Sorajja, Dan

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.

ABSTRACT Background Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) are primarily used to manage type 2 diabetes mellitus (T2DM) and heart failure (HF), but their impact on reducing stroke risk in patients with atrial fibrillation (AF) remains underexplored. We aimed to investigate the impact of SGLT2‐Is for stroke risk mitigation in patients with AF. Methods Using the TriNetX database, we performed a retrospective cohort study on patients ≥ 18 years with AF and on anticoagulation. These patients were then classified into two cohorts based on their use of SGLT2‐Is. To balance the baseline demographics, comorbidities, and medication use, propensity score matching (PSM) was used. The primary outcome was ischemic and hemorrhagic strokes, and the secondary outcomes were all‐cause mortality, all‐cause hospitalizations, need for AF cardioversion or antiarrhythmic drug initiation, and cardiac arrest. Adjusted odds ratio (aORs) and hazard ratios (HRs) were estimated for both the primary and secondary outcomes. Results A total of 152,778 patients with 76,389 patients were included in each cohort (SGLT2‐Is users, and non‐users) after PSM. The mean age of both SGLT2‐Is users and non‐users was 72.8 years. For the SGLT2‐Is users, the mean follow‐up period was 317 days, whereas the mean follow‐up period for the non‐users was 306 days. For the primary outcome, we found that SGLT2‐Is users had a lower risk of ischemic stroke (aOR: 0.889; 95% CI: 0.857–0.923) and hemorrhagic stroke (aOR: 0.682; 95% CI: 0.620–0.749) compared to non‐users. Regarding the secondary outcomes, SGLT2‐Is users also had lower risk for all‐cause mortality (aOR: 0.615; 95% CI: 0.595–0.636), all‐cause hospitalizations (aOR: 0.599; 95% CI: 0.587–0.611), need of AF cardioversion (aOR: 0.846; 95% CI: 0.813–0.881), antiarrhythmic drug initiation (aOR: 0.790; 95% CI: 0.766–0.815), and cardiac arrest (aOR: 0.643; 95% CI: 0.601–0.688). Conclusions SGLT2‐I use in patients with AF is associated with lower risks of stroke and other cardiovascular and non‐cardiovascular outcomes. Future prospective research is needed to validate these findings.

e19524 Background: Carfilzomib, a second-generation proteasome inhibitor, has emerged as one of the therapeutic agents in the treatment of relapsed or refractory multiple myeloma (MM). Despite its known cardiotoxicity, real-world data on its long-term cardiovascular outcomes remain limited. This study aimed to evaluate the real-world cardiovascular outcomes in patients with relapsed or refractory MM treated with carfilzomib. Methods: We utilized the TriNetX network to identify patients (≥18 years old) with relapsed or refractory MM between January 1, 2014, and January 1, 2019. We further categorized the patients into two groups: patients exposed to carfilzomib and patients not exposed to carfilzomib. Inclusion in the carfilzomib group required exposure to carfilzomib during the 5-year study period. Propensity score matching was performed to match these two groups based on comorbidities, medications, baseline hemoglobin A1c, low-density lipoprotein, and left ventricular ejection fraction to produce two comparable cohorts. The study outcomes were cardiovascular outcomes, including acute heart failure, acute myocardial infarction, cerebrovascular accident, acute venous thromboembolism, all-cause hospitalization, and all-cause mortality over the 5-year follow-up duration. Results: A total of 151,802 patients with relapsed or refractory MM were identified, including 6,386 patients (mean age 64.8 ± 10.6 years) who were exposed to carfilzomib and 145,416 patients (mean age 66.1 ± 12.7 years) who were not. After propensity score matching, there were 4,559 (65.3 ± 10.8 years of age, 44.7% female, 18.2% African American [AA]) patients who were exposed to carfilzomib and 4,559 patients who were not (65.2 ± 12.2 years of age, 45.1% female, 17.0% AA). Exposure to carfilzomib was associated with higher odds of acute heart failure (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.48-1.77, P < 0.001), acute myocardial infarction (aOR: 1.24; 95% CI: 1.03-1.48, P = 0.020), cerebrovascular accident (aOR: 1.97; 95% CI: 1.47-2.64, P < 0.001), acute venous thromboembolism (aOR: 1.79; 95% CI: 1.58-2.03, P < 0.001), all-cause hospitalizations (aOR: 1.91; 95% CI: 1.75-2.09, P < 0.001), and all-cause mortality (aOR: 1.97; 95% CI: 1.80-2.16, P < 0.001). Conclusions: Patients with relapsed or refractory MM who were exposed to carfilzomib had poorer cardiovascular outcomes compared to those who did not.

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.

Spontaneous type-1 Brugada patterns are associated with an elevated risk of major arrhythmic events, yet the relationship between varying degrees of pattern burden and the occurrence of a first major arrhythmic event remains unclear. This retrospective cohort study included 64 adult patients with a spontaneous type-1 Brugada pattern, who were identified at Mayo Clinic sites and followed for ≥12 months after the initial diagnosis. All patients underwent at least three 12-lead electrocardiograms (ECGs) within the first year. Individuals with prior major arrhythmic events were excluded. The percentage of ECGs showing a type-1 pattern was calculated and categorized as paroxysmal (<50%), persistent (50–99%), or permanent (100%). During a median follow-up of 92 months, seven patients (11%) experienced their first major arrhythmic event. Of these, one had paroxysmal, four had persistent, and two had permanent spontaneous type-1 Brugada patterns. Although statistical significance was not reached, the hazard ratios suggested a trend toward increased risk with persistent and permanent patterns compared to paroxysmal patterns. No sudden cardiac deaths occurred during follow-up. These findings suggest that a higher burden of spontaneous type-1 Brugada patterns may be associated with increased arrhythmic risk.

