Abstract 4139333: An Echocardiogram-Based Risk Model to Predict Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation, Volume 150, Issue Suppl_1, Page A4139333-A4139333, November 12, 2024. Background:Atrial fibrillation (AF) is often asymptomatic and detection of AF is challenging. 2D-Echocardiogram (2DE) provides a comprehensive assessment of cardiac structure and function, and hence, may be used to predict AF.Aim: To derive a 2DE-based risk model to predict AF using supervised machine learning (ML).Methods:We included 5,445 older adults from the Atherosclerosis Risk in Communities (ARIC) study who underwent transthoracic 2DE at baseline (visit 5, 2011-2013) and had no known history of AF. Individuals were randomly allocated to the training and testing sets in a 7:3 ratio. Incident AF was ascertained from hospitalization records and death certificate during follow-up. Missing values of 2DE measures with

Read More

Abstract 4141522: VTRNA 2-1 Promoter Methylation and HDL as Predictors of Excess Weight Loss After Bariatric Surgery: The Influence of Maternal Nutrition

Circulation, Volume 150, Issue Suppl_1, Page A4141522-A4141522, November 12, 2024. Background:Maternal nutritional status and periconceptional environmental conditions have been previously linked to the methylation of the vtRNA 2-1 promoter. Bariatric surgery is an effective treatment for morbid obesity, with most patients achieving significant weight control within 1-2 years post-surgery. However, some patients do not experience the desired weight loss. The clinical correlation between the methylation of the vtRNA 2-1 promoter and postoperative outcomes in obese patients remains unclear. This study aims to elucidate the relationship between the methylation of the vtRNA 2-1 promoter and the effectiveness of bariatric surgery.Hypothesis:The degree of methylation of the vtRNA 2-1 promoter is related to excess weight loss (EWL) after bariatric surgery.Methods:The OCEAN registry (Obesity and Clock for Elegant AgiNg) is a prospective cohort study collecting data from 2011 to 2017, including 381 obese patients, 179 of whom underwent bariatric surgery. Quantitative pyrosequencing was performed on all patients. Postoperative weight and EWL were tracked and recorded at 3, 6, 12, and 24 months. Statistical analyses were conducted using SPSS.26.Results:The degree of methylation of the vtRNA 2-1 promoter shows a bimodal distribution. Compared to the normal group from the Taiwan Biobank, the methylation distribution between the two groups differs significantly. Patients were categorized into hypomethylation (≤10%), intermediate-methylation (10-40%), and hypermethylation (≥40%) groups. Statistics indicate that hypermethylation is associated with higher EWL at one year (p=0 .047) and two years (p=0.04) post-surgery compared to the hypomethylation group. In the linear regression model, after controlling for variables including age, creatinine, cholesterol, TG, LDL, AC sugar and HbA1c, our analysis revealed a positive correlation between HDL and one year EWL.Conclusion:Obese patients who have hypermethylation of the vtRNA 2-1 promoter demonstrate improved EWL one and two years following bariatric surgery. Given the previous links between the methylation of the vtRNA 2-1 promoter and maternal nutritional status, these findings suggest that early life nutritional factors may influence the effectiveness of bariatric surgery outcomes. Further comprehensive and long-term studies are needed to confirm the methylation of the vtRNA 2-1 promoter as a viable indicator for predicting bariatric surgery outcomes and improving cardiovascular health.

Read More

Abstract 4126628: Worse Cardiac Structure and Function is Associated with Decline in Multiple Domains of Cognitive Function: the Atherosclerosis Risk in Communities (ARIC) Study

