bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143027: Impact of Variants of Uncertain Significance on Mortality, Heart Failure,&Cardiac Arrest in Patients with Single Ventricle Disease
Authors: Mitchell Saige , Foote Henry , Cohen Jennifer , Tallent Sarah , Balint Brittany , Landstrom Andrew
Published: November 2024

Background&Hypothesis:
Single ventricle disease (SVD) is a subtype of congenital heart disease that frequently requires early staged surgical intervention for survival. It is well known that syndromic causes of SVD are associated with worse outcomes. However, the overall effect of variants of uncertain significance (VUSs) found on chromosomal microarray (CMA) has not been explored. We hypothesized that VUSs impart no significant effect on clinical outcomes for patients with SVD when compared to normal chromosomal findings while pathogenic variants have a negative impact on mortality and heart failure.

Objective:
To explore the impact of CMA VUSs on outcomes in patients with SVD.

Methods:
We conducted a review of consecutive patients with SVD born between 1985-2023 with a CMA and treated at our institution. Primary outcomes included heart failure, heart transplantation, cardiac arrest, and mortality. Secondary outcomes included gastrostomy tube (G-tube) insertion, tracheostomy, and extracorporeal membrane oxygenation (ECMO). We controlled for possible confounding factors such as gestational age, birth weight, and age at diagnosis. Rates of primary and secondary outcomes were compared using Fisher’s exact test. Freedom from event curves were generated using a log-rank test for comparison.

Results:
The cohort included 322 consecutive single ventricle patients. The CMA results showed 248 (77.02%) patients having normal CMAs, 42 (13.04%) with VUSs, and 32 (9.94%) with abnormal/pathogenic results. Of those with abnormal CMAs, 22 (68.75%) had a chromosomal abnormality associated with a known genetic syndrome. Analysis using Fisher’s exact test showed lower rates of cardiac arrest and G-tube insertion in VUSs compared to abnormal CMAs (p < 0.05). The one-year survival curve showed higher survival in the normal CMA group compared to the abnormal CMA group (p < 0.05). The cardiac arrest freedom from event curve showed lower event rates in the VUS and normal CMA group compared to the abnormal CMA group (p < 0.05). There was no difference in outcomes between VUSs and normal CMAs.

Conclusions:
Individuals with SVD and a VUS on CMA have survival rates comparable to those with normal CMAs. In contrast, abnormal CMAs are associated with reduced survival. These findings suggest that VUSs and normal CMAs may be less susceptible to cardiac arrest which is a critical complication of SVD.
Abstract 4143037: Prognostic Value of On-Treatment Left Ventricular Global Longitudinal Strain in Elderly Patients with Acute Heart Failure and Preserved Ejection Fraction
Authors: Tseng Chih-Hsueh , Huang Wei Ming , Sung Shih-Hsien
Published: November 2024

Background:
Left ventricular global longitudinal strain (GLS) has been associated with mortality and heart failure hospitalization (HFH) among subjects with chronic heart failure, but not in patients with acute decompensated heart failure (ADHF). The study therefore investigated the prognostic role of GLS in the elder patients with ADHF and preserved left ventricular ejection fraction (LVEF).

Methods:
Patients, aged≥ 65 years hospitalized for ADHF with LVEF ≥ 50% were enrolled in this study. Echocardiography was performed at discharge and after 6-month heart failure treatment. Post-discharge adverse events of cardiovascular death (CVD) and HFH were obtained. Subjects with adverse events during the 6-month treatment were excluded from this analysis.

Results:
Among a total of 514 participants (82.6 ± 13.9 years, 50.6% men), 97 patients encountered CVD or HFH during a mean follow-up duration of 26.8 ± 11.6 months. The eventful subjects had a higher prevalence of diabetes, higher estimated pulmonary pressure, lower hemoglobin levels and was less on treatment with renin-angiotensin system inhibitors. The on-treatment GLS but not pre-discharge GLS was independently associated with adverse events after accounting for age, gender, diabetes, hemoglobin, renal failure, medications and echocardiographic indices [hazard ratio (HR) and 95% confidence intervals (CIs): 1.05, 1.01-1.09]. Additionally, the change in GLS from discharge to 6-month was also associated with adverse clinical outcomes (HR and 95% CIs: 1.05, 1.01-1.09).

Conclusions:
The on-treatment GLS and the change in GLS, but not pre-discharge GLS were independently related to cardiovascular events in the elder patients with HF and preserved LVEF (HFpEF). This study highlights the importance timing to assess GLS among patients with decompensated HFpEF.
Abstract 4143062: Altered Pulmonary Arterial Hemodynamics in Repaired Tetralogy of Fallot Patients Referred for Pulmonary Valve Replacement: A Cross-Sectional 4D Flow Study
Authors: Fujiwara Takashi , Kwong Michael , Fonseca Brian , Stone Matthew , Browne Lorna , Barker Alex
Published: November 2024

Background:
Repaired tetralogy of Fallot (rTOF) patients require pulmonary valve replacement (PVR). Indexed right ventricular systolic/diastolic volumes are currently used to determine PVR timing, but there are recognized limitations. Unique hemodynamic features in the pulmonary arteries of these patients have been found using 4D flow cardiovascular magnetic resonance (CMR), which we hypothesize may inform PVR timing.

Hypothesis:
Hemodynamic alterations in the pulmonary arteries of rTOF patients may inform timing of PVR.

Aims:
To compare pulmonary arterial hemodynamics for rTOF patients who were/were not indicated for PVR after the exams using 4D flow CMR.

