bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4142996: Controlled LDL levels can Attenuate the Lp(a) Cardiovascular Risk in Patients Who Underwent Percutaneous Coronary Intervention
Authors: Mahmoud Ahmed , Awad Kamal , FARINA JUAN , Abbas Mohammed Tiseer , Baba Nima , Abdalla Hesham , Badr Amro , Elahi Muhammed , Kamel Moaz , Pereyra Milagros , Scalia Isabel , Ayoub Chadi , Arsanjani Reza
Published: November 2024

Background:
Secondary prevention after percutaneous coronary interventions (PCIs) is still challenging and lipoprotein(a) [Lp(a)] is believed to be a residual risk factor in this setting. However, the effect of Lp(a) in case of well-controlled low-density lipoprotein cholesterol (LDL-C) is still unclear. The interaction between Lp(a) and LDL-C has been studied in primary prevention but still needs to be investigated in secondary prevention.

Hypothesis:
Achieving adequate LDL-C control after PCI may reduce the cardiovascular (CV) risk associated with Lp(a).

Methods:
A retrospective study of consecutive patients who underwent PCI and reached their LDL-C target levels (<70mg/dL) at three academic centers sites between 2006 and 2017. All included patients must have an Lp(a) measurement before the PCI intervention. Clinical outcomes on 10-year follow-up were collected by reviewing the electronic patients' records. The primary outcomes included all-cause mortality (ACM) and major adverse CV events (MACE) including non-fatal MI, ischemic stroke, coronary revascularization, and CV death. Kaplan-Meier curves were created to compare the survival probabilities among patients with high Lp(a) (≥50mg/dL) versus those with low Lp(a) (<50mg/dL). Univariate and multivariate Cox regression analyses were performed to quantify the association of elevated Lp(a) with outcomes and control for potential confounders.

Results:
In total, 878 patients (median age = 68 years, 74% males) were included in the analysis. Of them, 242 (27.6%) had high Lp(a) ≥50mg/dL. Kaplan Meier analyses did not reveal any significant difference in survival probabilities across the Lp(a) groups for any of the outcomes (Figure 1). The results were consistent in univariate (MACE, HR: 1.08 [95%CIs 0.85-1.35]; ACM, HR: 0.97 [95% CI 0.76-1.23]) and multivariate analyses (MACE, HR: 1.14, [95% CIs 0.90-1.45]; ACM, HR: 1.08 [95% CI 0.84-1.39]).

Conclusion:
These findings suggest that, in patients who underwent PCI and achieved an LDL-C target of <70 mg/dL, elevated Lp(a) levels were not associated with and increased risk of MACE or mortality. Controlling the LDL-C should still be the cornerstone in secondary prevention after PCI, however, larger prospective studies are still warranted to validate our results.
Abstract 4143003: Association of Mitral Regurgitation with Heart Failure Subtypes in Patients with Chronic Kidney Disease: the CRIC Study
Authors: JIN XUANYI , Chen Jing , He Hua , Zhao Cong , Richardson Sydney , Wright Layla , Suayp Oygen , Alvarado Flor , Alper Arnold , Bazzano Lydia , Mills Katherine , He Jiang
Published: November 2024

Background:
Data on the association between mitral regurgitation (MR) and heart failure (HF) subtypes in participants with chronic kidney disease (CKD) are scarce.

Hypothesis:
We hypothesized that the worsening of MR severity is associated with the incidence of both HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction in participants with CKD. Additionally, these associations may differ by sex, race, or the presence of atrial fibrillation (AF).

Methods:
We studied participants with CKD who had an echocardiography exam (2013-2015) in the Chronic Renal Insufficiency Cohort (CRIC) study and were free of HF at the time of enrollment in the study. The incidence of HFpEF and HFrEF was determined and classified based on the hospitalization diagnosis and ejection fraction measured by echocardiography during the hospitalization or follow-up visits. The level of MR severity was categorized as absent/trace, mild, and moderate/severe based on visualization and quantification of the effective regurgitant orifice area from an apical-four chamber. Multivariable Cox hazard models were used to examine the association of MR degree with the incidence of overall HF, HFpEF, and HFrEF.

