Sorajja, Dan

ABSTRACT Background Atrial fibrillation (AF) is prevalent in cardiac amyloidosis (CA) and is associated with adverse clinical outcomes. Catheter ablation is increasingly used for rhythm control in this population, yet its clinical outcomes remain uncertain. We performed a systematic review and meta‐analysis to evaluate arrhythmia recurrence and clinical outcomes following catheter ablation compared with medical therapy in patients with CA. Methods We systematically searched MEDLINE, Embase, and Scopus from inception through December 2025 for studies evaluating catheter ablation of atrial arrhythmias in CA. Cohort studies reporting arrhythmia recurrence and/or clinical outcomes were included. The primary outcome was freedom from atrial arrhythmia (AA) following ablation. Secondary outcomes included all‐cause mortality, heart failure hospitalization, and stroke. Random‐effects models were used to pool event rates and odds ratios (ORs). Results Thirteen observational studies comprising 797 patients with CA and AF were included. The pooled rate of freedom from AA following catheter ablation was approximately 50% (95% CI 37%–63%; I 2 = 71.7%). The all‐cause mortality analysis included 4 observational studies comprising 616 patients. Catheter ablation was associated with lower odds of all‐cause mortality (OR 0.26, 95% CI 0.11–0.60; I 2 = 18.4%); however, this association should be interpreted with caution given the retrospective design and risk of bias. No statistically significant differences were observed for heart failure hospitalization or stroke. Conclusions In patients with CA, catheter ablation was associated with modest arrhythmia‐free survival and lower odds of all‐cause mortality. However, all contributing studies were observational cohorts. Randomized studies are needed to confirm these findings.

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: Transthyretin (TTR) cardiac amyloidosis is a progressive cardiomyopathy with high mortality; however, the role of implantable cardioverter-defibrillators (ICDs) in this population remains unclear. Methods: This retrospective cohort study included patients with confirmed TTR cardiac amyloidosis, with or without ICDs, from January 1, 2001, to December 31, 2024, across all three Mayo Clinic sites (Arizona, Florida, and Minnesota). Diagnosis was confirmed by endomyocardial biopsy or abnormal technetium pyrophosphate (PYP) scintigraphy. A 1:4 propensity score-matched cohort of non-ischemic cardiomyopathy (NICM) patients with ICDs served as a control group. The primary outcome was all-cause mortality, comparing transthyretin cardiac amyloidosis (TTR-CA) patients by ICD status and against matched NICM patients. Secondary analyses evaluated predictors of mortality, including the use of tafamidis and the indication for ICD (primary vs. secondary prevention). Kaplan–Meier and Cox regression analyses were used to assess predictors of survival and mortality. Results: A total of 463 patients with confirmed TTR cardiac amyloidosis were included. The median follow-up duration was 7.4 years (interquartile range (IQR): 5.3–9.2 years) for the non-ICD group and 6.8 years (IQR: 4.5–9.0 years) for the ICD group. The median age was 74.5 years (IQR: 68.0–80.0 years), and 92.9% of patients were male. Among them, 206 (44.5%) received ICDs and 257 (55.5%) did not. ICD recipients were younger (71.0 vs. 77.0 years; p = 0.001) and had higher rates of hypertension (62.6% vs. 45.6%; p = 0.001), chronic kidney disease (CKD) (62.6% vs. 44.4%; p = 0.001), and diabetes (30.1% vs. 21.8%; p = 0.043). Median left ventricular ejection fraction was lower in the ICD groups (43% vs. 54%; p = 0.007), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the ICD group (2259.0 pg/mL vs. 1503.0 pg/mL; p = 0.007). Among ICD recipients, 157 (76.2%) received the device for primary prevention, while 48 (23.3%) received the ICD for secondary prevention. Appropriate shocks were delivered in 22 patients (10.6%), primarily for ventricular tachycardia (n = 18) and ventricular fibrillation (n = 4). Inappropriate shocks occurred in six patients (3.0%), and 12 patients (5.8%) experienced device-related complications. Over 10 years of follow-up, ICD implantation did not confer a survival benefit for patients with TTR-CA compared to those without an ICD (p = 0.74). In contrast, a 1:4 propensity-matched NICM cohort with ICDs, which had a median follow-up of 7.1 years (IQR: 4.6–8.8 years), showed significantly improved survival than TTR-CA patients with ICDs (p = 0.034). Among the TTR-CA patients with ICDs, neither the use of tafamidis (p = 0.10) nor the ICD indication (primary vs. secondary prevention; p = 0.85) influenced mortality. In the Cox regression analysis, predictors of mortality in TTR-CA patients included older age (hazard ratio (HR) 1.048; p = 0.001), CKD (HR 1.637; p = 0.029), troponin T >50 ng/L (HR 1.594; p = 0.031), NT-proBNP >3000 pg/mL (HR 1.514; p = 0.050), and ejection fraction <40% (HR 1.935; p = 0.003). ICD implantation was not associated with improved survival (HR 0.932; p = 0.763). Conclusions: In conclusion, our data suggest that ICD therapy may not provide a significant overall survival benefit in older TTR-CA patients with impaired pump function; thus, prospective studies are warranted before any changes to clinical practice are considered. Key predictors of mortality included reduced ejection fraction and elevated cardiac biomarkers. Additional prospective studies are needed to clarify the role of ICDs in treatment strategies for patients with TTR-CA.