Methods:
Clinical 4D flow CMR exams of rTOF patients were accessed retrospectively with IRB approval. Patients were classified into two groups depending on whether they underwent PVR after the CMR exam. Age-matched controls’ 4D flow data were also included. After pre-processing of 4D flow, the right ventricular outflow tract, main, left and right pulmonary arteries (RVOT, MPA, LPA and RPA) were manually segmented from phase-contrast magnetic resonance angiography. In addition to basic flow metrics such as regurgitant fraction, systolic and diastolic averages of helicity, vorticity, and viscous energy loss were computed for the four subdomains using an automated pipeline (Fig.1). Indexed end-systolic/diastolic right ventricular volumes were obtained from clinical CMR reports. P<0.05 was considered statistically significant.

Results:
Eighteen controls (age, 14.9 [11.7-17.0] years) and 21 rTOF patients, consisting of 8 without PVR (noPVR; age, 14.7 [9.6-23.4] years) and 13 indicated for PVR after the exam (PVR; age, 16.1 [8.7 -20.3 years]; days between CMR and PVR, 134 [59.5 – 189.3] days), were included. The PVR group had significantly larger indexed right ventricular volume than the noPVR group (P=0.002; Table 1). Regurgitant fraction and diastolic vorticity at the LPA were significantly larger in the PVR group (P=0.007 for regurgitant fraction; P=0.02 for vorticity; Fig.2AB). Although not statistically significant, diastolic helicity at the MPA showed borderline significance (P=0.05; Fig.2C).

Conclusion:
In addition to right ventricular dilatation and larger regurgitant fraction, patients indicated for PVR had larger vorticity in the LPA. This preliminary result could be used for future longitudinal study to determine hemodynamic markers that inform PVR timing. A larger cohort is under evaluation.
Abstract 4143067: Enhanced Mevalonate Pathway Through Laminar Flow-Induced DDIAS/ACLY Complex Supports Antioxidant Pathways and Angiogenesis Post-Hindlimb Ischemia
Authors: Chau Khanh , Kotla Sivareddy , Samanthapudi Venkata Subrahman K , Lee Jonghae , Osborn Abigail , Hoang Oanh , Mejia Gilbert , Abe Junichi , LE NHAT TU
Published: November 2024

Background:
Atherogenesis often develops in regions with disturbed blood flow (d-flow), involving increased ERK5 and p53 SUMOylation due to SENP2 T368 phosphorylation, leading to increased ERK5 and p53 SUMOylation, contributing to endothelial cell (EC) activation. Conversely, laminar flow (l-flow) induces SENP2 S344 phosphorylation, reducing ERK5 and p53 SUMOylation, thereby suppressing EC activation. The presence of senescent ECs in atherosclerotic plaques suggests that d-flow-induced EC senescence may contribute to atherogenesis, possibly due to metabolic changes. EC glycolysis is crucial for NO production and atheroprotection, however, it is inhibited by l-flow, indicating that l-flow protective effects extend beyond glycolysis.

Methods:
In ECs from wild-type mice exposed to l-flow, the expression of DDIAS increases, regulated by SENP2 S344 phosphorylation. DDIAS interacts with ACLY, a key regulator of fatty acid metabolism and vascular function. We performed LC-MS and IC-MS analyses on ECs with DDIAS knocked down or control siRNA exposed to l-flow, using
13
C
2
-gucose or
13
C
5
-glutamine to trace metabolic changes. HMG-CoA, acetyl-CoA, and CoQ levels were measured using LC-MS and triple quadrupole LC-MS/MS.

Results:
L-flow enhances glycolysis and glutaminolysis, significantly increasing TCA cycle intermediates through upregulated glutamine pathways. DDIAS expression and its interaction with ACLY are also increased by l-flow. Without DDIAS, the ACLY-mediated mevalonate pathway is inhibited, reducing l-flow-induced antioxidant mechanisms. Thus, the DDIAS-ACLY complex is crucial for the antioxidant response triggered by L-flow, which is essential for supporting angiogenesis after hindlimb ischemia. L-flow-induced increases in HMG-CoA and CoQ are inhibited by DDIAS depletion, highlighting the importance of DDIAS in maintaining the balance of metabolic and antioxidant pathways under L-flow.
We are investigating the role of DDIAS-ACLY complex on l-flow-mediated upregulation of glycolysis and glutaminolysis.

Conclusion:
DDIAS plays a key role in mediating l-flow atheroprotective effect by directly interacting with and activating ACLY, essential for the mevalonate pathway and subsequent HMG-CoA and CoQ biosynthesis. Under l-flow conditions, ECs preferentially utilize glutamine over glucose for TCA cycle intermediates, underscoring the importance of the DDIAS-ACLY complex in supporting EC protection and function through enhanced metabolic pathways.
Abstract 4143069: Serum Glucocorticoid Regulated Kinase 1 (SGK-1) Inhibitor Reduced Hypertension in a Salt-Sensitive Hypertension Model of Heart Failure with Preserved Ejection Fraction
Authors: Pradhananga Sabindra , Shilova Olga , Srinivasan Dinesh , Senese Peter , Gralinski Michael , Zammit Melissa , Sager Philip , Das Saumya
Published: November 2024

Background:
Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex clinical syndrome marked by multiple cardiac and extracardiac pathophysiological alterations. Despite accounting for 50% of HF diagnoses, treatment options for HFpEF remain limited. Serum and glucocorticoid regulated kinase 1 (SGK1), a PI3-kinase-dependent kinase, is demonstrated to play a role in HF and atrial fibrillation.

Hypothesis:
Based on the role of SGK1 in renal sodium homeostasis, inflammation, and fibrosis, we hypothesized that SGK1 inhibition would prevent the progression of HFpEF. This hypothesis was tested by assessing the efficacy of a novel and potent SGK1 inhibitor, SGK1-I, in a rat model of HFpEF.