Results:
Among 2951 participants with CKD (58.9 years, 46.1% women, and 73.4% with MR), 309 incident HFpEF and 322 incident HFrEF were confirmed during follow-up. Worsening MR severity was associated with the incidence of HFpEF (hazard ratio [HR] 1.65,
p
=0.04) and HFrEF (hazard ratio 1.91,
p
<0.001), independent of traditional clinical risk factors, ejection fraction, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio (
Table 1
). In addition, AF accounted for 10.1% and 11.1% of the association of MR severity with HFpEF and HFrEF, respectively. Furthermore, MR severity was associated with HFrEF in women (HR 4.04,
p
<0.001,

p
sex-

interaction
=0.0019), but not in men (HR 1.20,
p
=0.80).

Conclusion:
In patients with CKD, worsening MR severity was significantly and independently associated with the risk of HFpEF and HFrEF. These associations are partially explained by the presence of AF.
Abstract 4143006: Systemic Vascular Damage and Cardiac Dysfunction in a Mouse Severe Acute Pancreatitis Model
Authors: Du Aolin , Zhang Junmeng , Huo Yu , zhao debiao , Fayyaz Ahmed , Buglioni Alessia , Sangaralingham Jeson , Lugea Aurelia , Waldron Richard , Pandol Stephen , Redfield Margaret , Ji Baoan , Wang Ying
Published: November 2024

Background and Objective:
Decline of cardiovascular (CV) function is commonly observed in patients with severe acute pancreatitis (AP), which is associated with high mortality and morbidity. While the pathological changes in the pancreas during severe AP have been extensively studied, the impact on the CV system has not been well characterized. Furthermore, obesity is a major risk factor for severe AP. Hereby we utilized an obesity-associated mouse AP model to assess potential alterations in vascular integrity and cardiac function, two major components of circulatory failure.

Methods:
Wild-type male C57BL6J mice were fed a normal or a high fat (to induce obesity) diet. Both groups received intraperitoneal injection of cerulein (100 mg/kg/h x12) to induce AP. H&E and TUNEL staining of pancreas were performed to assess histology and cell death. To measure vascular integrity, we measured the leakiness of a fluorescein-conjugated dextran (70 kDa) in tissue parenchyma and serum levels of soluble vascular endothelial (VE)-cadherin, which has recently shown to be shed from endothelial cells with disrupted adherens junctions. Cardiac systolic and diastolic function were assessed by echocardiography at baseline and post-AP induction.

Results:
Compared to lean mice, obese mice developed more severe pancreatic edema, cell death and inflammatory cell infiltration, along with significantly increased accumulation of fluorescent dextran in multiple organs including pancreas, heart, lung, and kidney, suggesting systemic disruption of vascular integrity. Increased serum levels of soluble VE-cadherin in obese mice (vs. lean) after AP induction further supported compromised endothelial cell barrier function. At baseline, obese mice exhibited similar cardiac function to lean mice. However, obese mice, but not lean mice, developed impaired systolic and diastolic function post-AP induction, as supported by decreased ejection fraction and e’ velocity respectively.

Conclusion:
In this obesity-associated severe AP mouse model, systemic vascular permeability is increased, and cardiac function is substantially compromised. Systemic vascular hyperpermeability and cardiac dysfunction may represent therapeutic targets to enhance the outcomes in severe AP.
Abstract 4143017: Insights for Direct-to-Patient Clinical Trial Recruitment Strategies From the Heartline Study
Authors: Hills Mellanie , Korjian Serge , Chi Gerald , Natale Andrea , Saxon Leslie , Ferdinand Keith , Kwaku Kevin , Brancato Scott , Baca-Motes Katie , Steinhubl Steve , Wessler Jeff , Goldberg Nieca , Asthana Anisha , Shute Kate , Applebaum Jill , Doran Kathleen , Nikolovski Janeta , Kaul Simrati , Wentworth Dereck , Damaraju CV , DeFalco Frank , Tavakoli Cammie , Patel Mithun , Curtis Anne , Spertus John , Gibson Charles
Published: November 2024

Background:
Decentralized clinical trials using direct-to-participant recruitment can potentially engage large, representative participant pools.

Research Question:
Can a decentralized clinical trial use a multichannel approach to recruit patients >65 years old across the United States?

