Citations

Background: Indications for TAVR explant have been established, although limited data exist regarding pre-TAVR baseline characteristics that predict eventual explantation. Methods: The TriNetX network, a database comprising medical records from over 105 institutions, was used. Two cohorts were created: those who underwent TAVR without explant and those requiring subsequent TAVR explant and SAVR. Predictors of explantation were analyzed by multivariate models. Results: Among the 63,377 patients undergoing TAVR, 273 (0.4%) required explantation. Patients in the explant group were younger (69.1 ± 11.3 vs. 78.1 ± 8.8 years; p < 0.001), more likely to have a thoracic aortic aneurysm (TAA) (10.6% vs. 4.7%; p < 0.001) and had higher LDL levels (88.2 ± 41.3 vs. 80.7 ± 34.6 mg/dL; p = 0.011). They also had increased post-TAVR rates of acute kidney injury (9.2% vs. 5.2%; p = 0.004) and paravalvular leak (5.9% vs. 0.9%; p < 0.001). Age at TAVR (HR 1.04; CI 1.03–1.06), baseline TAA (HR 1.69; CI 1.09–2.63), history of infective endocarditis (HR 1.92; CI 1.10–3.35), and higher LDL (HR 1.02; 95% CI 1.00–1.03) were independent predictors for explantation. Conclusions: Younger age at TAVR, TAA, history of endocarditis, and elevated baseline LDL were notable predictors of explantation. These findings highlight the necessity of pre-procedural assessment and follow-up in high-risk patients to optimize TAVR durability.

ABSTRACT This international, multidisciplinary consensus report represents the first effort to systematically define and characterize fatty pancreas. A key outcome of this endeavor was the recommendation to adopt “fatty pancreas” as the standardized and inclusive term to describe all forms of fat accumulation in the pancreas. This terminological consensus provides a critical foundation for unified reporting and clinical communication. Another major contribution of the report is the consensus on diagnostic imaging findings, which was based on radiological and endoscopic modalities. The proposed criteria aim to enhance consistency in clinical assessment and support the development of standardized research protocols. In addition to establishing terminology and diagnostic frameworks, the report also synthesizes current knowledge across a wide range of relevant domains. These include the etiology and epidemiology of fatty pancreas, as well as its associations with alcohol consumption, smoking, acute and chronic pancreatitis, pancreatic exocrine insufficiency, type 2 diabetes mellitus, and surgical outcomes. The potential links between fatty pancreas and neoplastic conditions such as intraductal papillary mucinous neoplasms and pancreatic cancer are also addressed, alongside the current understanding of its metabolic implications (beta‐cell function and glucose homeostasis) and treatment strategies. Throughout the consensus process, a consistent theme emerged: the limited availability of high‐quality, prospective clinical data. Therefore, many of the recommendations in this report are based on expert consensus rather than strong empirical evidence. As such, the statements require rigorous prospective validation before they can be adopted into routine clinical practice. This underscores a critical need for further research, particularly studies aimed at clarifying causal relationships, validating diagnostic tools, and determining the clinical relevance of fatty pancreas across diverse patient populations. This report serves as both a summary of our current understanding and a roadmap for future investigations, aiming to close existing knowledge gaps and guide evidence‐based clinical practice in this emerging field.

Abstract Background Loeys-Dietz Syndrome (LDS) is a rare connective tissue disorder characterized by mutations indifferent genes including TGFRB2, TGFBR1, TGFB2, TGFB3, and SMAD3, which significantly increase the risk of vascular abnormalities, including aneurysms and dissections. These vascular events can involve various arterial territories, although the thoracic aorta is of most concern. The current literature is limited on characterizing the aortic and extra-aortic vascular manifestation on larger cohorts of patients. Purpose This study aims at analyzing the rates of aneurysms and dissections across different vascular territories inpatients with LDS. Methods A retrospective analysis was conducted on a cohort of individuals diagnosed with LDS at our institution. Medical records were reviewed for imaging findings, including CT scans, MRIs, and ultrasounds, to identify the presence of aneurysms and dissections. Vascular territories involved included the aortic arch (ascending, and descending aorta), coronary, cerebral, carotid, vertebral, renal, splanchnic, and peripheral arteries. Results A total of 94 patients with LDS were included. 76 patients (81%) had an ascending aortic aneurysm, and 21 patients (22.5%) had an abdominal aortic aneurysm. 49 patients (52%) had aneurysms in other vascular territories, with some patients having multiple aneurysms in different regions. These included 9 patients (9.5%) with carotid, 3 patients (3.2%) with vertebral, 5 patients (5.3%) with splenic, 11 patients (11.7%) with mesenteric, 2 patients (2.1%) with renal, 15 patients (15.9%) with iliac/femoral, 6 patients (6.4%) with subclavian, 23 patients (24.5%) with cerebral, and 10 patients (10.6%) with coronary aneurysms. For aortic dissections, 13 patients (14%) had type A and 9 patients (9.5%) had type B dissections. Additionally, 20 patients had dissections in other vascular territories, with some patients experiencing dissections in multiple regions. These included 8 patients (8.5%) with carotid, 8 patients (8.5%) with vertebral, 1 patient (1.1%) with renal, 3 patients (3.2%) with iliac, 2 patients (2.1%) with coronary, and 3 patients (3.2%) with innominate artery dissections. Conclusion Aortic involvement is the most common in patients with LDS; however, these patients are also at an increased risk of developing aneurysms and dissections in various vascular territories. This highlights the importance of screening and close follow-up in these patients, potentially through whole-body imaging to identify such abnormalities. Further research is needed to identify patients at higher risk for aneurysms and dissections compared to others.