Methods:
Forty Dahl salt sensitive (Dahl SS) rats were fed low salt diet (LSD, 0.3% NaCl) or high salt diet (HSD, 8% NaCl) for a total of 12 weeks. After 6 weeks, rats were treated with vehicle or SGK1-I (10 or 25 mg/kg/day) via oral gavage for an additional 6 weeks. Intracardiac hemodynamics and cardiac structure and function were assayed using pressure volume loop and echocardiography respectively. BP and cardiac structure data from 4-6 animals/group are discussed.

Results:
Dahl SS rats fed with HSD exhibited increased systolic arterial pressure (SAP; LSD: 85±9.8, HSD: 132±29.4 mmHg, p =0.01) and diastolic arterial blood pressure (DAP; LSD: 152±12.5, HSD: 202.8±27.0 mmHg, p = 0.03); SGK1-I reduced the HFD SAP (10 mg/kg/day: 190±37 mmHg, p=0.13 and 25 mg/kg/day: 164±5 mmHg, p=0.93) and DAP (10 mg/kg/day: 122±29 mmHg, p=0.07 and 25 mg/kg/day: 99±6 mmHg, p=0.84) in a dose dependent manner to the LSD levels. The high dose of SGK1-I also reduced HSD-induced alteration in left ventricular (LV) morphology, including posterior wall thickness (HSD: 2.38±0.32 mm, SGK1-I: 2.21±0.24 mm, p< 0.05) and improved ratio of LV+septum mass to tibia length (HSD: 26.53±0.00 mg/mm, SGK1-I: 25.18±0.00 mg/mm, p<0.05). The dose dependent reduction of left ventricle pressure development and maximal pressure in HSD rats administered with SGK1-I suggests protection is due to alleviation of hypertension induced pressure overload in the heart.

Conclusion:
Data analyzed to date suggest SGK1-I administration reduces elevations in blood pressure and subsequent alteration in LV morphology in Dahl SS rats fed with HSD. These data support the need for additional preclinical studies to explore the use of SGK1 inhibition as a promising target for the treatment of HFpEF associated with hypertension.
Abstract 4143083: Cardiomyopathy in Pregnancy Complicated by Loeys-Dietz Syndrome
Authors: Mei Pristine , McGrath Lidija
Published: November 2024

Case Description:
A 28-year-old G2P1 woman presented at 27 weeks gestation with progressive dyspnea and lower extremity edema. She was found to have atrial fibrillation and flutter with RVR. Initial TTE revealed severely dilated left ventricle (LV) with reduced systolic function (EF 20-25%) (Figure 1). She remained in flutter despite diuresis, rate control with metoprolol and digoxin, cardioversion, and ablation. Initiation of guideline-directed medical therapy was limited by hypotension and pregnancy. She underwent a cesarean section at 32 weeks given ongoing arrhythmia and heart failure symptoms. Skin fragility and poor uterine tone were noted intraoperatively. This, in addition to her exam findings of arachnodactyly and hypertelorism, prompted genetic testing, which was positive for
SMAD3
mutation consistent with Loeys-Dietz syndrome (LDS) type 3. Following delivery, spironolactone and enalapril were added in keeping with breastfeeding compatibility. Her arrhythmia burden continued to lessen. Repeat TTE showed EF of 35-40% and normal LV size. MRA of head to pelvis was notable for mild dilation of intrarenal abdominal aorta (2.5 cm) with no other vascular abnormalities.

Discussion:
Loeys-Dietz syndrome is an inherited connective tissue disorder caused by mutations in
TGFBR
1/2,
TGFB
2/3, and
SMAD
3. It is characterized by multisystem involvement with cardiovascular, craniofacial, skeletal, and cutaneous features. Cardiomyopathy and arrhythmia have been described in a small number of cases. This case represents a rare manifestation of LDS diagnosed during pregnancy where hemodynamic changes likely precipitated development of symptoms and intraoperative findings, which informed additional testing and led to the diagnosis. More commonly, LDS presents with widespread arterial and aortic aneurysms that carry a high risk of dissection. Aortic dissection represents a major cause of early mortality in LDS often requiring intervention at a younger age. Complete vascular imaging is recommended at initial diagnosis, with regular surveillance thereafter. Beta blockers and angiotensin receptor antagonists are used in slowing aortic dilatation; cardiomyopathy and arrhythmias should be treated according to established guidelines.
Abstract 4143140: Pregnancy Termination or Perinatal Hospice due to Fetal Congenital Heart Defects: A Qualitative Analysis
Authors: Knowles Grace , Madden Diana , Barrera Leonardo , Fry Jessica , Grobman William , Henner Natalia , Patel Angira , patel sheetal , Yee Lynn , Woo Joyce
Published: November 2024

Background:
For some individuals, antenatal diagnosis of a congenital heart defect (CHD) allows alternative options to cardiac surgery: pregnancy termination or perinatal hospice care. Understanding drivers of decision-making for these two non-surgical options is critical to guide patient-centered counseling practices. We aimed to explore experiences and decision-making among individuals who chose termination or perinatal hospice care after diagnosis of a fetal CHD.

Methods:
This was a qualitative analysis of semi-structured, 1:1 interviews with birthing individuals or their partners from a purposive sample of those who experienced termination or perinatal hospice after receiving multidisciplinary counseling for severe fetal CHD at Lurie Children’s between 2019-2022. The interview guide was comprised of open-ended questions addressing counseling experiences, decision making, and for relevant participants, postnatal experience with perinatal hospice care. The guide was designed by fetal cardiologists, maternal-fetal medicine specialists, neonatologists, palliative care specialists, qualitative researchers, an ethicist, and two parent advisors. Interviews (60-90 minutes) were professionally transcribed and analyzed using Dedoose software. Thematic analysis was conducted with an inductive approach.