Circulation, Volume 150, Issue Suppl_1, Page A4126628-A4126628, November 12, 2024. Background:Cognitive impairment is cross-sectionally associated with worse cardiac structure/function. However, limited data exist regarding cardiac structure/function and longitudinal changes in cognitive function.Objective:Determine the association of cardiac structure and function with longitudinal changes in cognitive performance in late life.Methods:Among HF- and dementia-free participants in the community-based ARIC study who attended the 5th study visit (V5; 2011-2013), underwent protocol echocardiography, and completed a neurocognitive test battery at both V5 and study Visit 6 (V6; 2015-17), we assessed associations of cardiac structure and function measures with changes in both domain-specific and global cognitive scores between V5 and V6 using multivariable linear regression. Models were initially adjusted for demographics and education level, with additional models further adjusting for cardiovascular risk factors and disease at both V5 and V6. The neuropsychological test battery consisted of 10 neuropsychological tests that covered 3 domains of cognitive function: memory, executive functioning, and language. Factor scores were constructed for each cognitive domain, and their average represented a global composite score.Results:Among 2,988 included participants, mean age was 74±5 years, 60% were female, 20% reported Black race, and mean LVEF was 66±6%. Over a mean of 4.9±0.6 years (the V5 to V6 interval), raw scores declined for all neuropsychological tests. In fully adjusted models, worse diastolic function (larger LAVi) and LV remodeling (greater LV mass index) were associated with decline in executive function. Lower LVEF was associated with decline in language function, while worse LV longitudinal strain – a more sensitive measure of systolic dysfunction – was associated with decline in executive function, language function, and global cognition performance (all p

Read More

Abstract 4145433: The Association of PREVENT-HF Risk Estimates with Subclinical (Stage B) HF and Clinical Implications for HF Risk: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation, Volume 150, Issue Suppl_1, Page A4145433-A4145433, November 12, 2024. Background:PREVENT-HF is a risk prediction tool recently developed by the AHA to estimate heart failure (HF) risk. The association of PREVENT-HF with measures of subclinical HF (stage B HF), and the clinical implications of subclinical HF measures within PREVENT-HF categories are undefined.Methods:We performed a prospective analysis of 2,716 ARIC participants

Read More

Abstract 4142703: Characteristics and Transplant Outcomes of Patients with End Stage Hypertrophic Cardiomyopathy Stratified By Genotype

Circulation, Volume 150, Issue Suppl_1, Page A4142703-A4142703, November 12, 2024. Introduction:Harboring a likely pathogenic/pathogenic (LP/P) sarcomeric genetic variant has been shown to be a predictor of developing hypertrophic cardiomyopathy (HCM) with systolic dysfunction. There are limited data describing the associations between genotype and clinical outcomes of patients with end stage HCM.Methods:All patients with HCM who underwent both genetic testing and heart transplantation (HT) between 2011 and 2023 at a quaternary care center were included. Baseline characteristics, peri-HT management and outcomes were compared between patients with or without LP/P variants for HCM using summary statistics and survival analysis.Results:Between 2011 and 2023, 38 patients with HCM were transplanted. Of these 38, 29 patients underwent genetic testing, and LP/P variants thought to be casual for HCM were identified in 20 (Gene+) (Table 1). Female patients composed 40% of the Gene+ cohort compared to 89% of the gene-negative (Gene-) cohort (p=0.04). The majority of LP/P variants were inMYH7(7/20) andMYBPC3(5/20). Pre-transplant cardiometabolic comorbidities were prevalent in both groups. Pre-transplant LVEFs were not significantly different (47% [IQR 34.0, 57.5] in Gene+; 55% [IQR 42.0, 60.0] in Gene-; p=0.23). Pre-transplant medication management and bridge to transplant strategies were similar between the two groups. NYHA Class at time of HT was higher in the Gene+ cohort (p=0.04), though a similar percentage of patients in both cohorts were upgraded to higher UNOS statuses while on the waitlist. Survival at 30, 90 and 180-days after HT (Figure) and incidence of rejection during the year following HT were similar in both cohorts (Table 2).Conclusion:Further investigation is needed to elucidate the impact of genotype on outcomes in end stage HCM.