ABSTRACTBackgroundThe factors contributing to sustained ventricular arrhythmias (VAs) >30 days after left ventricular assist device (LVAD) implantation are not well‐established.ObjectivesThis study aimed to predict the factors associated with late sustained VAs after LVAD implantation and develop a predictive score to identify patients with an increased risk of late sustained VAs after the procedure.MethodsWe performed a retrospective cohort study on a training cohort of 623 patients and a validation cohort of 157 patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2000, to December 30, 2020. Late sustained VAs were defined as ventricular tachycardia (VT) and ventricular fibrillation (VF) occurring >30 days after the LVAD procedure. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed.ResultsA total of 780 patients were included in our study. Late sustained VAs occurred in 30% (n = 232) of the patients. The significant factors associated with late sustained VAs after LVAD were the history of VAs prior to LVAD (34.1% vs. 23.0%, p < 0.01), implantable cardiac defibrillator (ICD) (87.9% vs. 77.6%, p < 0.01) or cardiac resynchronization therapy (CRT) in situ (43.5% vs. 33.6%, p = 0.008), VT ablation prior to LVAD (5.2% vs. 1.8%, p = 0.010), use of amiodarone (49.1% vs. 38.7%, p = 0.007), use of mexiletine (15.5% vs. 5.7%, p < 0.01), and higher left ventricular end‐diastolic diameter (LVEDD) on echocardiography prior to LVAD implantation (71.4 vs. 68.7 mm, p = 0.002). During follow‐up, the patients who developed late sustained VAs after LVAD had lower survival than those who did not (HR = 1.96, 95% CI:156–2.4, p < 0.001). The average time from LVAD to orthotopic heart transplant was longer among late sustained VAs patients (23 vs. 14 months, p < 0.01). The “VIN” risk score was created to identify four risk groups: low (scores 0), intermediate (score 1), high (score 2), and very high (score 3). The rates of late VA's in the training cohort at 1 year were 9.5%, 14%, 18%, and 25% which was almost similar to the risk of late VA's at validation cohort 10%, 12%, 20%, and 63%, respectively.ConclusionsLate sustained VAs occurred in 30% of the patients who received LVAD and were associated with lower survival. The VIN risk score was developed and validated to stratify patients into low, intermediate, high, and very high risk of late sustained VAs.

Abstract Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although lipoprotein(a) [Lp(a)] is known to be a well-established risk factor for atherosclerotic cardiovascular disease, its role in the development of AF, independent of this association, remains unclear. Methods and results Adult patients from the three Mayo Clinic sites with a baseline Lp(a) and without AF history were included. Patients were categorized into two groups based on their Lp(a) levels: high Lp(a) (≥50 mg/dL) and low Lp(a) (&lt;50 mg/dL). Survival probabilities free from incident AF were compared between Lp(a) groups, during a follow-up period up to 15 years, using the Kaplan–Meier curve and the log-rank test. Multivariable Cox regression analysis was also conducted. A total of 75 376 patients were included (median age: 55 years, 59% males), with a median follow-up duration of 8.8 (inter-quartile range: 3.4, 14.8) years. Incident AF was detected in 5738 (7.6%) patients. Survival probability free from incident AF was significantly lower in patients with elevated Lp(a) (86%) compared with those with low Lp(a) (88%, log-rank P &lt; 0.001). Multivariable analysis adjusted for potential risk factors of AF showed a statistically significant association of elevated Lp(a) with an 11% increase in AF risk (adjusted hazard ratio: 1.11, 95% confidence interval: 1.05–1.18). Conclusion Our study suggests that elevated Lp(a) (≥50 mg/dL) is an independent risk factor for incident AF. Future prospective studies are warranted to validate our results and to test if reducing Lp(a) could mitigate the burden of AF.

Background: The optimal timing of pacemaker reimplantation following transvenous lead removal (TLR) of infected cardiac implantable electronic device (CIED) remains unclear. Objective: Our study aimed to assess the impact of timing to pacemaker reimplantation after TLR of infected CIED on hospital outcomes. Method: Using the Nationwide Readmissions Database, patients aged ≥18 years who underwent new pacemaker implantation with percutaneous approach following TLR of infected CIED from 2017 to 2020 were identified. The study population was stratified based on the timing of pacemaker reimplantation following TLR of infected CIED: early (<5 days) vs delayed (≥5 days). Weighted-propensity-score matched conditional multivariable logistic regressions were performed to determine the impact of the timing on various outcomes. Results: In our study, 469 (66.9%) patients received early device reimplantation, and 232 (33.1%) patients received delayed device reimplantation (≥5 days). Post-procedurally, patients in the delayed group had a higher risk of prolonged hospital stay (95% CI OR: 42.37 (6.36 – 282.11); p<0.01) and non-home discharge (95% CI OR: 2.00 (1.35 – 2.95), p<0.01). There was no significant difference between both groups in the early mortality, 30-day readmission, and procedural complications. Conclusion: Our study suggests that time-to-device reimplantation from TLR of infected CIED did not affect the overall short-term in-hospital outcomes. However, delayed device reimplantation was associated with a higher rate of prolonged hospital stay and non-home discharge.

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.