Arsanjani, Reza

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.

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.

Background: Among cardiac amyloidosis subtypes, transthyretin cardiac amyloidosis (ATTR) has gained increased recognition with the development of disease-specific therapies. Tafamidis, a selective oral stabilizer of the transthyretin tetramer, has emerged as an effective treatment. In the broader heart failure landscape, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have become cornerstone therapies across the ejection fraction spectrum, improving survival and reducing hospitalizations in both HFrEF and HFpEF. However, the clinical benefit of combining Tafamidis with SGLT2i in ATTR remains largely unknown. Hypothesis: Combination therapy with Tafamidis and SGLT2i provides added clinical benefits in patients with ATTR cardiac amyloidosis. Methods: This retrospective cohort study included adults with confirmed ATTR cardiac amyloidosis diagnosed via 99mTc-pyrophosphate scintigraphy and treated with Tafamidis alone or with an SGLT2i across three academic centers from January 2019 to February 2025. Baseline characteristics and outcomes were collected from medical records. The primary endpoint was all-cause mortality. Kaplan-Meier analysis and multivariable Cox proportional hazards modeling were used, adjusting for age, sex, atrial fibrillation, diabetes, hypertension, hyperlipidemia, ejection fraction (EF), and glomerular filtration rate (GFR). Results: Among the 1,211 patients included in the 3-year follow-up analysis,946 received Tafamidis monotherapy and 265 received a combination of Tafamidis and an SGLT2i. The mean age of the cohort was 71.9 years (SD ±9.4), and 87.3% were male. A total of 142 mortality events occurred, with a higher cumulative mortality rate observed in the tafamidis-only group (16.3%) compared to the combination group (9.4%) (log-rank p = 0.042). In the multivariable Cox proportional hazards model, combination therapy with Tafamidis and an SGLT2i was independently associated with a significantly lower risk of mortality (adjusted HR =0.576, 95% CI:0.334–0.992, p =0.04). Additionally, increasing age (HR =1.049, 95% CI:1.024–1.074, p < 0.001) was associated with higher mortality, while EF(HR =0.971, 95% CI:0.958–0.984, p< 0.001) and GFR (HR =0.975, 95% CI:0.965-0.985, p< 0.001) were with lower mortality. Conclusion: Combination therapy with Tafamidis and SGLT2i was associated with improved survival compared to Tafamidis alone in ATTR cardiac amyloidosis. Further prospective trials are needed to validate these findings and guide therapy optimization.

Background: High serotonin from neuroendocrine tumors (NETs) can result in carcinoid heart disease (CaHD) with severe valve dysfunction, often requiring valve replacement surgery. Lutetium-177 (Lu-177), a targeted radioactive isotope therapy, is increasingly utilized in the treatment of NETs; however, there is limited data on its impact on bioprosthetic heart valves (BHVs) in CaHD. Methods: A retrospective review was conducted on all patients with stage IV metastatic NET who underwent BHV replacement at three tertiary centers in the United States. Patients were stratified by Lu-177 therapy, administered after valve replacement. A propensity matched cohort of CaHD patients with BHV who did not received Lu-177 was curated including age, sex, and baseline left ventricular ejection fraction. Serial transthoracic echocardiograms (TTEs) following surgery were evaluated for progression of BHV degeneration; rise in mean gradient or increase in grade of prosthetic/periprosthetic regurgitation (grade increase of ≥1 out of 5), from first TTE following surgery (TTE1) to most recent TTE (TTE2). Analysis was performed at the level of individual valves, recognizing that some patients had more than one valve implanted. To account for changes in Lu-177 exposure over time, we constructed a time-varying Cox proportional hazards model. Accounting for non-independence of multiple valves within the same patient, a clustered Cox model was fitted using robust standard errors. Mortality was compared between patients exposed to Lu-177 therapy and those not exposed. Results: 184 patients were identified, mean age 60.4 ± 10.3 years, 53.3 % male. Of these, 16 patients had Lu-177 therapy, with 45 individual BHVs within this group. Patients in the control group had a total of 60 BHVs. Across a median of 2.09 years [0.77-5.01] between TTE1 and TTE2, BHVs exposed to Lu-177 therapy demonstrated an increased risk of BHV degeneration (HR=2.44, 95% CI 1.05–5.69, p=0.038), accounting for the time between TTE1 and administration of Lu-177 and the non-independence of multiple BHVs within the same patient. There was no significant difference in mortality between the two cohorts (p=0.440). Conclusions: BHVs in patients with CaHD exposed to Lu-177 therapy demonstrated an increased risk of degeneration. These findings suggest an association between Lu-177 treatment and accelerated prosthetic valvular deterioration, warranting further investigation and close monitoring in this patient population.

