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Background: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR), an impedance threshold device (ITD) and controlled, gradual, automated head and thorax elevation, collectively termed automated Head Up Position (AHUP) CPR, increases cerebral perfusion pressure (CerPP), brain blood flow, coronary perfusion pressure (CorPP), end tidal CO2 (ETCO2) and cerebral oximetry (rSO2) in animal models when compared with conventional (C) CPR. AHUP-CPR in patients is associated with increased neurologically favorable survival versus C-CPR. This study tested the hypothesis that AHUP CPR will increase cardiac stroke volume (SV) and other hemodynamics compared with C-CPR in a porcine model of cardiac arrest. Methods: Farm pigs (n=15) were sedated, anesthetized, and ventilated. Hemodynamics, including intracardiac conductance catheter based biventricular (BiV) pressure-volume (PV) loops, were continuously measured and recorded. After 10 minutes of untreated ventricular fibrillation, C-CPR was performed for 2 minutes in the supine position using an automated CPR device designed for pigs at a rate of 100 compressions/minute, depth of 21% of the chest antero-postero diameter, a 50% duty cycle, and no active decompression. ACD+ITD was then performed with 3 cm of active decompression for 2 minutes, followed by AHUP-CPR, where the head and thorax were initially raised to 10 cm and 8 cm for a 2-minute priming phase, followed by elevation over the next 2 minutes to 24 cm and 9 cm. A linear mixed-effects model with a random intercept for individual pigs was used for statistical analysis. Results: CerPP, CorPP, ETCO2, and rSO2, as well as BiV SV and cardiac output, increased progressively and significantly with implementation of AHUP-CPR (p<0.05). C-CPR generated a right ventricular (RV) SV of 25.0 mL (48% of baseline pre-VF) and left ventricular (LV) SV of 17.5 mL (39% of baseline). ACD+ITD significantly increased RV and LV SV by an average of ~ 48% versus C-CPR; AHUP-CPR further increased BiV SV by an average of ~ 83%, reaching 85% and 75% of RV and LV pre-VF values, respectively. (Figure 1) Conclusion: This study demonstrated biventricular stroke volume is significantly augmented with AHUP-CPR versus C-CPR or ACD+ITD in the flat position. These findings, together with AHUP-enhanced higher ETCO2, rSO2, and CerPP values versus C-CPR or ACD-CPR in the flat position, help explain the improved clinical outcomes associated with early use of AHUP-CPR.

Background: Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) combined with an impedance threshold device (ITD) and controlled head-up positioning, collectively termed AHUP-CPR, is associated with improved outcomes compared with conventional CPR (C-CPR). Active decompression (AD) forcibly lifts the anterior chest wall with suction after each compression, while the ITD simultaneously impedes airflow into the lungs. AD and ITD synergistically lower intrathoracic pressure during decompression, improving venous return, ventricular refilling and cardiac output. Concurrently, head-up positioning lowers intracranial pressures and improves cardiac preload. This pig study focused on the physiological role of AD during AHUP-CPR, simulating real clinical scenarios. Methods: Ten male and female farm pigs (~40 kg) were anesthetized, intubated and ventilated. Hemodynamic parameters, end-tidal CO2 (ETCO2), and biventricular pressure-volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins. Then, after 2 min of automated C-CPR in the flat position, AHUP-CPR with a 3 cm lift above the neutral position of the chest was performed for 13 min. AD was then abruptly discontinued, restarted 1 min later, and increased incrementally every min to up to 4 cm of active lift. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs. Results: Upon cessation of AD, coronary and cerebral perfusion pressures, compression and decompression aortic pressures, compression right atrial pressure, ETCO2, right and left ventricular preload, compliance, stroke volume and cardiac output all decreased immediately and significantly (p<0.01), whereas decompression right atrial and biventricular pressures increased. With restoration of AD, physiological parameters returned to ≥ 90% of pre-AD discontinuation values (Figures 1 and 2). Conclusion: Full chest wall lift, achieved with > 3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. After pausing AD, incremental restoration of AD resulted in nearly complete restoration of peripheral and central hemodynamic measures. These observations support the benefit of and need for ≥3 cm of AD to optimize AHUP-CPR. Effective means to generate ≥3 cm of AD should be considered when implementing and developing AHUP-CPR devices to optimize outcomes.

