly in younger individuals, remains unclear. We retrospectively analyzed 1438 patients (mean age = 48.0, 67.7% female), excluding those with CTDs. Participants were ≤60 years old and categorized by the presence of BAV and/or TAAD. We examined co-existing arterial pathologies, including fibromuscular dysplasia, spontaneous coronary artery dissection, abdominal aortic aneurysms (AAA), mesenteric, peripheral extremity, and carotid/cerebral arteriopathies. Overall, 44.6% had either BAV or TAAD, and 27.2% had multiple arteriopathies. While vascular diseases were frequently noted, odds ratios demonstrated no significantly increased risk of extra-aortic arteriopathies in the BAV or TAAD cohorts. AAA exhibited a non-significant trend toward higher prevalence in TAAD patients. These findings support current guidelines recommending targeted imaging (transthoracic echocardiography of the aortic root and ascending aorta) over comprehensive “head-to-pelvis” screening for non-syndromic BAV or TAAD patients without additional risk factors. Ongoing genetic analyses may elucidate whether particular variants predispose to multi-site aneurysms or dissections. Consequently, targeted surveillance remains appropriate, with broader imaging reserved for patients with genetic or clinical indicators of higher risk.