Introduction: Elevated lipoprotein(a) [Lp(a)] levels (≥30 mg/dL or ≥50 mg/dL) have been associated with increased risk of cardiovascular diseases (CVD), including myocardial infarction and aortic stenosis. However, its association with all-cause mortality (ACM) in the setting of primary prevention remains unclear, with conflicting evidence regarding the cutoff associated with increased mortality risk. Objective: To assess the association between elevated Lp(a) and risk of ACM in the context of primary prevention. Methods: In this retrospective cohort study, we included adult patients (≥18 years old) who had at least one measurement of Lp(a) at any of the three Mayo Clinic sites between 2007 and 2024, with no history of CVDs (i.e., coronary artery disease, ischemic stroke/transient ischemic attack, or peripheral arterial disease) at the time of Lp(a) measurement. Lp(a) levels were categorized based on the following percentiles: ≤50th percentile (≤11.6 mg/dL), 50th to 80th percentiles (11.6–46.6 mg/dL), 80th to 90th percentiles (46.6–75 mg/dL), 90th to 95th percentiles (75–100 mg/dL), and >95th percentile (>100 mg/dL). Survival probabilities up to 15 years were compared across Lp(a) percentile categories using the Kaplan–Meier estimator and log-rank test. Additionally, univariable and multivariable Cox regression analyses were conducted to adjust for potential CV confounders and to quantify this association. Results: A total of 42,770 patients (median age: 53 years and 54% males) were included. We found no significant difference in survival probabilities between the Lp(a) categories based on the overall log-rank test (p=0.12; Figure 1A ). In the univariable analysis, only patients with Lp(a) >95th percentile (>100 mg/dL) had a statistically significant higher risk of ACM [hazard ratio (HR): 1.37; 95%CI: 1.07–1.74; p=0.012], compared to patients with Lp(a) <50th percentile (<11.6 mg/dL). Similarly, after adjusting for potential CV risk factors, only those with Lp(a) >95th percentile (>100 mg/dL) showed a significantly higher risk of ACM (adjusted HR: 1.37; 95%CI: 1.07–1.75; p=0.012, Figure 1B ). Conclusion: In the setting of primary prevention, only very high Lp(a) levels (≥100 mg/dL) were independently associated with increased risk of ACM, suggesting that higher Lp(a) thresholds may be more relevant for identifying individuals at increased risk of ACM than the conventional ≥50 mg/dL cutoff.

Abstract Aims Left ventricular assist devices (LVADs) are a critical intervention for advanced heart failure (HF), serving as destination therapy or bridge to transplantation. Obesity and diabetes impact outcomes in patients with LVADs. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) demonstrate cardiovascular benefits; however, their role in patients with LVADs remains underexplored. We evaluated the association of GLP1-RA therapy with cardiovascular outcomes in patients with LVADs. Methods This retrospective cohort study used the TriNetX database, a research network database from 98 healthcare organizations. We queried for all adult LVAD recipients (≥18 years) and were stratified into GLP1-RA users and non-users. Propensity score matching (PSM) (1:1) balanced demographics, comorbidities, medication use and laboratory data. Outcomes included heart transplantation rates, heart failure hospitalizations, all-cause mortality, all-cause hospitalizations and cardiovascular events. Logistic regression models were used to estimate adjusted odds ratios (aOR). Results After PSM, we included a total of 1036 adult LVAD recipients (518 GLP1-RA users, 518 matched non-users) with a mean follow-up time of 311.6 ± 98.4 days for the GLP1-RA cohort and 304.0 ± 111.5 days for the non-GLP1-RAs cohort. Mean age was 56.7 ± 12.2 years in the GLP1-RA cohort and 58.0 ± 12.5 years in the non-GLP1-RA cohort. Females comprised 28.0% of both cohorts while White patients represented 52.1% of the GLP1-RA group and 53.1% of the non-GLP1-RA group. GLP1-RA users had higher heart transplantation rates [n = 98 (18.9%) vs. n = 44 (8.5%); aOR 2.514 (95% CI: 1.720–3.673)]. Acute HF events and all-cause hospitalizations were lower among GLP1-RA users compared with non-users [n = 288 (55.6%) vs. n = 357 (68.9%); aOR 0.565 (95% CI: 0.438–728) and n = 324 (62.5%) vs. n = 390 (75.3%); aOR 0.548 (95% CI: 0.420–0.716)]. No differences were observed when comparing the GLP1-RA cohort with the non-GLP1-RA cohort in regard to all-cause mortality [n = 32 (6.2%) vs. n = 44 (8.5%); aOR 0.709 (95% CI: 0.442–1.138)], stroke [n = 42 (8.1%) vs. n = 58 (11.2%); aOR 0.700 (95% CI: 0.461–1.062)] or cardiac arrest [n = 18 (3.5%) vs. n = 17 (3.3%); aOR 1.061 (95% CI: 0.541–2.082)]. Conclusions GLP1-RA therapy in patients with advanced HF and LVADs is potentially associated with improved heart transplantation rates while decreasing hospitalization and acute HF event rates.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity, mortality, and healthcare expenses. Meanwhile, effective management of AF requires a comprehensive, patient-centered approach that includes risk factor modification, rate and rhythm control strategies, and prevention of thromboembolic events. Multidisciplinary AF clinics have emerged as a model for comprehensive management to improve patient outcomes and reduce healthcare burden. This review discusses the rationale, structure, benefits, challenges, and future directions of multidisciplinary AF clinics, emphasizing their role in optimizing AF management.