Goals/Aims:
To share insights on multichannel strategies for participant recruitment in the decentralized, app-based Heartline study.

Methods:
Heartline is a randomized trial testing the impact of a mobile app-based heart health program with the electrocardiogram (ECG) and Irregular Rhythm Notification (IRN) features on Apple Watch for early diagnosis, treatment, and outcomes of atrial fibrillation. Eligible participants were US adults aged ≥65 years with an iPhone and Medicare coverage. Multiple pathways for broad outreach were explored, including digital (eg, email, social media) and traditional channels (eg, direct mail, community outreach). Recruitment efforts were assessed and refined to reach a large eligible population.

Results:
A multichannel approach led to ~300,000 Heartline study app installations. In total, 34,244 participants completed enrollment (Feb 2020-Dec 2022), of whom 28,155 completed baseline demographic assessments. Participants were widely distributed geographically, with notable representation of outlying and rural areas (
Figure 1
). Women accounted for 54% of the participants. Overall, most participants were White (93.0%), with Asian, Black, and Hispanic participants representing 2.8%, 2.7%, and 2.5%, respectively.

Conclusion:
The Heartline study demonstrated the ability to recruit large numbers of participants aged ≥65 years using a direct-to-participant approach. Broad outreach strategies ensured gender and geographic diversity, enrolling a higher percentage of women than typical cardiology trials, and participation from rural areas. However, underrepresentation across racial/ethnic groups persisted and strategies to increase enrollment are needed. For similar trials, a strategic multichannel approach, with strong data and analytics capabilities may be beneficial to effectively target and enroll eligible participants.
Abstract 4143034: High-Intensity Statins in Veterans with Peripheral Artery Disease
Authors: Girotra Saket , Li Qiang , Vaughan Sarrazin Mary , Nathani Rohit , Chan Paul , Nguyen Cathy , Hoffman Richard , Minniefield-Young Nicole , Tsai Shirling , Gobbel Glenn , AL-GARADI MOHAMMED , Smolderen Kim , Arya Shipra , Beckman Joshua , Lund Brian
Published: November 2024

Background:
Current guidelines recommend high-intensity statins in patients with peripheral artery disease (PAD) to reduce the risk of cardiovascular and limb events. The extent to which these recommendations have been adopted in a large integrated health system remains uncertain.

Methods:
Using a novel natural language processing system that we previously developed and validated for identifying PAD, we created a registry of patients with a new diagnosis of PAD during 2015-2020 in the Veterans Health Administration (VHA). We used VHA pharmacy data to determine rates of active statin use at index date (date of PAD diagnosis), new initiation, persistence, and adherence (definitions in Table 1). High-intensity statin was based on statin type and dose. Analyses were also stratified by presence of pre-existing atherosclerotic cardiovascular disease (ASCVD), which was defined as a prior history of coronary or cerebrovascular disease.

Results:
Among 103,748 patients, 64,159 (61.8%) were on statins at index date (baseline) and 30,968 (29.8%) were on high-intensity statins (Table 1). An additional 14,219 patients (13.7%) initiated statins within 1 year of PAD diagnosis, of whom 6,384 (6.2%) initiated high-intensity statins. Rates of active baseline use, or new initiation in 1 year were much lower in patients who did not have pre-existing ASCVD, compared to those with ASCVD (Table 1). Persistence with therapy among total active users was 78.0% for any statin and 78.6% for high-intensity statins. Mean adherence among persistent users was >80% for any statin and high intensity statin. Persistence and adherence did not differ in subgroups stratified by ASCVD.

Conclusion:
Although more than 75% PAD patients were already on, or initiated a statin within 1 year of PAD diagnosis, only 36% were on high-intensity statins. Baseline use and new initiation of any statin and high-intensity statin was lower in PAD patients who did not have co-existing ASCVD. Overall, persistence among active users, and adherence among persistent users was high, and did not differ by statin intensity or pre-existing ASCVD. Given the strong evidence supporting high-intensity statins in PAD, interventions targeting intensifying statin therapy in PAD, especially in those without pre-existing ASCVD are warranted.
Abstract 4143048: Role of Inflammatory Cytokines in Triggering Ventricular Arrhythmias in Pulmonary Hypertension
Authors: Bronk Peter , Zhang Peng , Wang Eric , Radice Glenn , Tran Cao , Choudhary Gaurav , Choi Bum-rak
Published: November 2024

Introduction:
Pulmonary hypertension (PH) is a deadly disease, and the corresponding survival rates are estimated at 50% over 5 years. Most patients with severe PH die of right heart failure or sudden cardiac death from arrhythmias. There are strong indications supporting inflammation as a major proarrhythmic factor in PH.

