BACKGROUND:Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have demonstrated survival benefits and cardioprotective effects in diabetic and heart failure (HF) patients. However, the association of GLP-1RAs use with mortality and morbidity in heart transplant (HT) recipients has not been previously investigated. METHODS:All adult patients who underwent HT at three Mayo Clinic sites and survived at least one month after the procedure were assessed. GLP-1RAs use was extracted retrospectively from the electronic medical records (EMR) after the HT. All-cause mortality and hospitalization due to graft dysfunction, graft rejection, vasculopathy, de novo DM, and dialysis were collected and compared between patients exposed and non-exposed to GLP-1RA using Kaplan-Meier curves, cumulative incidence functions, and multivariate Cox regression analyses incorporating GLP-1RA exposure as a time varying covariate. RESULTS:A total of 1914 patients were included with a median age of 56.3 (46.1, 62.8) years and 71.2% were male. The median follow up was 5.5 (2.2,10.2) years and 285 (14.9%) used GLP-1RAs following HT. In the multivariable time-dependent Cox analysis, GLP-1RA therapy was associated with lower risk of all-cause mortality (HR: 0.33, 95% CI: 0.12 to 0.90; p = 0.031), but not with hospitalization due to graft dysfunction (HR: 0.95, 95% CI: 0.45 to 2.01; p = 0.900) or other outcomes through 5-year follow-up. CONCLUSIONS:Therapy with GLP-1RAs was associated with a lower risk of all-cause mortality in HT recipients. While the mechanisms of these associations need further investigations, these findings, suggest a potential therapeutic role to improve survival after HT.

Cirrhosis induces a hyperdynamic circulatory state with portal hypertension, leading to chronic right ventricular volume overload and tricuspid annular dilation, often resulting in functional tricuspid regurgitation (TR). Severe TR exacerbates hepatic congestion and significantly increases perioperative risk during liver transplantation. We present a 52-year-old woman with decompensated cirrhosis secondary to alcohol use who was initially deemed ineligible for liver transplantation due to severe TR. Despite aggressive medical optimization, her TR persisted, and surgical repair was contraindicated due to prohibitive operative risk. The patient subsequently underwent successful transcatheter tricuspid valve edge-to-edge repair, reducing TR from severe to mild. This intervention enabled her to qualify for successful simultaneous liver-kidney transplantation with favorable postoperative graft function. This case highlights the potential role of transcatheter tricuspid valve edge-to-edge repair as a bridge to transplantation in patients with decompensated cirrhosis and severe TR when conventional surgical approaches have an excessive risk. Multidisciplinary collaboration is critical, and further studies are warranted to define outcomes and establish selection criteria in this high-risk population.

Background:Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied. Methods:This retrospective cohort study used TriNetX data (January 2010-December 2023) to compare outcomes in liver transplant recipients prescribed GLP1RAs (semaglutide, dulaglutide, liraglutide) within 1-mo posttransplant (n = 546) versus nonusers (n = 37 153). Propensity score matching (1:1) balanced demographics, comorbidities, and medications (n = 541 per group). Outcomes included mortality, hospitalizations, cardiovascular/renal/respiratory events, and graft outcomes. Results:Over a mean follow-up 838.5 d (SD 291.9) in the GLP1RA cohort and 884.3 d (SD 313.7) in the non-GLP1RA group, GLP1RA use was associated with a 43% lower all-cause mortality (7.0% versus 12.9%; hazard ratio [HR], 0.566; 95% confidence interval [CI], 0.381-0.841) and 39% fewer hospitalizations (60.4% versus 74.5%; HR, 0.613; 95% CI, 0.530-0.710). Acute heart failure (HR, 0.386; 95% CI, 0.285-0.524), renal failure/dialysis (HR, 0.489; 95% CI, 0.413-0.579), and respiratory failure (HR, 0.484; 95% CI, 354-0.662) risks were significantly reduced. No differences were observed in graft failure/rejection, myocardial infarction, stroke, atrial fibrillation/flutter, ventricular tachycardia, or ischemic optic neuropathy. Conclusions:Early GLP1RA initiation in liver transplant recipients was associated with reduced mortality, hospitalizations, respiratory, and cardiorenal complications without compromising graft safety. These findings support GLP1RAs as a promising adjunct therapy, warranting prospective trials to confirm benefits in this high-risk 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.

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.

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. To evaluate and compare clinical efficacy and safety outcomes of DOACs versus warfarin in patients with ATTR-CA and AF. 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. 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. 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.

