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Key Points Atrial fibrillation after kidney transplantation is common and is associated with poor prognosis. Artificial intelligence applied to 12-lead electrocardiograms pretransplant accurately predicts the risk of new-onset atrial fibrillation in our cohort. High-risk artificial intelligence electrocardiography score was independently associated with increased risk of mortality and allograft failure. Background Incident atrial fibrillation (AF) is common after kidney transplantation (KTx) and is associated with worse clinical outcomes. Artificial intelligence electrocardiography (AI-ECG) algorithms have demonstrated efficacy in predicting risk of new-onset AF in the general population; however, their prognostic value in KTx recipients is relatively unknown. Methods Retrospective analysis was conducted on KTx recipients without AF, with at least one pretransplant ECG between 2011 and 2021 across three tertiary centers in the United States (Mayo Clinic sites in MN, AZ, and FL). A previously validated AI-ECG algorithm estimated the probability of incident AF for each patient. Based on AI-ECG probabilities, patients were categorized into high-risk and low-risk groups, with the optimal AI-ECG score cutoff determined. The incidence of new-onset AF, allograft failure, and mortality was compared between groups. Results Overall, 6246 patients (age 53.5±13.8 years; 58.9% male) were included. Pretransplant AI-ECG probability of AF ≥5% was the optimal cutoff for high risk of incident AF (sensitivity 72%, specificity 62%). High-risk scores were associated with true new-onset AF at 30 days (adjusted hazard ratio [aHR], 2.89; 95% confidence intervals [CI], 2.05 to 4.09; P < 0.001), 3 years (aHR, 2.54; 95% CI, 1.99 to 3.26, P < 0.001), and 5 years post-transplant (aHR, 2.48; 95% CI, 1.99 to 3.09, P < 0.001). High-risk AI-ECG scores were also associated with increased mortality (aHR, 1.56; 95% CI, 1.30 to 1.88, P < 0.001) and overall allograft failure (aHR, 1.50; 95% CI, 1.30 to 1.75, P < 0.001) through the 5-year follow-up. Conclusions This pretransplant AI-ECG parameter identified patients at increased risk of new-onset AF post-KTx and provided prognostic utility. Overall, this easy to obtain tool allows for risk stratification of patients who may benefit from closer monitoring, targeted risk factor modification, and early intervention.

Abstract Aims Pre-capillary pulmonary hypertension (PHTN), typically due to intrinsic pulmonary pathology, requires right heart catheterization (RHC) for diagnosis. ePLAR, the echocardiographic pulmonary to left atrial ratio [calculated: tricuspid regurgitation maximum velocity (TRVmax) divided by mitral valve E to e′ wave ratio (E/e′)], has been demonstrated as a promising non-invasive surrogate for characterization of pre-capillary PHTN. As such, this study aimed to further evaluate the diagnostic utility of ePLAR in a large cohort of patients with PHTN. Methods and results All RHCs between 2018 and 2023 across three tertiary centres were retrospectively reviewed. Patients with PHTN were characterized as pre-capillary or post-capillary (isolated or combined). Concurrent ePLAR was calculated. ROC analysis evaluated the accuracy of ePLAR in detecting pre-capillary PHTN. Overall, 2235 patients had PHTN by RHC, mean age 63.5 ± 14.7 years, 53.5% male. Of these, 43.3% had pre-capillary PHTN. ROC analysis demonstrated ePLAR to have good accuracy in detection of pre-capillary PHTN (AUC 0.760), with a cutoff of 0.20 m/s demonstrating a sensitivity and specificity of 77% and 60% respectively. This persisted on sensitivity analysis for contemporaneous investigations and for right ventricular function. Conclusion In this large cohort, ePLAR was validated as an accurate tool for identifying patients with pre-capillary PHTN. This widely available, non-invasive, and reproducible parameter can have an important role in the work up of PHTN and may guide the need for invasive testing.

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.

Background Immune‐checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI‐related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI‐treated patients are limited. Methods All patients treated with ICI who had hs‐TnT (high‐sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs‐TnT elevation were assessed. Risks of cardiac events were compared across hs‐TnT elevation causes. Results Of 5423 patients treated with ICI, 1669 had post‐ICI hs‐TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1‐year follow‐up. Hs‐TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7–238.0], P <0.001), followed by hs‐TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs‐TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4–15.3], P <0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events. Conclusions Hs‐TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs‐TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.

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.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but may increase thrombotic risk through immune-mediated inflammation. While venous thromboembolism is a known complication in cancer, real-world data quantifying the incidence of pulmonary embolism (PE) and deep venous thrombosis (DVT) specifically in ICI-treated patients remain limited. Methods: We conducted a retrospective cohort study of cancer patients treated with ICIs at a tertiary institution from 2011 to 2022. Electronic health records were reviewed to identify cases of PE and DVT, along with baseline characteristics and clinical outcomes at one-year follow-up. Rates of PE and DVT were compared to those reported in the literature. Time-dependent Cox regression analyses were performed to assess associations of PE and DVT with one-year all-cause mortality and heart failure (HF), defined as a new diagnosis and/or HF exacerbation/hospitalization. Results: Among patients treated with ICI, the incidence of PE and DVT was 10.6% and 8.3%, respectively. These rates are higher than those reported in several prior studies, where PE incidence in patients treated with ICI typically ranged from 3% to 6% and DVT incidence from 3% to 5%. A history of valve disease, lung cancer, and treatment with pembrolizumab or durvalumab were more frequently observed among patients with PE, whereas pembrolizumab use was most prevalent among those who developed DVT. In time-dependent Cox regression analyses, PE was significantly associated with increased one-year all-cause mortality (HR: 2.62, 95% CI: 2.12–3.23, p < 0.001) and showed a trend toward increased HF (HR: 1.63, 95% CI: 0.96–2.75, p = 0.070). Similarly, DVT was also associated with significantly higher one-year all-cause mortality (HR: 2.63, 95% CI: 2.10–3.31, p < 0.001) and a significantly greater risk of HF (HR: 1.80, 95% CI: 1.03–3.15, p = 0.040). Conclusion: In this real-world cohort study, PE and DVT were more frequent than previously recognized in ICI-treated cancer patients and were associated with significantly increased risks of all-cause mortality and heart failure. Conditions such as valve disease, lung cancer, and specific ICI therapies (e.g., pembrolizumab or durvalumab) may help identify patients at higher thrombotic risk. These findings underscore the importance of vigilant thrombotic risk assessment and may support the need for proactive monitoring or prevention strategies in high-risk patients receiving ICI therapy.