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of death among patients with kidney failure on dialysis. Social determinants of health may worsen this risk but are seldom incorporated into prognostic models. ICD-10 Z-codes provide standardized documentation of social determinants of health, yet their prognostic value in dialysis populations remains uncertain. This study examined whether Z-coded social determinants of health are associated with adverse cardiovascular outcomes and mortality among patients receiving dialysis for kidney failure. Methods A retrospective cohort study was conducted using the TriNetX Research Network (2010–2024), encompassing de-identified data from 103 institutions. Adults with kidney failure on chronic dialysis were stratified by the presence of ICD-10 Z-codes (Z55–Z65). Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory values. Primary outcomes were all-cause mortality and hospitalization; secondary outcomes included acute heart failure, myocardial infarction, stroke, cardiac arrest, bradyarrhythmias, and ventricular tachycardia. Results After matching, mean age was 62 years, and 42.4% were female in the Z-code cohort versus 41.2% in controls. Over one year, mortality occurred in 12.5% versus 10.9% (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.15–1.29) and all-cause hospitalizations in 57.3% versus 53.1% (HR, 1.22; 95% CI, 1.19–1.26). Cardiovascular complications were consistently higher in Z-coded patients, including heart failure (24.3% vs 20.5%; HR, 1.29), myocardial infarction (8.0% vs 7.1%; HR, 1.19), stroke (6.6% vs 6.2%; HR, 1.13), cardiac arrest (3.8% vs 3.1%; HR, 1.29), and bradyarrhythmias (6.9% vs 5.5%; HR, 1.33). Discussion Among patients with kidney failure, documented Z-coded social risk factors were associated with greater mortality and cardiovascular morbidity. Incorporating social determinants of health documentation into nephrology care may improve risk stratification and inform targeted interventions.

Abstract Aims We evaluated clinical outcomes with GLP-1 RA use post-TAVI in patients with T2D. GLP-1 receptor agonists (GLP1-RAs) lower cardiovascular risk in type 2 diabetes (T2D), but their impact in patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), remained unexplored. Methods and results We conducted a retrospective cohort study using the TriNetX network, including 25 184 adults (≥18 years) with T2D who underwent TAVI (2015–2023). Patients were stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for events from one-month post-TAVI until the most recent follow-up. PSM yielded 1101 patients per group, with a mean age of 73 years and 39% female. Mean follow-up duration was 2.2 ± 1.1 and 2.6 ± 1.8 years for GLP1-RA users and non-users, respectively. GLP1-RA use was also associated higher survival probability (HR: 0.708 [95% CI: 0.583–0.859]), and lower rates of all-cause hospitalization (HR: 0.790 [95% CI, 0.706–0.885]), major cardiovascular events (HR: 0.849 [95% CI: 0.749–0.963]), and acute heart failure exacerbation (HR: 0.785 [95% CI: 0.677–0.909]), acute kidney injury (HR: 0.843 [95% CI: 0.719–0.988]), and major kidney events (HR: 0.665 [95% CI: 0.510–0.866]). No differences were observed in acute myocardial infarction, cerebral infarction, or cardiac arrest. Conclusion In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiorenal outcomes. However, these findings are limited by the observational design, high comorbidity burden, lack of data on medication compliance, and specific cause of death. Prospective trials are warranted to confirm these benefits.

Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways. Beyond direct immunomodulators, GLP-1 receptor agonists and SGLT2 inhibitors provide both cardioprotective and anti-inflammatory benefits, reinforcing their expanding role post-ACS. Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic developments.

Abstract Background Inadvertent temporary transvenous pacing (TTVP) of left ventricle (LV) is rare and likely underreported, posing significant embolic risk. We present a case of TTVP with atypical trajectory identified on computed tomography (CT) imaging. Summary A 62-year-old male with metastatic renal cell carcinoma on chemotherapy and bifascicular block presented with symptomatic bradycardia and non–ST-elevation myocardial infarction (NSTEMI), raising concerns for complete heart block on ECG. Intermittent asystole occurred during TTVP placement with appropriate capture. Post-procedure, ECG showed ventricular-paced rhythm with pseudo-right bundle branch block, and chest X-ray suggested lead placement in right ventricle; however, suboptimal echocardiography limited lead visualization. Coronary angiography revealed non-obstructive coronary artery disease. Positron emission tomography–computed tomography (PET-CT), performed to evaluate immune checkpoint inhibitor myocarditis, incidentally noted TTVP wire entering right subclavian artery and traversing to LV. Patient underwent TTVP removal, endovascular repair, and pacemaker implantation; however, course was unfortunately complicated by embolic stroke and haemorrhagic conversion. Discussion Early detection and management of lead malposition remain critical to minimizing complications. Management strategies for inadvertent lead malposition (ILM) depend on duration of implantation, clinical presentation, and associated risks. This case highlights importance of recognizing this high-risk complication, preventive strategies, and evidence-based management. While existing data primarily focus on ILM in permanent devices, further research is needed to elucidate incidence, predictors, and outcomes of ILM in TTVP, particularly in resource-limited settings.

Cardiac cachexia (CC) is a severe complication of advanced heart failure (HF), characterized by involuntary weight loss and muscle wasting, leading to poor outcomes and higher mortality. Despite its severity, CC remains under-recognized and undertreated, lacking targeted therapies specifically addressing its pathophysiology. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), though beneficial in reducing cardiovascular risk in patients with HF, may exacerbate muscle wasting in cachectic patients, necessitating further investigation. Non-pharmacological strategies, including tailored nutritional support and exercise programs, have shown positive effects on body composition and quality of life in patients with CC. However, there remains a gap in recommendations tailored to preventive strategies and pharmacologic therapies for patients with CC and concomitant GLP-1RA use. This review highlights the multifactorial mechanisms underlying CC and current and emerging therapeutic approaches for mitigating HF-related sarcopenia while on GLP-1RAs.