Results:
In total, 20 pregnant individuals and their partners met inclusion criteria and were asked to participate. Of these, 10 completed interviews, 9 carried fetuses with single ventricle disease, 2 experienced perinatal hospice care, and 8 identified as non-Hispanic White ethnicity/race. Themes included variability in antenatal counseling, value for reproductive justice, life factors considered in decision-making, and successful aspects of perinatal hospice (Table).

Conclusion:
Among individuals who experienced termination or perinatal hospice due to fetal CHD, there is significant variability in the experiences with counseling. Yet, there is shared value for provider support, consideration for life factors in decision-making, and reproductive autonomy. Understanding both the variability and shared themes is key to optimize and standardize counseling practices for fetal CHD.
Abstract 4143142: Lost to Follow Up: A Rare Case of Malonyl-CoA Decarboxylase Deficiency Induced Cardiomyopathy in an Adult Spanish Speaking Hispanic Male
Authors: Iniguez Reniell , Quaggin-Smith Jessica , Hale Sarah , Wilcox Jane
Published: November 2024

Introduction:
Malonyl-CoA decarboxylase deficiency (MLYCDD) is a rare inherited metabolic disorder with multi-organ involvement, causing cognitive impairment, cardiomyopathy, seizures, hypotonia, and acidosis. Variants in MLYCCD, the gene for malonyl-CoA decarboxylase, disrupt long chain fatty acid synthesis in cardiac tissue. Prevalence is estimated to be less than 1 in 1,000,000, with cardiomyopathy being the leading cause of morbidity and mortality. Less than 40 cases have been documented, the majority of which detail newborns. No guidelines exist for treatment. A high-carbohydrate, low-fat diet, and levocarnitine reportedly improve cardiac function.

Presentation:
A 30-year-old Spanish-speaking male with MLYCDD, with resultant heart failure with reduced ejection fraction (EF) and cognitive delay, presented to a community hospital with malaise. He was diagnosed at age 9 and followed with an interdisciplinary team, receiving care in Spanish and English since diagnosis. His treatment consisted of levocarnitine and dietary restrictions that had led to cardiac recovery. At 24, his doctor retired, his insurance changed, and he was lost to follow-up, leading to dietary liberalization. On presentation, he was diagnosed with pneumonia complicated by atrial fibrillation (AF). AF was treated with a diltiazem infusion, resulting in cardiogenic shock with an EF of 15% from 39%. He was transferred to an academic center where diltiazem was stopped, inotropes started, and impella placed. He started enteral nutrition with liquid protein, dextrose infusion, medium-chain triglyceride (MCT) oil, and levocarnitine, along with supportive care for pneumonia. Given persistent shock he was transferred to our center for advanced therapies evaluation. Notable changes included replacing MCT oil with triheptanoin and stopping the dextrose infusion. A repeat echocardiogram showed recovery of EF to 40%

Conclusions:
MLYCDD exhibits a range of phenotypes, with limited data on long-term outcomes. This presentation is atypical: an adult with cardiomyopathy diagnosed in adolescence, successfully treated, who decompensated after stopping a modified diet in the setting of pneumonia and diltiazem. This case offers several clinical insights: (1) Restrictive diets with levocarnitine supplementation are instrumental in treating MLYCDD. (2) Avoid diltiazem in heart failure to prevent iatrogenic shock. (3) Language-concordant care ensures patients understanding and supports seamless care transitions.
Abstract 4143164: Autoimmunity and Sex Inform Clinical Outcomes of Non-Aortic Arterial Dissections
Authors: Gonzalez Moret Yurilu , Chacin Suarez Audry , Musri M. Carolina , Yanamandala Mounica , Lo Kevin , Loscalzo Joseph , Gerhard-Herman Marie , Pandey Arvind
Published: November 2024

Background:
Non-aortic arterial dissections (NAAD) are increasingly diagnosed on imaging but natural history of disease in women and men is poorly understood, and long-term outcomes are still not well-defined. NAAD pathobiology is broadly subdivided as either rheumatologic or non-rheumatologic, but whether this binary classification is relevant for clinical outcomes is not clear.

Methods:
Utilizing the TriNetX Research Collaborative Network containing nearly 90 million deidentified electronic health records, patients aged 18 years or older diagnosed with NAAD between January 1, 2014 to May 8, 2024 were stratified into two cohorts based on presence or absence of a diagnosed rheumatologic condition. Patients were identified using ICD-9/10 codes to include any code for a large or medium vessel arterial dissection and/or rheumatologic condition; patients with aortic dissection codes were excluded. Following propensity score matching for covariates, groups were analyzed for all-cause mortality and major adverse cardiovascular events (MACE) (stroke, cardiac arrest, acute myocardial infarction, heart failure) after 1 year and 5 years using Kaplan-Meier survival analysis with log-rank testing and Cox proportional hazard model.