Introduction:Pulmonary hypertension (PHTN) in patients with kidney failure is known to be associated with increased morbidity and mortality. Despite this, there is a relative paucity of large cohort data regarding its clinical impact following kidney transplantation (KTx). Therefore, this study sought to directly evaluate the prognostic implications of pretransplant PHTN in one of the largest kidney transplant cohorts to date. Methods:This retrospective observational cohort analysis reviewed all consecutive kidney transplant recipients at three tertiary transplant centers in the United States between January 1, 2011 and September 30, 2021. Pretransplant PHTN was defined as right ventricular systolic pressure (RVSP) ≥ 35 mm Hg on transthoracic echocardiography (TTE). Clinical outcomes were compared between patients with and without pretransplant PHTN, including mortality and allograft failure (overall and censored by mortality). Results:A total of 5322 KTx recipients were included; mean age 55.2 ± 13.7 years, 58.8% male. Of these patients, 1726 (32.4%) had pretransplant PHTN. PHTN was independently associated with significantly poorer outcomes: mortality (adjusted hazard ratio [aHR]: 1.24, 95% confidence interval [CI]: 1.06-1.45, P = 0.007), overall allograft failure (aHR 1.24, 95% CI: 1.09-1.42, P = 0.002), and death-censored allograft loss (aHR: 1.25, 95% CI: 1.01-1.56, P = 0.044). Risk of mortality and overall allograft failure also appeared to be incrementally higher with increasing pulmonary pressures. Conclusion:Pretransplant PHTN classified by echocardiographic RVSP was independently and incrementally associated with an increased risk of mortality and allograft failure post-KTx. In pretransplant work up, this may allow for identification of a high-risk cohort that could benefit from further evaluation, early intervention, and closer surveillance in the posttransplant period.

OBJECTIVE:To understand clinical and health economic outcomes in patients receiving standard-of-care (SOC), out-of-hospital management for recently diagnosed heart failure (HF) in the US. STUDY DESIGN:Systematic literature review with a subsequent pooled rates analysis. METHODS:Researchers reviewed randomized controlled trials (RCTs) indexed in PubMed and EMBASE between 2008 and 2023. RCTs were selected as the data sources because of the standardized reporting on outcomes and prospective data. Studies included in the analysis reported on US patients recently diagnosed with HF who underwent watchful waiting after discharge. The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with details reported in the PROSPERO study protocol (No. CRD42023410084). The pooled estimates of all-cause and HF-specific hospital readmissions, length of hospital stay, emergency department visits, and mortality at 3, 6, and 12 months were calculated using R software's meta and metafor packages. RESULTS:There were 31 studies that met the inclusion criteria and reported data for 6916 patients with HF receiving SOC. The proportions of patients with a readmission and an emergency department visit at 3 months were 32.55% (95% CI, 24.03%-41.63%) and 13.83% (95% CI, 8.21%-20.49%), respectively. Mortality over the same period was 3.46%. Quality-of-life and cost data were heterogeneous and infrequently reported, preventing pooled analyses of these data. Length of stay had a pooled value of 7.12 days (95% CI, 5.78-8.46). CONCLUSION:HF with SOC monitoring is associated with substantial health care burden. Improvements in SOC monitoring, potentially through remote monitoring and management, could be beneficial to patients, clinicians, and payers.

BACKGROUND:Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease associated with high morbidity and mortality. Tafamidis is the only US Food and Drug Administration-approved disease-modifying therapy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have shown promise in heart failure and may offer additive benefit when combined with tafamidis, although this remains unclear. METHODS:Using the TriNetX global research network, we identified adults with ATTR-CM treated with tafamidis between 2019 and 2022. Patients were stratified by concomitant use of SGLT2-Is (empagliflozin, dapagliflozin, or canagliflozin). Primary outcome was all-cause mortality; secondary outcomes included all-cause hospitalizations, acute myocardial infarction (AMI), stroke, heart failure hospitalizations, arrhythmias, and end-stage renal disease at 1- and 3-year follow-up. RESULTS:After matching, 409 patients remained in each cohort. Combination therapy with SGLT2-Is and tafamidis was associated with significantly lower all-cause hospitalizations (1-year: OR 0.67, p = 0.005; 3-year: OR 0.67, p = 0.006) and AMI (1-year: OR 0.44, p = 0.001; 3-year: OR 0.56, p = 0.004). No significant mortality reduction was observed at either time point. No significant differences were observed for any of the other secondary outcomes. CONCLUSIONS:In patients with ATTR-CM treated with tafamidis, adjunctive SGLT2-I use was associated with lower rates of hospitalization and AMI, without a significant mortality benefit. These findings support further prospective evaluation of combination therapy.