Read More

Abstract 4137594: Intrinsic Capacity Trajectories and Cardiovascular Disease Among Chinese Older Adults: A Population-Based Longitudinal Study

Circulation, Volume 150, Issue Suppl_1, Page A4137594-A4137594, November 12, 2024. Background:WHO defined intrinsic capacity (IC), a composite of physical and mental capacities, is a marker of healthy aging. Monitoring IC trajectories in older adults may guide preventative strategies and delay negative health outcomes. With the rapidly increasing proportion of older adults and the high prevalence of cardiovascular disease (CVD) in China, this study aimed to identify IC trajectories over time and determine whether IC trajectories can predict CVD outcomes.Hypothesis:The IC trajectory among Chinese older adults is heterogeneous; the decline of IC will be associated with increased CVD.Methods:The study used data from five waves (2011 to 2020) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 3,336 adults aged 60 years or older without CVD during the baseline survey in 2011 (T1), who completed the follow-ups in 2013 (T2) and 2015 (T3) were included to determine IC trajectory. IC was assessed through five domains (locomotion, sensory, vitality, cognition, and psychology) using the WHO framework. The CVD outcomes were determined by self-reported diagnoses of heart disease or stroke in the 2020 (T5) wave. A group-based trajectory model (GBTM) was used to identify IC trajectory, and logistic regression was employed to explore the association between IC trajectory groups and CVD outcomes adjusting for covariates.Results:Three IC trajectory groups were identified (Fig 1): high IC-stable group (13.40%), medium IC-stable group (56.12%), and low IC-decline group (30.48%). By the 2020 follow-up, 1204 participants (36.1%) reported CVD diagnosis. Adjusted for sociodemographic, lifestyle factors (smoking, drinking), and cardiovascular metabolic factors (hypertension, diabetes, dyslipidemia), compared to the high IC-stable group, the low IC-decline group had 63.7% higher odds of CVD (OR=1.637, 95%CI=1.268-2.114), and medium IC-stable group had 7.1% higher odds of CVD (OR=1.071, 95%CI=0.851-1.349).Conclusion:IC trajectory among Chinese older adults is heterogeneous, and IC declines predict higher odds of CVD onset. Regular monitoring of IC and tailored intervention to improve IC may facilitate CVD prevention.

Read More

Abstract 4142090: Venous Access Alone vs. Arterial and Venous Access for Patent Arterial Duct Device Closure in Childhood

Circulation, Volume 150, Issue Suppl_1, Page A4142090-A4142090, November 12, 2024. Background:The persistently patent arterial duct accounts for ~12% of congenital heart lesions. Untreated, it may result in heart failure due to volume loading of the left heart, pulmonary hypertension, and infective endarteritis. Percutaneous device closure is the preferred occlusion technique, with the standard approach consisting of femoral artery access for angiography and venous access for device delivery (AA). A venous-only strategy (VA) for angiography and device delivery can also be employed.Hypothesis:We hypothesized that VA would eliminate arterial complications, and reduce procedure times and radiation exposure compared to standard AA.Methods:This retrospective cohort study reviewed isolated arterial duct device closures at the Hospital for Sick Children from January 1, 2011 through December 31, 2022. Exclusions included premature neonates, children requiring arterial access for monitoring and those who underwent other procedures. Children were categorized based upon initial access determined by operator preference, into VA or AA groups.Results:The cohort consisted of 405 children, 252 (62.2%) females, with a median age of 3.1 years (IQR1.30–5.84), median weight 13.2kg (IQR 9.0–19.5), and duct diameter of 2.9mm (IQR 2.0–3.5) with no significant differences between the groups. Type A ducts were more frequent in the AA group (90% vs. 72%). The VA group included 106 children, of which 14 (13.2%) required AA conversion for angiography due to complex anatomy, to assess device positon prior to release, but remained in the VA group for analysis.Children in the VA group had lower dose area product (DAP) (p

Read More

Abstract 4145413: Factors Associated with Long Term Adverse Limb Events after Endovascular Revascularization: The Boston Femoral Artery Endovascular Revascularization Outcomes (FAROUT) study