Results:
A total of 64,984 patients were identified to have an ICD-9/10 code for a NAAD; 60,196 had no associated rheumatologic condition and 4,698 had a co-morbid rheumatologic ICD-9/10 code. Prior to propensity matching, NAAD patients with rheumatologic conditions were more likely to be older (59.6 vs 54.5 years), female (63% vs. 47%), and have a greater prevalence of cardiovascular risk factors (p < 0.001 for all). After propensity matching, NAAD patients with rheumatologic conditions had higher all-cause mortality at 1 year (hazard ratio [HR] with 95% confidence intervals: 1.34 [1.12-1.60]) and 5 years (HR: 1.21 [1.07-1.38]) compared to non-rheumatologic NAAD patients. Non-rheumatologic dissection patients exhibited sex-biased outcomes, with mortality (1-year HR: 1.26 [1.17-1.35], 5-year HR: 1.25 [1.18-1.33]), MACE (5-year HR: 1.08 [1.01-1.15]), and need for vascular procedures (2.5% versus 2.05%, p < 0.001) more likely to occur in men than women; conversely, rheumatologic dissection patients did not show sex-based differences.

Conclusions:
The presence of co-morbid rheumatologic conditions is associated with greater mortality in patients with NAAD. Sex is an important modifier of clinical outcomes in non-rheumatologic dissection patients.
Abstract 4143171: Pattern of Disease Progression in ATTR-CM Patients Treated with Tafamidis: An Observational Study
Authors: Bampatsias Dimitrios , Wardhere Abdirahman , Zeldin Lawrence , Mirabal Alfonsina , Weinsaft Ariel , Smiley Dia , Teruya Sergio , Maurer Mathew
Published: November 2024

Background:
Consensus on a definition of disease progression in transthyretin amyloid cardiomyopathy (ATTR-CM) is lacking. Recent data showed that among a large cohort 50% of patients progressed as defined by either N-terminal pro-B type natriuretic peptide (Nt-proBNP) increase of 700 pg/ml AND 30% or increase of oral diuretics (ODI) after 1 year. However, most of the patients were not on disease modifying treatment (DMT).

Aim:
To describe the pattern of progression at 1 year in patients with ATTR-CM on tafamidis, the only approved drug for ATTR-CM.

Methods:
Patients diagnosed with ATTR-CM at Columbia University and treated with tafamidis after 2018 were enrolled in the study assuming they survived a year to measure disease progression and had data available at follow-up. A total of 16 patients died before the 1-year follow-up and were excluded from the study. Disease progression was defined as: increase in Nt-proBNP>700 pg/mL and >30% from baseline, ODI or increases in both compared to baseline. Survival analysis was done using Kaplan Meier curves and Cox regression adjusted for age and disease severity by National Amyloidosis Center stage.

Results:
A total of 157 patients were enrolled, with 62 (39.5%) having disease progression at 1-year. Of these 62 patients, 51 met one progression criterion (34 patients had ODI and 17 had NtproBNP increase), with 11 having both criteria of disease progression at 1 year. Survival analysis revealed a significantly increased risk for all-cause mortality during follow-up in patients with disease progression at 1-year (HR=2.13, 95%CI:1.04-4.35, p=0.03, Figure).

Conclusion:
The recently proposed criteria for disease progression performed well in a cohort of patients on DMT, which may reduce the number of patients progressing at 1 year.
Abstract 4143193: Integrating Clinical, Genetic, and Electrocardiogram-Based Artificial Intelligence to Estimate Risk of Incident Atrial Fibrillation
Authors: Kany Shinwan , Rämö Joel , Friedman Samuel , Weng Lu-Chen , Kim Min Seo , Fahed Akl , Lubitz Steven , Philippakis Anthony , Maddah Mahnaz , Ellinor Patrick , Khurshid Shaan
Published: November 2024

Background:
Atrial fibrillation (AF) risk estimation is feasible using clinical factors, inherited predisposition, and artificial intelligence (AI)-enabled electrocardiogram (ECG) analysis. Whether integrating these distinct risk signals improves AF risk estimation is unknown.

Methods:
In the UK Biobank prospective cohort study, we estimated AF risk using three models derived from external populations: the well-validated Cohorts for Aging in Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) clinical score, a published AI-enabled ECG-based AF risk model (ECG-AI), and a 1113667-variant AF polygenic risk score (PRS). We estimated discrimination of 5-year incident AF using time-dependent area under the receiver operating characteristic (AUROC) and average precision (AP).

Results:
Among 49,293 individuals (mean age 65±8 years, 52% women), 825 (2.4%) developed AF within 5 years. Using single models, discrimination of 5-year incident AF was higher using ECG-AI (AUROC 0.705 [95%CI 0.686-0.724]; AP 0.085 [0.071-0.11]) and CHARGE-AF (AUROC 0.785 [0.769-0.801]; AP 0.053 [0.048-0.061]) versus the PRS (AUROC 0.618, [0.598-0.639]; AP 0.038 [0.028-0.045]). The best performing two component model was CHARGE-AF+ECG-AI (AUROC 0.802 [0.786-0.818]; AP 0.098 [0.081-0.13]), with further improvement observed with inclusion of all components (“Total-AF”, AUROC 0.817 [0.802-0.832]; AP 0.11 [0.091-0.15], p<0.01 vs CHARGE-AF+ECG-AI). Using Total-AF, individuals at high AF risk (i.e., 5-year predicted AF risk >2.5%) had a 5-year cumulative incidence of AF of 5.83% (5.33-6.32). At the same threshold, the 5-year cumulative incidence of AF was progressively higher according to the number of models predicting high risk (zero: 0.67% [0.51-0.84], one: 1.48% [1.28-1.69], two: 4.48% [3.99-4.98]; three: 11.06% [9.48-12.61]. Total-AF achieved favorable net reclassification improvement compared to both CHARGE-AF+ECG-AI (0.039 [0.015-0.066]) and CHARGE-AF+PRS (0.033 [0.0082-0.059]).

