Farina, Juan M.

Abstract Aims Obesity is linked with worse outcomes in hypertrophic cardiomyopathy (HCM). While both bariatric surgery (BS) and GLP-1 receptor agonists (GLP-1RA) promote weight loss and may improve cardiometabolic risk, their comparative outcomes in HCM remain unclear. Methods and results Adults with HCM and body mass index (BMI) ≥ 30 kg/m were divided into two cohorts: (i) GLP-1 RA users who never had BS, and (ii) BS patients who never received GLP-1 RA. Propensity score matching (1:1) was performed to balance demographics, comorbidities, and medications. Outcomes over 24 months include all-cause mortality, acute heart failure (HF) hospitalization, arrhythmias, change in BMI, and cardiovascular symptoms. Hazard ratios with 95% confidence intervals were estimated using Cox models. Of 5002 patients, 955 were included in each matched cohort after matching (mean age 54 ± 13 years, 70% female, BMI 40.0 kg/m). GLP-1 RA was associated with a significantly lower observed rate of all-cause mortality compared with BS (2.0% vs. 4.4%; HR 0.46; 95% CI 0.27–0.80; P = 0.004) and HF hospitalization (8.7% vs. 14.0%; HR 0.60; 95% CI 0.46–0.79; P < 0.001). Similarly, GLP-1 RA use was associated with a lower incidence of composite cardiovascular outcomes (10.7% vs. 17.2%; HR 0.60; 95% CI 0.47–0.77; P < 0.001). Rates of arrhythmia and cardiovascular symptoms were comparable between the two groups. BMI reduction was greater after bariatric surgery (−4.0 vs. −2.6 kg/m; P < 0.001). Conclusion In obese patients with HCM, GLP-1 RA therapy was associated with lower all-cause mortality and fewer HF events compared with BS. Future studies are warranted to confirm our findings.

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 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.

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 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.

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.