Circulation, Volume 150, Issue Suppl_1, Page A4145413-A4145413, November 12, 2024. Background:Patient, lesion, and procedural characteristics may impact the long-term risks of adverse limb outcomes differently after successful endovascular revascularization for lower extremity peripheral artery disease.Objective:To assess the relationships of patient, lesion, and procedural characteristics to the subsequent risk of major and minor adverse limb events over the decade after successful endovascular revascularization of the superficial femoral artery for chronic limb threatening ischemia (CLTI) or lifestyle limiting claudication.Methods :A retrospective cohort of patients who underwent endovascular revascularization between 2003-2011 were followed for a median of 9.3 (25-75%: 6.8, 11.1) years. Hazard ratios and 95% confidence intervals (HR, 95% CI) from Cox proportional hazards models assessed the risk of major adverse limb events (MALE) or minor revascularization, MALE alone, and minor revascularization alone.Results:There were 232 index limb revascularizations in 185 patients. Longer lesion length was associated with a higher risk of MALE or minor revascularization (HR=2.09, 95% CI=1.22, 3.60) and minor revascularization alone (HR=2.53, 95% CI=1.39, 4.61). Current smoking was linked with minor revascularization (HR=3.83, 95% CI=1.54, 9.56). CLTI was associated with MALE or minor revascularization (HR=1.89, 95% CI=1.09, 3.29), and MALE alone (HR=7.43, 95% CI=3.11, 17.79). Black race/ethnicity (HR=4.74, 95% CI=1.51, 14.9) and low density lipoprotein (LDL) >100 mg/dL (HR=2.76, 95% CI=1.20, 6.35) were linked to MALE alone.ConclusionFactors related to MALE differed from those related to minor revascularization. Lesion length and smoking were linked to minor revascularization, whereas CLTI, Black race/ethnicity and elevated LDL were linked to MALE.

Read More

Abstract 4136016: Higher aircraft noise exposure associates with worse heart structure and function

Circulation, Volume 150, Issue Suppl_1, Page A4136016-A4136016, November 12, 2024. Introduction:Aircraft noise is a concern for communities living near airports, but its impact on heart structure and function is unknown.Methods:Night-time (Lnight) and weighted 24-hour day (Lden) aircraft noise levels were provided by the UK Civil Aviation Authority for 2011 (Fig.1). Health data came from UK Biobank (UKB) participants living near four UK major airports (Heathrow, Gatwick, Manchester, and Birmingham) who had cardiovascular magnetic resonance (CMR) imaging starting from 2014 and self-reported no hearing difficulties. Generalized linear models investigated the associations between aircraft noise exposure and CMR metrics (derived using a validated convolutional neural network to ensure consistent image segmentations), after adjustment for demographics, socio-economic, lifestyle, and environmental covariates. Mediation by cardiovascular (CV) risk factors was also explored. Downstream associations between CMR metrics and major adverse cardiac events (MACE) were tested in a separate prospective UKB subcohort (n=26,658) to understand the potential clinical impact of noise-associated heart remodeling.Results:Of 3,635 UKB participants included, 3% experienced higher aircraft noise Lnight(≥45decibels) and 8% higher Lden(≥50decibels). Participants exposed to higher Lnighthad 7% [95% confidence interval: 4–10%] higher left ventricular (LV) mass and 4% [2–5%] thicker LV walls with a normal septal:lateral wall thickness ratio (Fig.2 A1). This LV concentric remodeling is relevant since 7% higher LV mass associates with 32% higher odds of MACE. They also had worse LV myocardial dynamics (Fig.2 A2) (e.g., 8% [4–12%] lower global circumferential strain which associates with 37% higher odds of MACE). Overall, a hypothetical individual experiencing the typical CMR abnormalities associated with higher Lnightexposure may have 5-times higher odds of MACE. Body mass index and hypertension appeared to mediate 20-50% of the observed associations. Findings were similar in those exposed to higher Lden(Fig.2 B1-2). Participants who did not move home during follow-up and were continuously exposed to higher aircraft noise levels had the worst CMR phenotype.Conclusion:Higher aircraft noise exposure associates with adverse LV remodeling, potentially due to noise increasing the risk of obesity and hypertension. Findings are consistent with the existing literature on aircraft noise and CV disease, and need to be considered by policymakers and the aviation industry.

