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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: HIV cardiomyopathy (HIV-CM) is associated with significant morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have benefits in heart failure (HF), but their role in the specialized population of HIV-CM is poorly understood. Methods: Patients in the TriNetX Network with HIV-CM and SGLT2i therapy were compared to a propensity matched control group of patients with HIV-CM without SGLT2i use. The primary endpoint was all-cause mortality. Secondary endpoints included all-cause hospitalization, acute heart failure (HF), acute myocardial infarction (MI), stroke, cardiac arrest, new atrial fibrillation, and ventricular tachycardia. Results: In the total of 2,606 included patients, SGLT2i therapy was associated with significant reduction in all-cause mortality (HR 0.475, 95%CI 0.337–0.671) and all-cause hospitalization (HR 0.725, 95%CI 0.646–0.814). No significant differences were observed rates of acute HF (HR 1.111, 95% CI 0.957–1.289), myocardial infarction (HR 0.828, 95% CI 0.555-1.235), stroke (HR 0.995, 95% CI 0.747–1.327), cardiac arrest (HR 0.564, 95% CI 0.308-1.036), atrial fibrillation (HR 0.954, 95% CI 0.798–1.140), or ventricular tachycardia (HR 1.225, 95% CI 0.898–1.672). Conclusions: SGLT2i use was associated with significant reductions in all-cause mortality and hospitalizations in patients with HIV-CM, but not cardiac specific outcomes.

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.

Background: We aimed to evaluate the outcomes of patients with confirmed and possible cardiac sarcoidosis who had an ICD implant and identify predictors of ventricular arrhythmias and mortality in this patient population. Methods: We performed a retrospective study patients with a diagnosis of cardiac sarcoidosis (CS) at Mayo Clinic and had an ICD implanted for primary or secondary prevention indication. Adult patients (≥18 years) with a diagnosis of possible or confirmed (biopsy-proven) CS with an ICD implanted between 1993 and 2022 were included. Primary outcomes included sustained ventricular arrhythmia (VT) resulting in a documented appropriate ICD shock and death from any cause. Secondary outcomes included ICD-related complications. Results: We identified 148 patients, in which 23 patients (15.5%) experienced VT events with a total of 160 treated episodes. 4 patients (2.7%) experienced inappropriate ICD shocks (11 episodes). During a median follow up of 3.1 years, 26 patients deceased, and the overall survival was 98% and 77% at 1 and 5 year. Older age, CAD, CKD, paced rhythm and QRS duration were associated with worse survival (Figure 1 – 4) . Device related complications were rare, except for the higher percentage of CHF in patients with VT after implant, however this was not statistically significant. Patients with ICD therapies were younger (53 vs 58 years, p=0.029), had higher LGE burden (26.9 vs 16.3%, p=0.01), and higher percentage of LV mass (26.9 vs 16.3, p=0.011). Multivariate logistic regression model which showed that patients with biopsy proven sarcoidosis had significantly higher odds of VT events (OR: 3.04, 95% CI: 1.02 to 9.08, p = 0.046). In patients with increased LV mass (every 10 g increase), the odds of developing VT increased by 1.49 (95% CI: 1.02 to 2.19, p = 0.041). LV mass and LGE percentage showed fair ability of predicting the outcome by ROC analysis. Youden’s index showed 26 for LV mass and 16% for LGE percent as the optimal cut-off points for predicting VT outcomes (Figure 5) . The sensitivity, specificity, positive predictive value, negative predictive value were 81.8%, 74.1%, 37.5%, 95.6% and 75.4% respectively for an LV mass of 26 grams and 81.8%, 63.8%, 30.0%, 94.9% and 66.7% respectively for an LGE percentage of 16%. Conclusion: LGE burden continues to be a major predictor for VT events in patients with CS. Myocardial tissue burden and electrical abnormalities from CS predict mortality than myocardial function loss.

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.

Background: A key determinant of prognosis in pulmonary hypertension (PH) is the right ventricle’s (RV) ability to adapt to increased pulmonary vascular resistance. Consequently, markers of RV-pulmonary artery (PA) coupling may improve prognostic prediction in PH. The ratio of tricuspid annular plane systolic excursion (TAPSE) to systolic PA pressure (sPAP) has been proposed as a surrogate for RV-PA coupling and a reliable prognostic marker, however, the existing data on the prognostic value of the ratio between RV longitudinal strain (RVLS) and sPAP as a surrogate for RV-PA coupling is scarce. Hypothesis: To evaluate the prognostic role of RVLS/RVSP in PH patients and to compare this novel marker with established markers of RV-PA coupling. Methods: This is a single-center study that included adult patients with PH classified as group I or IV, all of whom had undergone a transthoracic echocardiogram (TTE) within one year prior to the initiation of PH-specific treatment. Certified sonographers procured RV strain measurements using a specific software (Epsilon Imaging, Ann Arbor, MI). Receiver operating characteristic (ROC) analysis was used to determine the best cutoff for predicting all-cause mortality at one-year for RVLS/RVSP and TAPSE/RVSP. The association of RVLS/RVSP and TAPSE/RVSP with mortality at one year was assessed using the Kaplan-Meier analysis and multivariate Cox regression analysis (adjusted for REVEAL LITE 2.0 risk score). Results: A total of 160 patients were included with a median age of 67.2 (56.8, 73.7) years and 47 (29.2%) were male . ROC analysis revealed optimal cutoffs of 0.265 (AUC = 0.83) for RVLS/RVSP and 0.185 (AUC = 0.77) for TAPSE/RVSP to predict all-cause mortality at one year. One-year cumulative incidence of all-cause mortality was lower among patients with RVLS/RVSP ≥ 0.265 (0 % vs 13.7 %, p = 0.001) and patients with TAPSE/RVSP ≥ 0.185 (1.8 % vs 16.7 %, p = 0.001) (Figure 1) . In the multivariate analysis, RVLS/RVSP < 0.265 was associated with higher risk of mortality at one year (HR: 2.38, 95 % CI: 1.05 to 5.38, p = 0.036) while TAPSE/RVSP < 0.185 was not (HR: 2.01, 95 % CI: 0.93 to 4.31, p = 0.072). Conclusions: RVLS/ RVSP may be a valuable prognostic marker in PH patients and could outperform conventional TTE parameters as a surrogate for detecting RV-PA coupling.