Abstract Background Treatment with immune-checkpoint inhibitors (ICI) may be associated with adverse cardiac events. Troponin elevation is part of the diagnostic criteria for ICI related myocarditis (ICIrM) and myocardial infarction (MI), however there is limited data for causes of troponin elevation independent of MI and ICIrM and their clinical outcomes with ICI therapy. Purpose To assess the diagnostic and prognostic value of high-sensitivity troponin T (hs-TnT) in patients treated with ICI based on different etiologies and association with cardiac events. Methods All patients treated with ICI who had hs-TnT measured at a multi-center institution from 2011 to 2022 were included. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death and MACE (MI, stroke, heart failure [HF]), and cause of hs-TnT elevation. Risk of cardiac events and mortality were compared for the different etiologies of hs-TnT elevation. Results Of 5,423 patients treated with ICI, 1669 had post-ICI hs-TnT measurement. Mean age was 68.7±11.3 years, 58.3% were male, with follow-up through one year from ICI first administration. Elevated hs-TnT was seen in 1136 patients, with the different causes for elevation depicted in Figure 1, panel A. ICIrM patients exhibited the highest median hs-TnT value of 364 ng/L (IQR 1096), followed by a median of 98 ng/L for MI/Type 2 ischemia, 61 ng/L for infection/sepsis, 51 ng/L for pulmonary embolus, 50 ng/L for HF and 27 ng/L for indeterminate causes, Figure 1, panel B. Additionally, median time from first ICI dose to hs-TnT elevation according to each of the diagnoses are depicted in Figure 1, panel C, with ICIrM showing the shortest median time of 44 days (IQR 74). Hs-TnT elevation in patients with ICIrM had the highest risk for cardiac death (HR 52.7, 95% CI 11.7-238.0, p&lt;0.001), followed by hs-TnT elevation due to HF (HR 15.9, 95% CI 2.9-87.0, p=0.001), MI/type 2 ischemia (HR 11.6, 95% CI 2.4-56.1, p=0.002), and infection/sepsis (HR 5.7, 95% CI 1.0-31.0, p=0.045) compared to those with no hs-TnT elevation, Figure 2, panel A. Similarly, patients with ICIrM had highest risk for MACE (HR 8.2, 95% CI 4.4-15.3, p&lt;0.001), followed by increased hs-TnT due to MI/type 2 ischemia (HR 8.1, 95% CI 5.0-13.1, p&lt;0.001), HF (HR 7.6, 95% CI 4.2-13.7, p&lt;0.001), pulmonary embolism (HR 5.1, 95% CI 2.5-10.8, p&lt;0.001), infection/sepsis (HR 4.1, 95% CI 2.4-7.0, p&lt;0.001), and indeterminate cause (HR 2.4, 95% CI 1.5-3.8, p&lt;0.001), Figure 2, panel B. Conclusions Hs-TnT measurements have prognostic value for cardiac events in cancer patients receiving ICI therapy, including in those without ICIrM. Patients with ICIrM demonstrated the highest median hs-TnT levels and the poorest outcomes, with a graded response observed; the worst prognosis was seen in patients with hs-TnT elevation due to ICIrM, followed by other causes, and those without hs-TnT elevation had the best prognosis.Figure 1 Figure 2