Lipoprotein(a) [Lp(a)] has been established as an independent risk factor for cardiovascular diseases. However, its role in cardiac allograft vasculopathy (CAV) development remains controversial. In a retrospective cohort study of 385 patients who underwent heart transplant between 2001 and 2023, Lp(a) concentrations were compared between patients with and without clinically significant CAV (grade 01 vs 2-3). Preoperative Lp(a) concentrations were not significantly different between patients with and without CAV (14.0vs 12.0 mg/dL, P = . 42). High ( >= 50 mg/dL) Lp(a) values were not associated with CAV development on univariable or multivariable analysis (hazard ratio [HR] 1.009, 95% CI: 0.47-2.14, P = . 9). A history of graft rejection was the only independent factor associated with CAV (HR 2.88, 95 % CI: 1.50-5.52, P = . 001). Elevated Lp(a) levels were not associated with increased risk of CAV. The lack of a significant association between traditional risk factors and CAV underscores that CAV is not purely an atherosclerotic process and different pathophysiological mechanisms are involved. (c) 2024 National Lipid Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:BK polyomavirus DNAemia is common in solitary kidney transplants (KTs), with the risk of developing BK DNAemia-associated nephropathy, but data is limited in simultaneous heart-KTs. Our aim was to assess the prevalence and outcomes of BK DNAemia after simultaneous heart-KT. METHODS:Retrospective study between January 1, 2005, and June 30, 2022, analyzing the prevalence of BK DNAemia and BK DNAemia-associated nephropathy rates in simultaneous heart-KT recipients between BK DNAemia positive and BK DNAemia negative groups. Secondary outcomes included heart and kidney allograft function, kidney allograft survival, rejection rates, and patient survival. RESULTS:Thirty-eight percent developed BK DNAemia, while 47% of patients with BK DNAemia developed BK DNAemia-associated nephropathy. The median time to first detection of BK DNAemia was 86 days (IQR: 50-118 days) and resolution was 216 days (IQR: 106-366 days). The BK DNAemia positive group had significantly higher kidney rejection rates (47% vs 25%; p = 0.01). There was no significant difference in patient survival (p = 0.7) or allograft function of either allograft between the two groups. Immunosuppression was reduced more frequently in the BK DNAemia positive group (84% vs 46%; p < 0.001). There was an increased risk of subsequent kidney rejection in patients who developed BK DNAemia (p = 0.024). CONCLUSION:BK DNAemia and BK DNAemia-associated nephropathy are common in simultaneous heart-kidney recipients, leading to increased kidney rejection rates without affecting overall patient survival or allograft kidney and heart function.

Cardiac amyloidosis (CA) is an underdiagnosed form of infiltrative cardiomyopathy caused by abnormal amyloid fibrils deposited extracellularly in the myocardium and cardiac structures. There can be high variability in its clinical manifestations, and diagnosing CA requires expertise and often thorough evaluation; as such, the diagnosis of CA can be challenging and is often delayed. The application of artificial intelligence (AI) to different diagnostic modalities is rapidly expanding and transforming cardiovascular medicine. Advanced AI methods such as deep-learning convolutional neural networks (CNNs) may enhance the diagnostic process for CA by identifying patients at higher risk and potentially expediting the diagnosis of CA. In this review, we summarize the current state of AI applications to different diagnostic modalities used for the evaluation of CA, including their diagnostic and prognostic potential, and current challenges and limitations.

Background: New-onset atrial fibrillation (AF) is common among kidney transplant (KTx) recipients and is associated with reduced patient survival. Predictors of AF after KTx are not well understood, although AF can be associated with traditional and non-traditional risk factors. While artificial intelligence-enabled electrocardiography (AI-ECG) has shown promise in predicting incident AF, its predictive and prognostic implications in the KTx population have not yet been evaluated. Hypothesis: AI-ECG can predict new-onset AF and carries prognostic implications in patients undergoing KTx. Aims: To evaluate the clinical implications of applying AI-ECG to the preoperative ECGs of recipients of a KTx. Methods: Patients without a history of AF who underwent KTx at three referral centers between 2011 and 2021, with at least one preoperative ECG, were included in this retrospective study. Preoperative ECGs were analyzed using a previously developed AI-ECG algorithm to estimate the probabilities of new-onset AF. Based on these probabilities, patients were categorized into two groups: high and low probability of incident AF. The optimal cut-off value for the AI-ECG tool was determined using ROC analysis. The incidence of new-onset AF and mortality at 5 years post KTx were compared between these two groups using univariate and multivariate Cox regression analyses. Results: In total, 6246 patients were included (mean age 52.9 ±14.3 years, 58.7% males). A pre-transplant AI-ECG probability of AF >10% was identified as the most accurate cutoff point to distinguish between patients at low risk and high risk of incident AF (ROC = 0.72). The study found that a preoperative AI-ECG high risk of AF demonstrated not only a strong association with new-onset AF (HR 2.54, 95%CI 2.02-3.19, p<0.001 on multivariable analysis, Figure 1A ) but was also associated with an increased risk of mortality both on univariate (HR 2.73, 95%CI 2.34-3.18, p<0.001) and multivariate (HR 1.57, 95%CI 1.29-1.91, p<0.001 ) analysis at 5-year follow-up ( Figure 1B ). Conclusion: The application of AI-ECG to a single widely available test may help assess the risk of new-onset AF and mortality in patients undergoing KTx. Accurate risk stratification may identify a high-risk subgroup of transplant recipients who can benefit from closer AF monitoring, risk factor modification, and early management.