Background: Patients with Fontan palliation have reduced aerobic capacity because of impaired cardiac, pulmonary, and skeletal muscle function. However, the assessment of aerobic capacity in this population still relies on comparisons with people without cardiovascular disease, rather than comparison with the expected aerobic capacity of other Fontan patients. The purpose of this study was to determine the expected aerobic capacity of adults with Fontan palliation. Method: Adults with Fontan palliation who underwent cardiopulmonary exercise test at Mayo Clinic (2003-2023) were stratified into quartiles based on the predicted peak VO 2 . We assessed the correlates of predicted peak VO 2 , and the relationship between predicted peak VO 2 quartiles and cardiovascular outcomes (death/transplant). Results: Of 323 patients (age 29±9 years; 177 [55%] men), the median peak VO2 was 19.1 (15.2 - 23.9) ml/kg/min, and this corresponds to a predicted peak VO 2 of 51% (range 19 -88; interquartile range 41 - 62). The correlates of higher predicted peak VO 2 were smaller body mass index, higher systemic saturation, and lower Fontan pressures. The top, 2 nd ,3 rd , and bottom quartile of predicted peak VO 2 corresponds to predicted peak VO 2 of 63-88%, 51-62%, 41-50%, and 19-40%, respectively. Using the top quartile as the reference, the 3 rd quartile (HR 1.13, 95% CI 1.03-1.28, p=0.02), and 4 th quartile were associated with a higher risk of death/transplant (HR 1.32, 95% CI 1.16-1.69, p<0.001). Conclusions: The results of the current study would help calibrate the interpretation of exercise test data in adults with Fontan palliation and improve risk stratification in this population.

Background: Addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to automated head-up position (AHUP) cardiopulmonary resuscitation (CPR), the combination of active compression decompression CPR, an impedance threshold device, and controlled gradual elevation of the head and thorax, increases cerebral perfusion pressure. Optimal management of REBOA deflation after prolonged AHUP-CPR and ROSC is unknown. Hypothesis: We hypothesized that partial deflation of REBOA, rather than full deflation after ROSC, would result in better hemodynamic parameters. Aims: To compare hemodynamic parameters 1 minute before and 1 minute after complete (100%) versus partial (50%) REBOA deflation after prolonged AHUP-CPR and ROSC. Methods: Yorkshire pigs weighing ∼40 kg were anesthetized and ventilated. After 10 minutes of untreated ventricular fibrillation, AHUP-CPR was started and continued for a median time of 44 minutes. After ROSC, REBOA deflation was initiated in two ways: complete (100%) or partial (50%) deflation over 5 seconds. The following hemodynamic parameters were measured 1 minute before and 1 minute after deflation: mean aortic pressure (MAP), cerebral perfusion pressure (CerPP), and coronary perfusion pressure (CorPP). Data, in mmHg, are presented as mean ± SD, and compared using a paired t-test. Results: 13 pigs were included, with 8 pigs in the 100% deflation group and 5 in the 50% deflation group. After ROSC in the 100% deflation group, MAP was 81.5±36.0 before deflation vs. 43.0±14.4 after (p=0.01), whereas in the 50% deflation group, MAP was 90.5±33.0 vs. 83.4±33.3 (p=0.02). CerPP was 72.3±34.4 before deflation vs. 35.9±14.6 (p=0.01) in the 100% deflation group, and 84.6±31.2 vs. 77.6±31.8 (p=0.02) with 50% deflation. Similarly, CorPP was 74.1±37.3 before deflation vs. 36.1±15.8 (p=0.01) after in the 100% deflation group, and 83.0±32.7 vs. 76.1±33.0 (p=0.02) in the 50% deflation group. The differences from before to after deflation were markedly less in the 50% deflation group versus the 100% deflation group: MAP (7.0±4.3 vs. 38.5±25.7, p=0.02), CerPP (7.1±4.4 vs. 36.3±24.4, p=0.02), and CorPP (6.0±4.2 vs. 39.8±25.2, p=0.02), respectively. Conclusion: In this porcine model of prolonged cardiac arrest, partial deflation of the REBOA balloon post ROSC resulted in strikingly higher hemodynamics compared with complete deflation. These findings highlight the need to develop a post-ROSC REBOA deflation strategy when used during AHUP-CPR.