Conclusions:
Integration of clinical, genetic, and AI-derived risk signals improves discrimination of 5-year AF risk over individual components. Models such as Total-AF have potential to improve the prioritization of individuals for AF screening.
Abstract 4143294: Pacing Towards a Better Future: A Case of Tailored Pacemaker Programming in HFrEF
Authors: Mango Lana , Younis Ahmad , Rizik Aseel , AbuHawas Dania , Turk Ahmad
Published: November 2024

Introduction:
Cardiac pacing devices, including Permanent Pacemakers (PPM) and Implanted Cardioverter Defibrillators (ICD), are essential in managing various cardiac conditions. Exercise capacity in patients hinges on both cardiac function enhancement and an appropriate chronotropic response. This case report underscores the strategic use of Cardiopulmonary Exercise Testing (CPET) to determine the activation of the Rate Response to Exercise (RRE) function in a patient with Heart Failure with reduced ejection fraction (HFrEF).

Case Report:
Our patient is a 64-year-old male with HFrEF due to hypertensive heart disease and ICD placement. He was undergoing therapy optimization at our advanced heart diseases clinic. Initially presenting with poor functional capacity, his condition improved significantly with ongoing therapy adjustments, as reflected by his KCCQ scores. This improvement enabled a comprehensive assessment using CPET. The initial CPET trial revealed moderately reduced exercise capacity and an absent chronotropic response, with a heart rate at 65 bpm and a peak VO2 of 67% predicted, categorizing him as Weber Class B. Based on these findings, we activated the RRE function and conducted a follow-up CPET. The re-evaluation demonstrated notable improvements: extended exercise duration post-anaerobic threshold, a peak VO2 of 72% predicted, and an upgraded Weber Class A status.

Summary:
This case exemplifies how tailored programming of pacing devices can significantly enhance exercise capacity in HF patients. Activating the RRE function in the patient's PPM led to marked improvements in exercise capacity and prognostic indicators derived from CPET parameters, corroborating the limited existing data on this approach. Although specific guidelines are lacking, our findings highlight the utility of CPET in customizing PPM settings, particularly for HFrEF patients. This report underscores the importance of individualized treatment and invites further research into optimizing device settings to maximize patient outcomes. Leveraging CPET in routine clinical practice could revolutionize heart failure management, offering a precise and patient-centric approach.
Abstract 4143305: Risk Factors for Adverse Outcomes in a Fontan Population
Authors: Licitra Giancarlo , Ivey Lindsey , Raskind-Hood Cheryl , Rodriguez Fred , Guo Yuting , SARKER ABEED , Book Wendy
Published: November 2024

Introduction/Background:
Improved survival following Fontan surgery has been tempered by Fontan failure. Heterogenous multi-organ complications varying over time have limited study of Fontan failure. We sought to identify complications associated with hospitalization.

Methods/Approach:
A retrospective cohort of 735 pediatric and adult Fontan patients were identified from two healthcare systems (median age 7yrs, IQR 14, 57.4% male, 41.0% black). The deduplicated cohort was linked to 2010-2019 encounters from both healthcare systems (one pediatric, one adult) and to death certificates to capture vital status. ICD-9-CM and ICD-10-CM codes were mapped by clinicians to capture variables of interest. Bivariate analyses were conducted to examine select covariates by the composite outcome which includes heart transplant, hepatocellular carcinoma (HCC) and death during the surveillance period; group differences were examined using chi-square, Fisher exact and independent t-tests. Negative binomial regression evaluated the association between select characteristics and hospitalization rates with adjustment.

Results/Data:
Of 735 Fontan patients,11.6% experienced the primary outcomes (median age 14yrs, IQR 17). Characteristics significantly associated with the composite outcome included older age, dysrhythmia, liver disease, cyanosis and heart failure (Table 1). Modeling showed increased rates of hospitalization for children with dysrhythmia (RR=1.43, 95%CI 1.13-1.80) and cyanosis (RR=2.32, 95%CI 1.78-3.03) adjusting for potential confounders (Table 2). This association remained for adults, however, after adjustment, the association of cyanosis and hospitalization rate was attenuated.

Conclusion:
Fontan patients with dysrhythmia, liver disease, cyanosis and heart failure are at an increased risk for heart transplant, HCC, and death, and have higher hospitalization rates. Incorporation of these factors into the definition of Fontan failure may help early identification and intervention.
Abstract 4143317: Left Atrial Reservoir Phase Duration and Long-Term Survival After Cardiac Resynchronization Therapy
Authors: Hammersboen Lars-Egil , Aalen John , Puvrez Alexis , Larsen Camilla , Remme Espen , Kongsgaard Erik , Duchenne Jurgen , Galli Elena , Khan Faraz , Sletten Ole Jakob , Penicka Martin , Donal Erwan , Voigt Jens-Uwe , Smiseth Otto , Stugaard Marie
Published: November 2024

Background:
Recent observations suggest that residual left atrial (LA) dyssynchrony after cardiac resynchronization therapy (CRT) may have prognostic significance. Since LA dyssynchrony implies prolongation of the LA reservoir phase, measuring the duration of the LA reservoir phase should offer similar prognostic information.

Purpose:
To investigate the impact of LA reservoir phase duration on long-term survival after CRT.

Methods:
In a recent prospective multicenter study of 168 patients, LA strain was measured by speckle-tracking echocardiography before and 7±1 months after CRT. LA reservoir strain was measured as the difference between peak and minimum global strain during the atrial cycle and LA reservoir phase duration as the time from onset shortening in the left ventricle to peak LA reservoir strain. Since LA reservoir strain <18% is associated with elevated LV filling pressure, we used 18% as cutoff and for LA reservoir phase duration 516 ms in accordance with a Receiver Operating Curve. All-cause mortality was used as clinical endpoint during follow-up.