Goal:
To investigate whether and how inflammatory cytokines promote cardiac arrhythmias in PH rat model.

Methods:
We used rat models of PH: 1) decompensated PH using Su5416 injection (SU) and 3 weeks of hypoxia (Hx) (Su/Hx, n=7), 2) compensated PH using Hx alone (n=3), 3) sham control (CTR, n=8). Interleukin 1b (IL-1b) and IL-18 were perfused (5 ng/ml for 90 min) and action potentials (AP) were mapped using optical mapping with voltage sensitive dye.

Results:
APDs in the right ventricle (RV) were significantly increased in Su/Hx (86±9 ms, p=0.014) vs. Hx (75±10 ms) and CTR (74±8 ms). APD dispersion is also increased in Su/Hx (23±3 ms, p=0.011) vs. Hx (8±3 ms) and CTR (9±4 ms), leading to conduction block and reentry formation around RVOT in Su/Hx during S1S2 programmed stimulation (Fig-A). Longitudinal conduction velocity (CV) is significantly slower in Su/Hx (0.58±0.08 m/s, p=0.01) vs. Hx (0.78±0.12 m/s) and CTR (0.84±0.10 m/s). Perfusion of IL-1b/IL-18 significantly prolongs APDs in the Su/Hx model (Fig-B, APD=109±19 ms, p=0.003) but not in Hx (78±13 ms) and CTR (83±7 ms), associated with frequent PVCs in Su/Hx model (Fig-C.D, n=5/7 hearts in Su/Hx vs. 0/3 in Hx only and 2/8 hearts in CTR), indicating that inflammatory cytokines increase arrhythmia risks in decompensated PH.

Conclusion:
More severe form of PH (Su/Hx) showed the highest arrhythmia risks compared to the compensated PH model (Hx) and control under IL-1b/IL-18 perfusion, supporting the idea that inflammation in PH may play key roles promoting electrical remodeling and arrhythmias.
Abstract 4143070: Institutional Demographics and Outcomes of Admitted Patients with Hypertensive Disorders of Pregnancy
Authors: Azzi Marly , Potchileev Sanela , Burns Luke , Mueller Ariel , Rana Sarosh
Published: November 2024

Background:
Hypertensive disorders of pregnancy (HDP) serve as the second leading cause of maternal mortality globally and represent a threat to pregnancies across our nation. Blood pressure goals and practice patterns continue to vary broadly between and within institutions. An updated analysis of the management and outcomes of HDP is necessary. The aim is to evaluate maternal and neonatal outcomes for patients admitted due to HDP at our institution.

Methods:
Patients (≥18 years of age) 23
+0
to 34
+6
weeks’ gestation who were hospitalized at the University of Chicago with a HDP associated condition between January 1
st
, 2022, and January 31
st
, 2024 were included in this cohort study. Demographics, maternal/neonatal events, and the correlation between interventions received during pregnancy and HDP outcomes were assessed.

Results:
Our study included 140 patients with HDP, of which 46 (32.9%) had preeclampsia (preE) with severe features (SF), 13 (9.3%) had preE without SF, 10 (7.1%) had gestational HTN, and 26 (18.6%) had cHTN. Our cohort was predominantly African American (n = 86; 61.4%) with median age 31 years (IQR 26, 35). Among patients with a preterm delivery (80.4%), the most common indication for delivery was persistent severe hypertension (81.1%). Modest correlations were observed between birthweight percentile and both systolic BP (Spearman r = -0.189 [95% CI: -0.368, 0.004]; p = 0.06) and diastolic BP (r = -0.197, [95% CI: -0.373, -0.002]; p = 0.047), with BP decreasing as the percentile increased. Figure 1 outlines the latency between admission date and delivery. Patients on an antihypertensive medication at the time of postpartum discharge were less likely to be readmitted within six weeks (9.0% vs 22.0%; p = 0.03) due to BP control as compared to patients who were not on medication.

