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ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

ABSTRACT Cavotricuspid isthmus ablation (CTI) is a first‐line therapy in patients with typical atrial flutter. With the advent of pulsed field (PF) as a new energy source, we sought to evaluate the use of PF for CTI ablation. A systematic literature search was conducted on the use of PF for CTI‐flutter up to December 2024. A meta‐analysis was performed for studies reporting pooled data, while individual case reports were reviewed and summarized. The mean number of PF applications, acute success rate, and prevalence of coronary vasospasm were evaluated. Eleven studies with pooled data from 155 patients were included. All patients had an acute block of the CTI. The mean number of PFA applications was 7.78 (95% CI 6.53–9.48). The incidence of ST‐elevation was 0.04% (95% CI 0–2.23%). Subclinical vasospasm was documented in 45% (95% CI 32%–59%) of patients who underwent periprocedural coronary angiography. Prophylactic use of nitrates showed a trend toward reducing the incidence of subclinical vasospasm (RR 0.24, 95% CI 0.06–1.06, p = 0.059). Twelve cases with patient‐level data were included; six reported complications, including ST elevation and conduction disturbances. PFA for CTI flutter demonstrates high acute success; however, evidence regarding the durability of the block is limited. Clinical vasospasm with ST segment elevation is uncommon but can lead to life‐threatening complications. The incidence of subclinical vasospasm is high, and nitrates tend toward reducing this phenomenon. To date, the role of PFA for this condition appears to be limited.

Background: Cavotricuspid isthmus ablation (CTI) is a first line therapy in patients with typical atrial flutter. With the advent of Pulsed Field (PF) as a new energy source, we sought to evaluate the use of PF for CTI ablation. A systematic literature search was conducted on the use of PF for CTI-flutter up to December 2024. A meta-analysis was performed for studies reporting pooled data, while a patient-level summary was done for reports with available individual data. The mean number of PF applications, acute success rate, and prevalence of coronary vasospasm were evaluated. Results: Eleven studies with pooled data from 155 patients were included. All patients had an acute block of the CTI. The mean number of PFA applications was 7.78 (95% CI 6.53–9.48). The incidence of ST-elevation was 0.04% (95% CI 0-2.23%). Subclinical vasospasm was documented in 45% (95% CI 32%–59%) of patients who underwent periprocedural coronary angiography. Prophylactic use of nitrates showed a trend toward reducing the incidence of subclinical vasospasm (RR 0.24, 95% CI 0.06–1.06, p=0.059). Twelve cases with patient-level data were included; six reported complications, including ST elevation and conduction disturbances. Conclusion: PFA for CTI flutter demonstrates high acute success; however, evidence regarding the durability of the block is limited. Clinical vasospasm with ST segment elevation is uncommon but can lead to life-threatening complications. The incidence of subclinical vasospasm is high, and nitrates trend toward reducing this phenomenon. To date, the role of PFA for this condition appears to be limited.

Abstract The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023. The symposium featured presentations on a wide array of topics, including studies on slow-aging animals, cellular senescence and senotherapeutics, the role of the immune system in aging, metabolic changes in aging, neuronal health in aging, and biomarkers for measuring the aging process. Speakers shared findings from studies involving a variety of animals, ranging from commonly used species such as mice, rats, worms, yeast, and fruit flies, to less-common ones like naked mole-rats, painted turtles, and rotifers. MAC continues to emphasize the importance of supporting emerging researchers and fostering a collaborative environment, positioning itself as a leader in aging research. This symposium not only showcased the current state of aging biology research but also highlighted the consortium’s role in training the next generation of scientists dedicated to improving the healthspan and well-being of the aging population.

Abstract Aims Pericardiocentesis is usually completed under fluoroscopy. The electroanatomic mapping (EAM) system allows visualizing puncture needle tip (NT) while displaying the electrogram recorded from NT, making it possible to obtain epicardial access (EA) independent of fluoroscopy. This study was designed to establish and validate a technique by which EA is obtained under guidance of three-dimensional (3D) EAM combined with NT electrogram. Methods and results 3D shell of the heart was generated, and the NT was made trackable in the EAM system. Unipolar NT electrogram was continuously monitored. Penetration into pericardial sac was determined by an increase in NT potential amplitude and an injury current. A long guidewire of which the tip was also visible in the EAM system was advanced to confirm EA. Epicardial access was successfully obtained without complication in 13 pigs and 22 patients. In the animals, NT potential amplitude was 3.2 ± 1.0 mV when it was located in mediastinum, 5.2 ± 1.6 mV when in contact with fibrous pericardium, and 9.8 ± 2.8 mV after penetrating into pericardial sac (all P ≤ 0.001). In human subjects, it measured 1.54 ± 0.40 mV, 3.61 ± 1.08 mV, and 7.15 ± 2.88 mV, respectively (all P < 0.001). Fluoroscopy time decreased in every 4–5 cases (64 ± 15, 23 ± 17, and 0 s for animals 1–4, 5–8, 9–13, respectively, P = 0.01; 44 ± 23, 31 ± 18, 4±7 s for patients 1–7, 8–14, 15–22, respectively, P < 0.001). In five pigs and seven patients, EA was obtained without X-ray exposure. Conclusion By tracking NT in the 3D EAM system and continuously monitoring the NT electrogram, it is feasible and safe to obtain EA with minimum or no fluoroscopic guidance.