Read More

Abstract 4141564: Disparities in Healthcare Utilization following Endovascular Abdominal Aneurysm Repair

Circulation, Volume 150, Issue Suppl_1, Page A4141564-A4141564, November 12, 2024. Introduction:Healthcare utilization in postoperative management and surveillance following endovascular aneurysm repair (EVAR) is an important factor in achieving long-term treatment success. However, factors associated with poor healthcare utilization have yet to be elucidated.Hypothesis:Disadvantaged patients have lower rates of surveillance and higher rates of emergency health service use than their counterparts.Aims:Examine rates of healthcare utilization stratified by age, sex, race, dual-enrollment in Medicare and Medicaid, and residence in a distressed community.Methods:We performed an observational retrospective cohort study of Medicare beneficiaries who underwent infrarenal EVAR with a bifurcated endograft between 2011-2019. We examined annual rates of post-operative surveillance (EVAR-related outpatient visits, surveillance imaging), use of emergency department (ED) visits, and hospital readmission across several disparity measures using Modified Poisson Regression models.Results:In 111,381 Medicare beneficiaries undergoing EVAR, comorbidities associated with poor postoperative surveillance were chronic kidney disease (aRR:1.06[1.04-1.07]), heart failure (1.10[1.09-1.11]), hyperlipidemia (1.16[1.14-1.19]), hypertension (1.09[1.07-1.12]), and ischemic heart disease (1.15[1.14-1.17]). For EVAR-related office visits, patients with worse post-operative care included those >85 years, female, Black, dual-enrolled, or living in distressed communities (Table 1). Similarly, less surveillance imaging was performed in patients >85 years, dual-enrolled, or living in distressed communities. There was a greater need for ER care or readmission among patients >85 years, female, Black, dual-enrolled, or living in distressed communities.Conclusions:Our study revealed patterns of disparities in post-procedure EVAR-related office visits and EVAR imaging studies, and greater use of emergency health services associated with patient age, sex, race, and socioeconomic status. These findings may suggest barriers in access to appropriate surveillance and care which could be addressed by targeting the identified groups for intervention efforts to improve EVAR surveillance.

Read More

Abstract 4136202: Incident Hypertension and Survival Outcomes After Immune Checkpoint Inhibitor Initiation

Circulation, Volume 150, Issue Suppl_1, Page A4136202-A4136202, November 12, 2024. Introduction:Immune checkpoint inhibitors (ICIs) are commonly used as anticancer agents linked with dramatic antitumor response but are associated with cardiotoxicity. Recent isolated reports have suggested ICIs may link with hypertension (HTN) after years of treatment. Yet, the timing and long-term ramifications of this HTN are unknown.Methods:From a large cohort of well-phenotyped cancer patients treated with ICIs from 2011-2022, we assessed the incidence of new or worsened HTN [systolic blood pressure (SBP) ≥130 mmHg (or in a higher HTN stage) on two occasions within a three-month period or addition of an antihypertensive medication] after ICI initiation. Secondary endpoints included major cardiovascular events (MACE), defined as symptomatic arrhythmia, myocardial infarction, stroke, heart failure, or cardiac death. Observed incident HTN rates were compared to Framingham-predicted rates, using JNC 8 cutoffs of 140/90 mmHg. Landmark analysis, excluding patients who were observed to have new HTN but had SBPs ≥130 mmHg on two occasions within six-months prior to ICI initiation, identified patients with possible undiagnosed HTN. Multivariable regression and survival analysis were used to define factors associated with new worsened HTN and MACE and the relationship between SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of ICI-related HTN will be assessed.Results:Overall, from 312 patients treated with ICIs (mean age 63.5 years, 67.4% baseline HTN, 11.0% on dual ICI-therapy), 50.0% (156/312) developed new or worsened HTN over a mean of 27 months follow-up. Cumulative incidence of new HTN by 1-year was 50.0% wherein the mean peak increase in SBP was 12 mmHg. In landmark analysis, excluding those with undiagnosed HTN and applying the JNC 8 cutoff of ≥140/90 mmHg, the observed new HTN rate was 21.4% at 1 year, >2-fold higher than the Framingham-predicted rate of 9.3% (RR 2.3,P

Read More

Abstract 4147977: The association of Fontan fenestration patency on cardiopulmonary exercise performance in children and adults

Circulation, Volume 150, Issue Suppl_1, Page A4147977-A4147977, November 12, 2024. 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

Read More

Abstract 4147143: The value of high coronary artery calcium score (CACS) in prediction of stroke incidence.