Background: Patients with adult congenital heart disease (ACHD) form a unique subset of patients with complex ventricular tachycardia (VT). Objective: To evaluate the clinical and procedural characteristics and outcomes of patients with congenital heart disease who present for VT ablation. Methods: A single-center, retrospective study of patients undergoing VT ablation was conducted. The primary composite outcome was recurrent monomorphic VT, and repeat ablation. Results: Out of 508 procedures for ventricular tachycardia ablation, 37 were performed in ACHD patients. These patients were younger compared to the non-ACHD subtype.(Table 1). Out of 26 patients with congenital heart disease, a majority had a diagnosis of tetralogy of Fallot (57.6%) and 69% had 2-3 prior open-heart surgeries, including ventriculotomy (53.8%), ventricular septal defect repair (65.3%), and pulmonary valve replacement (57.6%) (Table2). They had a higher mean LVEF,and lower burden of comorbidities including hypertension, chronic kidney disease, and myocardial infarction compared to their non-ACHD counterparts and had been on fewer antiarrhythmics at baseline. ACHD patients were less likely to require epicardial access, but the requirement for induction meds was higher, and energy delivery times were longer. There were no significant differences in the VT characteristics and mapping techniques between the two groups. There were no significant differences in outcomes including complications, and time to recurrence, and a Kaplan-Meier analysis showed no significant difference in VT free survival when ACHD patients were compared to patients without ACHD (Figure 3). After adjusting for age, sex and comorbidities, ACHD was not a predictor of having VT recurrence or repeat ablation (aHR =1.1 (0.7-1.9), p=0.6) Conclusion: VT ablation in patients with ACHD is safe, and as effective as ablation in non-ACHD patients. Procedure times tend to be longer owing to a more challenging substrate.

Background: We previously developed deep-learning algorithms that identify coronary artery disease (CAD) risk based on (i) coronary artery calcium (CAC), (ii) obstructive CAD by angiography, and (iii) left ventricular akinesis in ≥1 segment by echocardiogram, using a 12-lead electrocardiogram (CAD ECG-AI). We tested the hypothesis that those with increased probability of CAD by CAD ECG-AI algorithms will have an increased risk of atherosclerotic cardiovascular disease (ASCVD) events and would refine the AHA Predicting Risk of Cardiovascular Disease Events (PREVENT TM ) equations’ predictive capabilities. Methods: We assessed a group of consecutive patients who sought primary care in Olmsted County, MN, between 1997 and 2003. Passive follow-up was conducted using the Rochester Epidemiology Project's record linkage system. Patients included met the same criteria of the original PREVENT TM equations. The probability output of each CAD ECG-AI algorithm was used to predict ASCVD (fatal and non-fatal myocardial infarction and ischemic stroke) and ASCVD-Plus [further including percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and all-cause mortality]. Events were validated in duplicate. Cox proportional hazard models adjusted for age, sex, and risk factors while modeling each CAD ECG-AI algorithm as an individual and additive predictor (see footnote). PREVENT TM risk categories stratified analysis to evaluate the effect of the CAD ECG-AI models on predicted ASCVD risk. Results: We included 21,193 patients, with mean ± SD age 51.6 ± 12.0, 54% women and 95% white. After 14.2±12.4 years follow-up, 1,351 (6.4%) developed ASCVD, and 2,808 (13.2%) had ASCVD-Plus. The risk of ASCVD and ASCVD-Plus increased with positivity for the CAD ECG-AI algorithms after adjustments for age, sex, and PREVENT TM equations factors, all p for trend <0.001 (data not shown). In additive analyses, the risk of ASCVD and ASCVD-Plus increased with increased CAD ECG-AI factors, all p for trend <0.001 ( Fig. A-B ). Furthermore, the CAD ECG-AI algorithm enhanced the predictive capabilities of PREVENT TM equations across most risk subgroups ( Fig. C-E ). Conclusions: The deep-learning CAD ECG-AI algorithms displayed an independent and additive association with long-term ASCVD and ASCVD-Plus events in the community and improved the PREVENT TM predicted ASCVD risk. The CAD ECG-AI algorithms could help identify individuals at risk in primary prevention of cardiovascular events.