Background: While spontaneous coronary artery dissection (SCAD) patients can present with ventricular arrhythmias (VAs), the in-hospital outcomes among these patients are not well-established. Objective: This study aimed to analyze the in-hospital outcomes of patients with SCAD and concurrent VAs, and to determine the predictors of VAs occurrence in this population. Methods: Using the Nationwide Readmissions Database, our study included patients aged 18 years or older who had SCAD between 2017 and 2020. We categorized the cohort into two groups depending on the presence of VAs during hospitalization. The in-hospital outcomes were assessed between two groups. Through multivariable analysis, we further analyzed the predictors of VAs occurrence among SCAD patients. Results: Our study included 160 (13.45%) SCAD patients with concurrent VAs and 1,030 (86.55%) SCAD patients without concurrent VAs between 2017 and 2020. SCAD patients with concurrent VA were associated with higher rates of early mortality (11.88% vs. 2.04%, p<0.01), prolonged index hospital stay (≥7 days) (31.25% vs. 12.82%, p<0.01), and non-home discharge (21.88% vs. 6.50%, p<0.01). The length of hospital stay was longer in the SCAD with concurrent VAs group (6.93 days vs. 3.73 days, p<0.01), and the median cumulative cost of hospitalization was also higher in this group ($31,450 vs. $14,664, p<0.01). SCAD with concurrent VAs patients also had poorer in-hospital adverse events. In multivariable analysis, the independent predictors for VAs occurrence among SCAD patients were chronic liver disease (aOR: 2.18; 95% CI: 1.15- 4.12, p=0.02) and heart failure (aOR: 3.40; 95%CI: 2.30- 5.02, p<0.01). Conclusion: Ventricular arrhythmias among SCAD patients were associated with poorer in-hospital outcomes. Heart failure and chronic liver disease were the predictors of VAs in SCAD patients. This highlights the importance of closely monitor and aggressive VAs management among these high-risk patients.

AbstractBackgroundDisruption of central circadian rhythms likely mediated by changes in microbiota and a decrease in gut-derived metabolites like short chain fatty acids (SCFAs) negatively impacts colonic barrier homeostasis. We aimed to explore the effects of isolated peripheral colonic circadian disruption on the colonic barrier in a mouse model of colitis and explore the mechanisms, including intestinal microbiota community structure and function.MethodsColon epithelial cell circadian rhythms were conditionally genetically disrupted in mice: TS4Cre-BMAL1lox (cBMAL1KO) with TS4Cre as control animals. Colitis was induced through 5 days of 2% dextran sulfate sodium (DSS). Disease activity index and intestinal barrier were assessed, as were fecal microbiota and metabolites.ResultsColitis symptoms were worse in mice with peripheral circadian disruption (cBMAL1KO). Specifically, the disease activity index and intestinal permeability were significantly higher in circadian-disrupted mice compared with control animals (TS4Cre) (P &lt; .05). The worsening of colitis appears to be mediated, in part, through JAK (Janus kinase)-mediated STAT3 (signal transducer and activator of transcription 3), which was significantly elevated in circadian-disrupted (cBMAL1KO) mice treated with DSS (P &lt; .05). Circadian-disrupted (cBMAL1KO) mice also had decreased SCFA metabolite concentrations and decreased relative abundances of SCFA-producing bacteria in their stool when compared with control animals (TS4Cre).ConclusionsDisruption of intestinal circadian rhythms in colonic epithelial cells promoted more severe colitis, increased inflammatory mediators (STAT3 [signal transducer and activator of transcription 3]), and decreased gut microbiota–derived SCFAs compared with DSS alone. Further investigation elucidating the molecular mechanisms behind these findings could provide novel circadian directed targets and strategies in the treatment of inflammatory bowel disease.

Background: Ablation of ventricular tachycardia (VT) is limited by the inability to create penetrating lesions to reach intramyocardial origins. Intramural needle ablation using in-catheter, heated saline-enhanced radio frequency (SERF) energy uses convective heating to increase heat transfer and produce deeper, controllable lesions at intramural targets. This first-in-human trial was designed to evaluate the safety and efficacy of SERF needle ablation in patients with refractory VT. Methods: Thirty-two subjects from 6 centers underwent needle electrode ablation. Each had recurrent drug-refractory monomorphic VT after implantable cardioverter defibrillator implantation and prior standard ablation. During the SERF study procedure, one or more VTs were induced and mapped. The SERF needle catheter was used to create intramural lesions at targeted VT site(s). Acute procedural success was defined as noninducibility of the clinical VT after the procedure. Patients underwent follow-up at 30 days, and 3 and 6 months, with implantable cardioverter defibrillator interrogation at follow-up to determine VT recurrence. Results: These refractory VT patients (91% male, 66±10 years, ejection fraction 35±11%; 56% ischemic, and 44% nonischemic) had a median of 45 device therapies (shock/antitachycardia pacing) for VT in the 3 to 6 months pre-SERF ablation. The study catheter was used to deliver an average of 10±5 lesions per case, with an average of 430±295 seconds of radiofrequency time, 122±65 minute of catheter use time, and a procedural duration of 4.3±1.3 hours. Acute procedural success was 97% for eliminating the clinical VT. At average follow-up of 5 months (n=32), device therapies were reduced by 89%. Complications included 2 periprocedural deaths: an embolic mesenteric infarct and cardiogenic shock, 2 mild strokes, and a pericardial effusion treated with pericardiocentesis (n=1). Conclusions: Intramural heated saline needle ablation showed complete acute and satisfactory mid-term control of difficult VTs failing 1 to 5 prior ablations and drug therapy. Further study is warranted to define safety and longer-term efficacy. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT03628534 and NCT02994446.