Circulation, Volume 150, Issue Suppl_1, Page A4147143-A4147143, November 12, 2024. Introduction:In multiple recent studies, a higher coronary artery calcium score (CACS) has been associated with a higher risk of MACE and all-cause mortality. The relationship between coronary artery calcium (CAC) and the incidence of stroke is poorly defined.Method:Patients were obtained from the Sanford heart screening program from April 25, 2011 through June 23, 2023. The sample was limited to only those who underwent a CACS. A high CACS was deemed as anything greater than or equal to 300, whereas anything lower was identified as non-high CACS. The odds ratio was calculated via multiple logistic regression to analyze the data.Results:A total of 33249 patients with CACS were analyzed in this study. The average age of the patients is 56.19 (SD =9.97) and 46% of them are male. Among all the patients in the study, 3529 had a high CACS, of which 399 of them had stroke (11.3%). Our study shows that there is a positive effect between a high CACS and the incidence of stroke. The odds of having stroke are predicted to be 1.95 times larger in patients with high CACS (P-value < 0.001). In comparison to the patients who smoke frequently, the odds of developing a stroke shrink by a factor of about 0.53 and 0.48 for patients who do not smoke (P-value < 0.001) and patients who smoke occasionally (P-value=0.003), respectively. Furthermore, a five-year increase in age results in a 32% increase in odds of developing a stroke for patients with CACS less than 300 (P-value < 0.001), and a 17% increase in odds of developing a stroke for patients with high CACS (P-value = 0.006). However, for each additional year after CACS testing, the odds of stroke decreased by 18%, for patients with CACS less than 300 (P-value < 0.001), and 27%, for patients with high CACS (P-value < 0.001), likely due to interventions done.Conclusion:Our study showed that a high coronary artery calcium score predicts an increased incidence of stroke in our patient population.

Read More

Abstract 4146919: Delta-like Ligand 4 Inhibitors Induce Pulmonary Arterial Hypertension in Clinical Trials

Circulation, Volume 150, Issue Suppl_1, Page A4146919-A4146919, November 12, 2024. Background:Delta-Like Ligand 4 (DLL-4) blockade with therapeutic monoclonal antibodies is an emerging cancer treatment targeting tumor angiogenesis. Inhibition of DLL-4 within the pulmonary vasculature allows for unopposed JAG-1-NOTCH3 signaling, leading to pulmonary vascular smooth muscle (vSMC) cell proliferation and the development of pulmonary arterial hypertension (PAH).Hypothesis:Clinical trials using DLL-4 inhibitors may show an increased incidence of PAH as a side effect of the drugs tested.Aims:Review the PAH incidence as an adverse outcome in DLL-4 inhibitor clinical trials.Methods:Clinicaltrials.gov was queried for studies on DLL-4 inhibition. Patient demographics, medication regimens, trial methodology, and outcomes were recorded. Adverse events were categorized according to National Cancer Institute Common Terminology Criteria for Adverse Events. PAH grades were defined as ranging from mild dyspnea (Grade 1) to life-threatening airway consequences or death (Grade 4-5). Degree of PAH was determined by the clinical trial investigators. Echocardiography and cardiac catheterization were most widely used as PAH diagnostic modalities.Results:Thirteen clinical trials (Phase: 1[n=3], 1a[n=1], 1b[n=6], 2[n=3]) from 2011-2023 investigating DLL-4 or DLL-4/VEGF inhibitors were included. The most common antibody used was Demcizumab(6), followed by Navicixizumab(2), Dilpacimab(2), ABL001(2), and Enoticumab(1). A total of 672 patients (median age 60, 52.5% female) underwent treatment. There were 74 new PAH cases reported (average incidence of 11.7%[± 5.8%]). Four of seventy-four PAH patients also manifested LHF. PAH grades 1-2 represented 81% (n=60) of cases, and 19% (n=14) were grades 3-5. PAH incidence was higher in combination DLL-4-VEGF inhibitor trials versus sole DLL-4 inhibitor trials (16.2% vs 7.9%). Phase 1 and 2 trials displayed similar PAH incidences (11.4% vs 13.0%). Resolution of PAH after drug cessation was reported in 46% of the studies.Conclusions:DLL-4 inhibition treatment for malignancies has demonstrated PAH as a side effect. These results are in accordance with our previous observation that unopposed JAG-1-NOTCH3 signaling, induces pulmonary vascular SMC proliferation and PAH. Discontinuation of DLL-4 inhibitors leads to resolution of disease. Further studies are needed to minimize PAH risk while optimizing oncological benefits of DLL-4 inhibitors before widespread utilization.

