Abdelnabi, Mahmoud

Abstract Background/Introduction Patients with transthyretin cardiac amyloidosis (ATTR-CA) and atrial fibrillation (AF) have increased risk for left atrial thrombi, necessitating anticoagulation therapy if bleeding risk is not prohibitive. Limited data is available comparing the use of direct oral anticoagulants (DOACs) to warfarin in this population. Purpose To evaluate and compare clinical efficacy and safety outcomes of DOACs versus warfarin in patients with ATTR-CA and AF. Methods We conducted a retrospective cohort study using the TriNetX Network, which includes data from over 140 million patients, between 2014 and 2022. Adults (aged ≥18 years) with ATTR-CA and AF were identified. These patients were further categorized into two groups: one cohort which utilized DOACs for oral anticoagulation and the other cohort on warfarin. 1:1 propensity score matching (PSM) was utilized to balance baseline characteristics between the two cohorts. The primary outcome was rate of stroke, with secondary outcomes including all-cause death, all-cause hospitalizations, and acute heart failure exacerbations. Safety outcomes included intracranial hemorrhage, gastrointestinal hemorrhage, and hematuria. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Results Among 8,214 adults with ATTR-CA and AF, 5,774 patients were on a DOAC while 2,440 patients were on warfarin. After PSM, 2,425 patients were included in each group. The use of DOACs for AF in patients with ATTR-CA was associated with a significantly lower risk of ischemic stroke compared to warfarin (5.7% versus 7.3%, aOR 0.771 [95% CI, 0.612-0.971]) by the end of the one year follow up. There were no differences in all-cause mortality (19.8% versus 21%, aOR 0.927 [95% CI, 0.806-1.066]), all-cause hospitalizations (19.2% versus 21.6%, aOR 0.863 [95% CI, 0.624-1.195]) or heart failure exacerbations (43.6% versus 46%, aOR 0.906 [95% CI, 0.809-1.015]). Safety outcomes favored DOACs over warfarin, with a lower risk of intracranial hemorrhage (4.5% versus 7.8%, aOR 0.565 [95% CI, 0.444-0.720]), and comparable rates of GI hemorrhage and hematuria. Conclusions DOACs may be safely used in ATTR-CA patients with AF, offering a lower risk of stroke compared to warfarin and a more favorable safety profile. These findings emphasize the potential advantages of DOACs in this population and underline the need for prospective studies to validate these results.

Background To compare the effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) versus bariatric surgery on cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction and obesity. Methods Using the TriNetX research network, we conducted a retrospective cohort study of adults (aged ≥18 years) with HF with preserved ejection fraction and obesity (body mass index >30 kg/m 2 ) from 2017 to 2022. Patients were categorized into 2 cohorts: those receiving GLP‐1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) was used to balance baseline characteristics. Primary outcomes included acute HF events and all‐cause hospitalizations. Secondary outcomes included all‐cause death, myocardial infarction, stroke, and follow‐up body mass index. Cox proportional hazard models were used to estimate hazard ratios (HRs). Results A total of 2747 patients were included per cohort (mean age, 68 years). GLP‐1 RA therapy was associated with lower incidence of acute HF events (38.9% versus 44.6%; HR, 0.78 [95% CI, 0.72–0.85]), all‐cause death (11.1% versus 14.8%; HR, 0.71 [95% CI, 0.61–0.82]), and all‐cause hospitalizations (66.4% versus 77.3%; HR, 0.62 [95% CI, 0.58–0.66]). Rates of myocardial infarction (13.8% versus 13.4%; HR 0.99 [0.86–1.14]) and stroke (9.7% versus 10.7%; HR, 0.87 [0.74–1.02]) were similar between groups. Mean body mass index at follow‐up was 38.0 in the GLP‐1 RA cohort versus 37.7 after bariatric surgery ( P =0.34). Hemoglobin A 1c at follow‐up was higher in the GLP‐1 RA group (7.4 versus 6.8; P <0.001). Conclusions In patients with HF with preserved ejection fraction and obesity, GLP‐1 RA therapy was associated with improved outcomes compared with bariatric surgery, supporting the need for prospective trials to evaluate GLP‐1 RAs as a therapeutic alternative.