Conclusion:
This study demonstrates that severe HTN feature of HDP is most associated with neonatal adverse outcomes and maternal postpartum readmissions. Patients with HDP can benefit from an improved stratification tool during antepartum and at discharge to identify patients at higher risk of neonatal/maternal adverse outcomes.
Abstract 4143073: Comparative Clinical Outcomes Following Transcatheter Mitral Valve repair in Patients with a History of Adverse Pregnancy Outcomes Versus Those Without: A National Inpatient Sample Analysis
Authors: Awoyemi Toluwalase , Odo Chinenye , Ogunniyi Kayode , Bolakale-Rufai Ikeoluwapo , Tolu-Akinnawo Oluwaremilekun , Gwira-Tamattey Edwin , Teeri Samira , Alagbo Habib , Daniel Emmanuel , Ebubechukwu Ugochukwu , Odoh Ikenna , Mutebi Cedrick
Published: November 2024

Background:
Adverse pregnancy outcomes (APO) pose long-term cardiovascular risks. Considering the potential impact of APO on maternal health, this study aims to investigate the characteristics and clinical outcomes of women who have experienced APO and subsequently undergo transcatheter mitral valve repair (TMVr).

Methods:
This is a retrospective cohort study that analyzed data from 15,220 women who underwent transcatheter mitral valve repair (TMVr) and it was divided into two groups: history of adverse pregnancy outcome (APO, n=3240) and without a history of APO (No APO, n=11,980). Comparative analyses between the APO and No APO groups were performed using t-tests for continuous variables and chi-square tests for categorical variables. Multivariate logistic regression models were employed to adjust for potential confounders and identify independent predictors of in-hospital mortality and other adverse outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each variable.

Results:
Patients with a history of adverse pregnancy outcomes (APOs) were younger (mean age 73.3 vs. 79.0 years, p<0.001) and more frequently identified as Black/African American (20.9% vs. 8.0%, p<0.001). They had a higher mean Charlson Comorbidity Index (3.2 vs. 2.8, p<0.001). After adjustment, these patients were more likely to require mechanical ventilation (OR 0.76, 95% CI 0.61-0.94, p=0.0112) and vasopressors (OR 1.37, 95% CI 1.05-1.79, p=0.0205), experience heart block (OR 2.29, 95% CI 2.00-2.63, p<0.001), and develop acute kidney injury (OR 1.26, 95% CI 1.12-1.42, p=0.0001). However, the adjusted odds of in-hospital mortality did not differ significantly between the groups (OR 0.99, 95% CI 0.73-1.32, p=0.9355).

Conclusions:
Women with a history of adverse pregnancy outcomes (APOs) undergoing TMVr face higher risks of complications, such as heart block and acute kidney injury, highlighting the importance of incorporating pregnancy history into cardiovascular risk assessment and management for these patients.
Abstract 4143088: Abnormal Calcium Regulation Leads to Pathological Cardiac Hypertrophy During Pregnancy in the GSNOR-Deficient Mouse Model of Preeclampsia
Authors: Dulce Raul , Balkan Wayne , Hare Joshua , Kulandavelu Shathiyah
Published: November 2024

Introduction:
Preeclampsia (PE), a leading cause of maternal mortality, is linked to cardiac hypertrophy and impaired relaxation, predisposing the mother to an increased risk of cardiovascular (CV) injury during pregnancy. Mice lacking S-nitrosoglutathione reductase (GSNOR

–/–
mice

) exhibit all the clinical features of PE. Calcium regulation plays an important role in cardiac relaxation and hypertrophy, but whether alterations in calcium handling contribute to the impairment in these PE mice is unknown.

Hypothesis:
Cardiac hypertrophy and impaired relaxation in pregnant GSNOR

–/–

mice may be due in part to altered Ca
2+
handling mechanisms.