Abstract Background/Introduction Acute coronary syndrome (ACS) is common among elderly patients and is associated with a high risk of complications. Managing ACS, particularly dual antiplatelet therapy (DAPT), poses challenges due to the increased risk of recurrent hemorrhagic and ischemic events in this population. Purpose This study evaluated cardiovascular outcomes in patients ≥75 years that were initiated on DAPT with aspirin (ASA) plus either ticagrelor or clopidogrel following an acute myocardial infarction (AMI). Methods We used the TriNetX repository to identify adult patients (≥75 years) diagnosed with AMI between January 1, 2011, and December 31, 2021, who subsequently initiated DAPT and were not on anticoagulation. Patients were stratified into two cohorts: ASA + ticagrelor and ASA + clopidogrel. Outcomes assessed included major bleeding, repeat coronary intervention, all-cause mortality, all-cause hospitalizations, stroke, new-onset atrial fibrillation, and pacemaker implantation. Follow-up time was restricted to one year. A 1:1 propensity score matching algorithm was applied using the greedy nearest-neighbor method with a caliper of 0.1 pooled standard deviations to ensure balance (i.e., comorbidities, medications, laboratory values) between the two cohorts. Logistic regression models were used to calculate adjusted odds ratios (aOR), and Cox proportional hazards models estimated hazard ratios (HR). Results Before propensity score matching (PSM), 19,859 patients were in the ASA + ticagrelor cohort, and 47,032 were in the ASA + clopidogrel cohort. Post-PSM, 19,746 patients remained in each cohort, with a mean age of 82.2 years and a mean follow-up duration of 298.77 days for the ASA + ticagrelor cohort and 297.59 days for the ASA + clopidogrel cohort. The ASA + ticagrelor cohort had a higher incidence of major bleeding (aOR 1.19 [95% CI, 1.08–1.31]) and pacemaker implantation (aOR 1.14 [95% CI, 1.02–1.29]) compared to the ASA + clopidogrel cohort. Event-free survival analysis showed lower survival rates for major bleeding (HR 1.18 [95% CI, 1.07–1.30]) and pacemaker implantation (HR 1.14 [95% CI, 1.01–1.28]). No significant differences were observed between cohorts in repeat coronary interventions (aOR 0.95 [95% CI, 0.88–1.03]), atrial fibrillation (aOR 1.03 [95% CI, 0.97–1.08]), all-cause mortality (aOR 1.03 [95% CI, 0.96–1.12]), all-cause hospitalization (aOR 1.01 [95% CI, 0.97–1.05]), or stroke (aOR 0.95 [95% CI, 0.86–1.04]). Conclusions In elderly patients, DAPT with ASA + ticagrelor was associated with higher rates of major bleeding and need for pacemaker compared to ASA + clopidogrel. Given the similar risks of recurrent coronary intervention and mortality between the two regimens, these findings highlight the need for careful consideration when selecting ticagrelor over clopidogrel in this population.

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 Introduction/Background Transthyretin amyloidosis (ATTR) is a debilitating disease that leads to progressive cardiac dysfunction. Tafamidis is the gold standard therapy for ATTR cardiomyopathy. In recent observational studies, sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have demonstrated cardiovascular benefits in ATTR cardiomyopathy, but their role in ATTR cardiomyopathy as combination therapy with tafamidis remains unclear. Purpose To investigate the impact of combination therapy with tafamidis and SGLT2-Is versus just tafamidis in patients with known ATTR cardiomyopathy. Methods This retrospective cohort study utilized data from the TriNetX multinational database. Patients diagnosed with ATTR cardiomyopathy who received tafamidis were identified and stratified into two cohorts based on SGLT2-I use. Outcomes were assessed over three years, including all-cause mortality, all-cause hospitalizations, acute myocardial infarction (AMI), acute heart failure (HF) hospitalizations, ischemic stroke, atrial fibrillation/flutter, end-stage renal disease (ESRD) or requirement for renal replacement therapy, and ventricular tachycardia. Propensity score matching was used to balance both cohorts based on clinical comorbidities, medication use, and laboratory data. Adjusted odds ratios (OR) were calculated by logistic regression models. Results After propensity score matching, 409 patients were included in each cohort with a follow-up duration of 722 days (SD 320.87) for the SGLT2-I cohort and and 755.90 days (SD 363.26) for the non-SGLT2-I cohort. SGLT2-Is were associated with significantly lower rates of all-cause hospitalizations (41.1% vs. 50.9%; OR 0.67 [p = 0.005]) and AMI (6.6% vs. 13.9%, OR 0.44 [p = 0.001]), which persisted by three years (all-cause hospitalizations: 52.1% vs. 61.4%, OR 0.67 [p = 0.006] and myocardial infarction: 11.2% vs. 18.3%, OR 0.56 [p = 0.004]). No significant differences among the two cohorts were observed for all-cause mortality, acute HF hospitalizations, ischemic stroke, atrial fibrillation/flutter, ventricular tachycardia, or ESRD/need for renal replacement therapy. Conclusions SGLT2-Is, in combination with tafamidis, are associated with decreased all-cause hospitalizations and AMI in ATTR cardiomyopathy. While a mortality benefit was not demonstrated, these results depict the magnitude of clinical benefit derived from combination therapy with tafamidis and SGLT2-Is as opposed to prior observational studies which investigated SGLT2-I single therapy

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.

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.