Positive inotropic agents have an important role in the management of acute decompensated heart failure patients with reduced cardiac output and poor end-organ perfusion. However, despite their acute hemodynamic benefits, the role of inotropes in the management of chronic advanced heart failure remains limited to palliative therapy or as a bridging strategy to mechanical support or heart transplantation. Milrinone is one of the most common inotropic agents used in advanced heart failure to provide symptomatic relief and improved hemodynamics. This review discusses the current evidence of milrinone’s efficacy, indications, outcomes in advanced heart failure, evidence gap, and future directions.

Ventricular arrhythmias after electrical cardioversion for AF are rare. Most of these arrhythmias are related to QT prolongation, resulting from marked and sudden slowing of heart rates, treatment with Class III antiarrhythmic drugs or other QT-prolonging medications, and the ventricular repolarisation remodelling effect of electrical cardioversion. A case of polymorphic ventricular tachycardia post-cardioversion of rapid AF in a patient with tachycardia-induced cardiomyopathy and the use of amiodarone is reported.

Abstract Aims We evaluated clinical outcomes with GLP-1 RA use post-TAVI in patients with T2D. GLP-1 receptor agonists (GLP1-RAs) lower cardiovascular risk in type 2 diabetes (T2D), but their impact in patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), remained unexplored. Methods and results We conducted a retrospective cohort study using the TriNetX network, including 25 184 adults (≥18 years) with T2D who underwent TAVI (2015–2023). Patients were stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for events from one-month post-TAVI until the most recent follow-up. PSM yielded 1101 patients per group, with a mean age of 73 years and 39% female. Mean follow-up duration was 2.2 ± 1.1 and 2.6 ± 1.8 years for GLP1-RA users and non-users, respectively. GLP1-RA use was also associated higher survival probability (HR: 0.708 [95% CI: 0.583–0.859]), and lower rates of all-cause hospitalization (HR: 0.790 [95% CI, 0.706–0.885]), major cardiovascular events (HR: 0.849 [95% CI: 0.749–0.963]), and acute heart failure exacerbation (HR: 0.785 [95% CI: 0.677–0.909]), acute kidney injury (HR: 0.843 [95% CI: 0.719–0.988]), and major kidney events (HR: 0.665 [95% CI: 0.510–0.866]). No differences were observed in acute myocardial infarction, cerebral infarction, or cardiac arrest. Conclusion In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiorenal outcomes. However, these findings are limited by the observational design, high comorbidity burden, lack of data on medication compliance, and specific cause of death. Prospective trials are warranted to confirm these benefits.

Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways. Beyond direct immunomodulators, GLP-1 receptor agonists and SGLT2 inhibitors provide both cardioprotective and anti-inflammatory benefits, reinforcing their expanding role post-ACS. Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic developments.

Background Elevated lipoprotein(a) [Lp(a)] and low high-density lipoprotein-cholesterol (HDL-C) are established cardiovascular (CV) risk factors, but their combined impact on mortality and sex differences remains unclear. Methods This retrospective study analyzed 97 396 patients with measured Lp(a) and HDL-C. Groups were stratified by Lp(a) (≥50 vs. <50 mg/dl) and HDL-C [low (<40), optimal (40–60), high (>60 mg/dl)]. Mortality was assessed using the Kaplan–Meier curve and Cox models. Results Over a median of 5.9 years, 7794 deaths occurred. Compared to optimal HDL-C/low Lp(a) (reference), high HDL-C/low Lp(a) had the lowest mortality [adjusted hazard ratio (aHR): 0.85; 95% confidence interval (CI): 0.80–0.91], while low HDL-C/high Lp(a) had the highest risk (aHR: 1.55; 1.41–1.71). High HDL-C protective effect was insignificant with elevated Lp(a) (aHR: 0.98; 0.89–1.08). Sex-stratified analyses revealed divergent effects: women with high HDL-C/high Lp(a) retained the HDL-C protective effect (aHR: 0.82; 0.72–0.93), whereas men faced increased risk (aHR: 1.22; 1.05–1.42). Conclusion Elevated Lp(a) enhances mortality risk despite elevated HDL-C levels, with sex-specific differences: women retain mortality benefits from high HDL-C despite elevated Lp(a), whereas men with concurrent elevations in HDL-C and Lp(a) experienced mortality risks comparable to those with low HDL-C. Findings underscore sex-specific CV risk stratification incorporating HDL-C and Lp(a), challenging the HDL-C universal protective role.