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have known cardiovascular benefits. We aimed to assess the efficacy of GLP1-RA or SGLT2i initiation in reducing mortality or cardiovascular events in a community-based cohort of adults with ischemic stroke. Methods: Patients ≥18 years old admitted for acute ischemic stroke between Jan 2000 and June 2022 were identified using the Rochester Epidemiology Project. Subjects were considered exposed to SGLT-2i or GLP1-RA if they were treated with either medication after the index stroke and before the primary (all-cause mortality) or secondary outcomes (MI, recurrent ischemic stroke or composite). Kaplan-Meier curves and Cox models are shown in the Figures . Results: We included 7044 subjects, mean age 72±14 yr, 52% male, 94% white, over a median follow-up of 3 [1-7] years, 416 subjects (6%) had a second stroke, 426 (6%) had an incident MI and 3738 (53%) died. Those on SGLT2i/GLP1-RA had a decreased risk for mortality, incident MI, and composite in the univariate analysis. These associations remained significant after multivariable adjustment and were not affected by minimum time of exposure Figure 1&2 . SGLT2i/GLP1-RA use was associated with recurrent ischemic stroke in the multivariate analysis Figure 2C . All associations remained significant in most sub-analyses of individual medications except for the association between GLP1-RA and recurrent stroke Figure 3 Conclusions: SGLT2i or GLP-1 RA use was associated with decreased mortality and risk of myocardial infarction and recurrent stroke in patients with ischemic stroke.

Background: Many children born with single ventricle physiology are palliated with Fontan operation, which may include a fenestration creation. This has been demonstrated to improve short-term outcomes after surgery. Reduced exercise capacity has been shown to be a predictor of prognosis in Fontan patients. Aim: We sought to compare cardiopulmonary exercise test (CPET) data between fenestrated and non-fenestrated Fontan patients. Methods: We conducted a retrospective cohort study of 185 patients referred for CPET from 2011 to 2024. Patients with complete CPET data were included. Type of Fontan, comorbidities, and echocardiogram data were ascertained electronically. Patients were divided into 2 different groups according to the fenestration patency. Fisher’s exact test or chi-square was used to compare categorical variables. T-test and Turkey-Kramer were used to compare continuous variables. Adjustment using General Lineal Models procedure were used to identify any confounder that could affect the results. P value <0.05 was considered significant. Results: 142 patients were classified in the non-fenestrated (NF) group, and 43 in the fenestrated group (FF). Baseline characteristics of both groups are shown in Table 1. From the evaluated CPET variables, the minute ventilation-carbon dioxide production (VE/VCO2) was higher in the FF (p=<0.001), and oxygen saturation at peak exercise (SatO2) was lower in this group (p= <0.001) (Figure 1). There was no significant difference between peak oxygen consumption (VO2) between groups. When adjusted by comorbidities only VE/VCO2 nadir, slope and peak SatO2 were statistically significant different between groups (Table 2). Conclusion: Ventilatory variables showed significant differences when fenestration was presented, secondary to V-Q mismatch from increased right to left shunt. Despite the theoretical advantage of increased cardiac output from Fontan fenestration, exercise performance was similar between both groups.