Read More

Abstract 4141165: Long-Term Contemporary Outcomes of the Ross Procedure

Circulation, Volume 150, Issue Suppl_1, Page A4141165-A4141165, November 12, 2024. Background:Current evidence supports the use of the Ross procedure (pulmonary autograft) in adults with aortic valve disease.Aims:To examine the ten-year clinical and echocardiographic outcomes following the Ross procedure using a tailored approach.Methods:This prospective cohort included 455 consecutive adults (333 male [73.1%]) with a median age of 50.0 years (IQR, 40.0-57.0) undergoing a Ross procedure at a single center. Patients with aortic aneurysms (37.4%), previous cardiac surgery (15.2%) and active endocarditis (5.7%) were included. The predominant lesion was aortic stenosis (AS) in 379 patients (83.3%) and aortic insufficiency (AI) in 76 patients (16.7%). The study period ranged from February 1, 2011, to December 31, 2019. Primary endpoints were cumulative incidence of any, autograft, or homograft reintervention, and time-related valve function (AI grades 0-4). The secondary endpoint was ten-year survival among Ross patients compared with that in the age- and sex-matched Canadian population. Median clinical follow-up was 6.0 years (maximum 13 years). Follow-up was 90% complete for clinical and 87% complete for echo follow-up.Results:Operative mortality was 0.4% (n=2). Both patients were operated among the first 100 cases. At 10 years, cumulative incidence of any aortic and/or pulmonary reintervention was 5.0% (95% CI, 2.3-9.4%); autograft reintervention 1.5% (0.5-3.4%); and homograft reintervention 3.4% (1.9-5.7%). In patients with preoperative AS, cumulative incidence of autograft reintervention was 1.8% at 10 years (0.6-4.1%), versus 0% in patients with preoperative AI (p=0.6) (Figure 1). At 10 years, cumulative incidence of AI grade >2 was 2.0% (0.9-4.2%), and did not differ between patients with preoperative AS or AI (p=0.9) (Figure 1). Ten-year survival was 96.5% (95% CI, 94.7-98.7%), translating to a relative survival of 100% (99.4-100%) compared to the matched general population.Conclusion:This study demonstrates that using a tailored surgical approach and contemporary perioperative management strategies, the Ross procedure is associated with excellent long-term valve function and freedom from reintervention in an all-comer adult patient population. Moreover, it translates into restored late survival, mimicking the general population. These results further support the notion that, in reference centers, the Ross procedure should be considered in adults needing valve replacement.

Read More

Abstract 4136632: Impact of Postoperative Atrial Fibrillation on Long-term Clinical Outcomes in Patients after Coronary Artery Bypass Grafting

Circulation, Volume 150, Issue Suppl_1, Page A4136632-A4136632, November 12, 2024. Background:The impact of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) on long-term clinical outcomes has not been adequately evaluated yet.Methods:Among consecutive 14927 patients who underwent their first coronary revascularization in the CREDO-Kyoto PCI/CABG Registry Cohort-3 (2011-2013), the study population consisted of 1483 patients who underwent CABG after excluding those with prior AF. POAF was defined as newly documented AF during hospitalization for CABG. The primary outcome measure was all-cause death after discharge. The median clinical follow-up was 5.7 (interquartile range, 4.4-6.6) years.Results:POAF was observed in 337 patients (23%). Multivariable logistic regression analysis indicated that age >=75 years (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.24-2.10; P

Read More