Methods:
Pregnant control (WT [C57B6]) and GSNOR

–/–

mice were examined at non-pregnant (NP) and late pregnancy (17.5 dpc). Cardiomyocytes (CMs) were isolated (N=3-4 mice/group; n=8-24 CMs/heart) and assessed for intracellular Ca
2+
and sarcomere shortening using IonOptix. Ca
2+
decay and sarcomere relaxation rates were recorded. Ventricular tissue homogenates were assessed for Ca
2+
handling and sarcomere-associated protein expression and post-translational modifications by Western Blot.

Results:
At late pregnancy, the
CMs of
GSNOR

–/–

mothers
were significantly wider
and systolic and diastolic Ca
2+
levels were elevated as compared to WT. At 17.5 dpc, expression of Ca
2+
handling proteins, RyR2, L-TCC and NCX1 were increased, and phosphorylation of RyR2 and L-TCC were increased in the GSNOR

–/–

mothers as compared to WT. The Ca
2+
decay rate improved in CMs from pregnant versus NP WT CMs but not in GSNOR

–/–
CMs.

PLB phosphorylation at Thr-17 was augmented in pregnant WT hearts, while phosphorylation at Ser-16 was reduced in pregnant GSNOR

–/–
.

Sarcomere relaxation parameters and sarcomere resting length were improved in CMs from pregnant WT mice but were impaired in pregnant versus NP GSNOR

–/–
mice in association with increased expression of MyBPC in pregnant GSNOR
–/–
.

Conclusion:
The PE-related cardiac hypertrophy and impaired relaxation at late pregnancy in GSNOR

–/–

mice were associated with elevated cytosolic Ca
2+
levels, altered expression and post-translational modifications of Ca
2+
handling and sarcomeric proteins, which may predispose these mice to higher CV injury during pregnancy
Abstract 4143092: Impact of Lifelong Exercise on Left Ventricular Wall Stress
Authors: Will Lexis , Levine Benjamin , Sarma Satyam
Published: November 2024

Background:
Very high level, lifelong aerobic exercise results in lower ventricular stiffness and left ventricular wall stress (LVWS) LVWS is an important predictor of future heart failure risk. To what degree LVWS changes with various doses of lifelong aerobic exercise is unknown.

Objective:
The purpose of this study was to determine the impact of lifelong exercise on LVWS.

Methods:
Seniors (n = 58) who consistently participated in lifelong patterns of exercise training were recruited and categorized into 3 groups: “sedentary” (<1 exercise sessions/week); “moderate” (2 to 3 sessions/week); and “active” (4 to 7 sessions/week). Right heart catheterization and echocardiography were performed at baseline (x 2; once before lower body negative pressure (LBNP) and again before saline infusion) and while manipulating preload using LBNP (-15 mmHg suction) and rapid normal saline (NS) infusion (15 mL NS/kg). LVWS was calculated from pulmonary capillary wedge pressure (PCWP) and LV wall thickness and radius using Law of Laplace and expressed in Pascals (Pa). Strain was calculated using (V−Vmin)/Vmin, where Vmin was the smallest end-diastolic volume measured (during LBNP) and V was the volume during each condition.

Results:
LVWS increased as preload increased. As shown in the figure, peak LVWS during saline load (top panel: sedentary 3.1 +/- 1.1 Pa, moderate 2.5 +/- 0.7 Pa, active 2.3 +/- 0.5 Pa) and stress-strain slopes (sedentary 12.3 +/- 10.3, moderate 6.5 +/-4.1, active 5.7 +/- 2.7 Pa) were highest in sedentary seniors compared to seniors in the moderate (p=0.008) and active groups (p=0.006).

Conclusions:
In healthy, older individuals, lower LVWS was apparent even with lifelong, moderate levels of physical activity (2 to 3 sessions/week) and similar to those who exercised at more frequent levels (4-7 times per week). Exercising 2 to 3 times a week may provide a sufficient “dose” to reduce LVWS, highlighting the benefits of even casual training on ventricular structure and potential to mitigate the lifetime risk of heart failure with exercise.
Abstract 4143094: COVID-19 Infection Had Significant Impact on In-Hospital Outcomes of Women with Peripartum Cardiomyopathy
Authors: Pattoli Megan , Desai Spandan , Roma Nicholas , Miller Luke , Magid Lindsey , Amaratunga Eluwana , Shirani Jamshid
Published: November 2024

Background:
Peripartum cardiomyopathy (PPCM) is defined as a dilated form of cardiomyopathy that occurs within the last month of pregnancy and up to 5 months postpartum. The etiology is likely multifactorial and viral infections may account for up to a third of PPCM cases. We aimed to examine the impact of concurrent COVID-19 infection on in-hospital outcomes of women with PPCM.