Background: Recent studies have reported associations between alterations in gut microbiome composition (GMC) and cardiovascular disease risk factors (CVR). However, data regarding the use of GMC as a biomarker of CVR is scarce. Aims: The current study was designed to assess the distinct patterns in GMC among patients with varying degrees of CVR and/or atherosclerotic cardiovascular disease (ASCVD). Methods: Patients with a range of CVR including hypertension (HTN), hyperlipidemia (HLD), diabetes (DM), and/or ASCVD referring to Mayo Clinic from 2013 to 2018 were prospectively enrolled. DNA extracted from stool samples was analyzed using the V3-V5 region of the 16s data. Microbial α-diversity was assessed by the observed taxonomic units, Shannon, and Chao1 indices. β-diversity was assessed using Bray-Curtis dissimilarity and plotted using principal coordinates analysis. Hierarchical clustering was used to identify patterns in the GMC samples. Random Forest analysis was used to identify the most important clinical factors differentiating the clusters. Results: A total of 211 patients with a median age of 60 [IQR: 50,70] years and with 90 (42.7%) males were included. Two clusters of GMC were identified (Figure 1A) . Cluster 1 and 2 had 104 (49.3%) and 107 (50.7%) patients, respectively. Among CVRs, age and body mass index were the most prominent factors contributing to the difference in GMC among clusters ( Figure 1B ). Cluster 2 had a better α diversity profile than Cluster 1 (Figure 1C-E) . There was no significant difference in TMAO between clusters (P=0.6). Cluster 2 patients were younger (P<0.001), leaner (P=0.007), more physically active (P<0.001), less male (P=0.009), and had a lower prevalence of ASCVD (P=0.003), HTN (P=0.010), and HLD (P=0.005). There was no significant difference in the prevalence of DM (P=0.063), smoking (P=0.446), and alcohol intake (P=0.134) between the clusters. Conclusion: This study suggests the potential of GMC profiling as a valuable biomarker for assessing CVRs, with age and BMI as the most prominent factors associated with GMC clustering.

Introduction: Endothelin receptor antagonists (ERAs) are the mainstay therapy for pulmonary arterial hypertension (PAH). However, there is limited data on cardiac adverse drug events (ADEs) associated with ERA medications. We performed a pharmacovigilance study comparing bosentan and ambrisentan using the FDA Adverse Event Reporting System (FAERS) data. Methods: Cardiac ADE data for bosentan and ambrisentan from January 1, 2004, to December 31, 2023, in the FAERS database were retrieved. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) aligned with p-values. The following cardiac ADEs were included: atrial fibrillation (AF), right ventricular failure (RVF), and cardiac arrest (CA). Results: For adults ≥ 18 years, a total of 12,058 cardiac ADEs were reported for both bosentan (38%) and ambrisentan (62%). Among the selected cardiac ADEs, AF was more frequently reported with bosentan (ROR 3.99, 95% CI: 3.62-4.40) than ambrisentan (ROR 1.91, 95% CI: 1.77-2.07). RVF showed a significantly higher ROR for bosentan (73.60, 95% CI: 66.68-81.25) than ambrisentan (23.11, 95% CI: 20.99-25.46). CA was also more commonly associated with bosentan (ROR 2.25, 95% CI: 1.98-2.55) than with ambrisentan (ROR 0.69, 95% CI: 0.61-0.78), with all comparisons showing p-values < 0.001. Conclusion: Our study identifies a significantly higher frequency of cardiac ADEs, particularly AF, RVF, and CA, in patients treated with bosentan compared to ambrisentan. This finding corroborates previous literature that has suggested differential safety profiles among ERAs, emphasizing the need for vigilant cardiac monitoring. Clinicians should integrate these insights into their practice, potentially favoring ambrisentan in patients with elevated cardiac risk, thus optimizing the management of PAH and improving patient outcomes.