Results:
After 6.0±1.8 years follow-up, 35 (21%) patients had died. LA reservoir strain ≥18% after CRT was associated with favorable long-term survival (HR: 0.51, 95% CI: 0.26–0.98) (upper panel in the Figure). LA reservoir phase duration was not independently associated with survival. However, when used in patients with LA reservoir strain ≥18% after CRT, LA reservoir phase duration ≤516 ms identified patients with particularly excellent long-term survival (HR: 0.18, 95% CI: 0.05–0.63 vs patients with reservoir strain ≥18% and LA reservoir phase duration >516 ms) (lower panel in the Figure). Patients with preserved LA reservoir strain but prolonged LA reservoir phase duration had similar outcome as patients with reduced LA reservoir strain (HR 1.10, 95% CI: 0.49–2.51).

Conclusions:
LA reservoir strain ≥18% combined with reservoir phase duration ≤516 ms is associated with excellent long-term survival after CRT. Prolonged reservoir phase duration is linked to adverse long-term outcomes in patients with preserved LA reservoir strain. Therefore, reservoir phase duration provides added value for risk prediction after CRT that may be clinically important.
Abstract 4143335: Prenatal Dibutyl Phthalate Exposure Dysregulates Fetal-Placental Vascular Function and Spatial Transcriptomic Profile
Authors: Yang Xinran , Mamidi Aastha , Chavez Andre , Kadlec Dilen , Craig Zelieann , Zhou Chi
Published: November 2024

Introduction:
Fetal vascular dysfunction during pregnancy has long-term adverse effects on the cardiovascular health of the offspring. Prenatal exposure to dibutyl phthalate (DBP), is associated with adverse pregnancy/fetal outcomes and cardiovascular diseases in the offspring. To date, the impact of DBP exposure on fetal vascular function during pregnancies is unclear.

Hypothesis:
Environmentally relevant low-dosage DBP exposure during pregnancy differentially dysregulates fetal placental vascular function.

Methods:
Adult female CD-1 mice (10-12wks) were treated with vehicle (CT) or DBP at 0.1 μg/kg/day (DBP0.1) daily 30days before pregnancy through gestational day (GD) 18.5. Fetal-placental blood flow was measured non-invasively using a high-frequency ultrasound (Vevo3100, n=6-8dams/group). Spatial transcriptomic sequencing was performed using Visium (10xGenomics)&NovaSeq (Illumina) with GD18.5 placentas (n=3/fetal sex/group). Bioinformatic analysis was performed with SpaceRanger, Suerat and IPA software. Spatial gene expression validation and lipid disposition were performed with IHC and Oil Red O staining (n=6-8 litter/group).

Results:
DBP0.1 increased the fetal umbilical-placental velocity time integral (7.9±0.6mm vs. 6.5±0.8mm) at GD18.5. DBP0.1 decreased placental efficiency with more dramatic changes seen in female fetuses. Spatial transcriptomic analysis obtained 20,161 spatial-linked units from placentas from CT and DBP0.1 placentas (median: 140k reads&6,174 genes per unit). Bioinformatic analysis revealed 15 distinct clusters of units that were annotated to 10 different cell types (based on gene expression profiles) that precisely mapped to corresponding placental morphological structures. We identified vascular endothelial cells (ECs-1 [microvasculature]&ECs-2 [larger vasculature]) 2 populations in the fetal placental labyrinth. Pseudo-bulk analysis showed that DBP0.1 dysregulated 40 and 6 genes in ECs-1 from female and male placentas, respectively, but did not affect gene expression in ECs-2. Further, DBP0.1 dysregulates lipid metabolism-associated pathways only in female but not in male ECs-1. This is consistent with our Oil Red O data showing prenatal DBP0.1 exposure significantly decreased lipid disposition in the fetal labyrinth of female, but not in male placentas.

Conclusions:
Prenatal DBP0.1 exposure dysregulates fetal-placental blood flow velocity, placental efficiency, placental spatial transcriptomic profile and lipid disposition.
Abstract 4143351: Early experience with percutaneous insertion of pulmonary blood flow restrictors to allow deferral of Norwood surgery
Authors: Prasanna Anagha , Fox Jeremy , Tannous Paul , Ohalloran Conor , Eltayeb Osama , Monge Michael , Nugent Alan , Allen Kiona , Berger Stuart , Winlaw David
Published: November 2024

Deferral of the Stage 1 Norwood Palliation (S1P) for infants with hypoplastic left heart syndrome and other high-risk features is sometimes accomplished using a hybrid approach involving external pulmonary artery (PA) banding. Recently, percutaneous restriction of pulmonary blood flow has been accomplished with off-label modification of microvascular plugs (Medtronic) to delay surgical intervention.

This single-center, retrospective case series examines outcomes associated with PA flow restrictors in patients at both high and standard-risk for S1P. High-risk criteria included prematurity, birth weight less than 2.5 kg, moderate or greater atrioventricular valve regurgitation, highly restrictive atrial septum, and genetic comorbidities. Primary outcomes included death, need for extracorporeal membrane oxygenation (ECMO), PA re-intervention, and variation from expected pathway post bidirectional Glenn (BDG), which includes prolonged intubation (>24 hours), persistent hypoxia (saturation <75%), or prolonged hospital length of stay (>14 days).

From September 2023 to May 2024, bilateral PA flow restrictors were placed in 9 S1P-eligible neonates (Table 1). Two patients died with flow restrictors before S1P. One patient developed progressive heart failure and underwent a successful heart transplant after having PA flow restrictors in place for 200 days. The remaining 6 patients had a S1P operation with removal of flow restrictors and PA plasty at a median of 21 days post insertion and 25 days of life. Three patients required PA stents between S1P and BDG. Four patients have progressed to Glenn, all of whom had courses that significantly varied from the expected pathway, including 2 who required early PA stenting, 4 who had prolonged hospital stays, and 1 patient who died of multiorgan failure due to failed BDG circulation.

Flow restrictors can delay surgical S1P in high-risk patients, allowing for evaluation of additional comorbidities. They are a useful adjunct to the management of high-risk patients prior to S1P. However, their use appears to be associated with an important rate of PA complications, resulting in significant variation from the expected clinical course and may impact later quality of BDG circulation.
Abstract 4143354: Novel Methods Improve Assessment of Virtual Reality’s Impact on Physician Mental Models During Pre-Surgical Planning
Authors: Bethke Eliot , Bramlet Matthew , Amos Jennifer , Evans James , Sutton Bradley
Published: November 2024

Background:
Virtual Reality (VR) has found numerous applications in healthcare, including 3D presentation of patient anatomy modeled from traditional medical imaging. While individual VR systems have been evaluated for their utility in pre-surgical planning, there remains a gap in understanding of the impact VR has on physicians’ mental models. VR is often assessed on performance criteria, omitting relevant perspectives of the physician’s experience.

Research Questions:
We sought to explore the following: 1) How does VR affect physicians’ perceptions of complex congenital heart cases, and 2) What strategies do physicians employ while exploring patient anatomy in VR.

Goals and Aims:
The aim of this study was to analyze how mental models change after reviewing anatomy in VR, and to describe common patterns of behavior in VR which provide deeper insight into the complex task of pre-surgical planning.

Methods:
We deployed a novel methodology of undirected think-aloud sessions in VR which we anchored to pre and post-session questionnaires based on the NASA Task Load Index. VR sessions were recorded in first-person view and were qualitatively analyzed by five independent coders using a grounded theory approach where codes emerged from the data. Iterative refinement of codes led to identification of multiple patterns of behavior which were summarized thematically. Pre and post-session surveys were analyzed statistically.

Results:
10 VR sessions were captured from 3 physicians totaling 2.5 hours of recordings. Physician confidence in their understanding of the anatomy increased from a mean of 4/5 before VR to 5/5 after (p=0.012). Themes emerging from VR sessions included: 1) Exploration of the 3D environment led to confirmation of understanding and complex decision making, 2) Emotions expressed in VR reflected strengths and weaknesses of the VR tool, and 3) Confidence may mask complex decision making crucial to the surgical planning process. Reported mental, physical, and time demands of VR all remained low (<3/10 median) with high accomplishment of goals (10/10 median).

Conclusion:
Eliciting rich descriptions of physician perspectives of patient anatomy in VR provides a more detailed glimpse at the decision making and exploration which helps to refine mental models during pre-surgical planning. The 3D VR environment helps enable exploration of the anatomy which in turn leads to complex decision making and refinement of understanding of the case before surgery.
Abstract 4143355: Association of Elevated Serum Lipoprotein(a) with New-Onset Atrial Fibrillation: A Retrospective Study of 108930 Patients
Authors: Kamel Moaz , Awad Kamal , Mahmoud Ahmed K. , FARINA JUAN , Scalia Isabel , Pereyra Milagros , Abbas Mohammed Tiseer , Baba Nima , Ayoub Chadi , Arsanjani Reza
Published: November 2024

Background:
Atrial fibrillation (AF), the most common clinically managed cardiac arrhythmia, is known to increase the risk of heart failure, stroke, and mortality. Lipoprotein(a) [Lp(a)], a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), also plays a role in cardiovascular health. However, the influence of Lp(a) on the development of AF, independent of its association with ASCVD, remains unclear.

Hypothesis:
Elevated Lp(a) may be associated with increased risk of new-onset AF.

Methods:
A retrospective study was conducted on patients from the three Mayo Clinic sites who had their Lp(a) levels measured and had no prior history of AF. Patients were categorized into two groups based on their serum Lp(a) concentrations: high Lp(a) (≥50 mg/dL) and low Lp(a) (<50 mg/dL). New AF diagnoses were identified during the follow-up period. Survival probabilities between the two Lp(a) groups were compared using the Kaplan–Meier curve and the Log-Rank test. Cox regression analyses, both univariable and multivariable, were performed to evaluate established risk factors and compare the risk of new-onset AF between the high and low Lp(a) groups.

Results:
A total of 108,930 patients were included (median age: 55 years, 58% males), with a follow-up duration for up to 10 years. Incident AF was detected in 8432 (7.7%) patients. Median serum levels of Lp(a) were significantly higher in patients with AF versus non-AF patients: 15 (IQR 43) vs. 12 (IQR 34) mg/dL, p<0.001. The percentage of patients having elevated Lp(a) was significantly higher in the AF group versus non-AF group: 2119 (25%) vs 21151 (21%), p<0.001. Survival probability for new-onset AF was significantly lower in patients with elevated Lp(a) compared with those with low Lp(a) (log rank p<0.001, Figure 1). In the univariate analysis, high Lp(a) levels were associated with a 17% increase in the risk of AF (HR = 1.17, 95% CIs: 1.12 to 1.23). The multivariate analysis adjusted for well-established risk factors for AF showed a less strong but still significant association, with a 10% increase in AF risk (HR = 1.10, 95% CI: 1.05 to 1.15).

Conclusion:
Our study suggests that elevated Lp(a) (≥50 mg/dL) seems to be an independent risk factor for new-onset AF. Future prospective studies are still warranted to validate our results.