Methods:
National Inpatient Sample was queried to identify women admitted with PPCM with COVID-19 (group A) between the years 2020-2021 and without (group B) concurrent COVID-19 infection between the years 2016-2019.

Results:
A total of 19135 women were admitted with PPCM between the years 2016-2021, of whom 420 (2%) had concurrent COVID-19 infection. Group A PPCM followed a seasonal pattern with peak incidence in fall (43%) followed by winter (31%), spring (13%) and summer (13%) [p=0.002]. Group A was more often Hispanic (20.3% -vs- 10.8%, p<0.001) and more often admitted to urban teaching hospitals (88.1% -vs- 79.7%, p<0.001), had longer length of stay (9.7 -vs- 5.8 days), and overall greater cost of hospitalization ($162181 -vs- $92155). Group A also had greater rates of acute myocardial infarction (11.9% -vs- 5.6%, p<0.001), bleeding requiring transfusion (8.3% -vs- 5.4%, p=0.030), pulmonary embolism (4.8% -vs- 2.4%, p=0.057), shock (14.3% -vs- 3.1%, p<0.001), ICU admission (29.8% -vs- 10.2%, p<0.001), vasopressor requirement (10.7% -vs- 2.1%, p<0.001), ventilator requirement (27.4% -vs- 9.1%, p<0.001), and cardiopulmonary resuscitation (7.1% -vs- 1.1%, p=0.005). Overall in-hospital mortality was also higher in group A (8.3% -vs- 1.5%, p<0.001).

Conclusion:
PPCM appeared to follow a seasonal trend in incidence similar to COVID-19. COVID-19 infection may have accounted for some cases of PPCM and was associated with adverse in-hospital outcomes and higher mortality.
Abstract 4143095: Rural-Urban Disparities in Heart Transplant Outcomes for Heart Failure Patients: An Analysis of the National Inpatient Sample Dataset
Authors: Odo Chinenye , Awoyemi Toluwalase , Odoh Ikenna , Tolu-Akinnawo Oluwaremilekun , Ogunniyi Kayode , Barriga Guzman Rocio , Ezekwueme Francis , Alagbo Habib , Anuforo Anderson , Ebubechukwu Ugochukwu
Published: November 2024

Background: Disparities in healthcare outcomes between rural and urban populations are well-documented, yet limited research specifically addresses differences in heart transplant outcomes for heart failure patients.

Methods: We conducted a retrospective cohort study using the NIS dataset (2017-2020), analyzing 11,025 heart failure patients who received heart transplants. The cohort included 565 rural and 10,460 urban patients. We examined variables such as age, gender, hospital bed size, race, insurance status, and comorbidities. Primary outcomes included in-hospital mortality, mechanical ventilation requirement, length of stay, hospital charges, and vasopressor requirement. Multivariate logistic regression was performed to identify independent predictors of in-hospital mortality.

Results: Age was found to be a significant predictor, with each additional year increasing the risk of mortality (OR 1.026, 95% CI 1.017-1.034, p < 0.0001). Hospital bed size also played a critical role; patients in small hospitals had a significantly higher risk of mortality compared to those in large hospitals (OR 3.309, 95% CI 2.101-5.212, p < 0.0001), whereas patients in medium-sized hospitals had a lower risk (OR 0.374, 95% CI 0.236-0.592, p < 0.0001). While rural residency was associated with a higher mortality risk compared to urban residency, this association was not statistically significant (OR 1.40, 95% CI 0.95-2.07, p = 0.0860). Other factors, including the adjusted odds of vasopressor requirement (OR 1.13, 95% CI 0.92-1.39, p = 0.2524), need for mechanical ventilation (OR 1.12, 95% CI 0.87-1.43, p = 0.3741), length of stay (difference -0.005, 95% CI -8.57-1.33, p = 0.1709), and pacemaker insertion (OR 0.81, 95% CI 0.65-1.01, p = 0.062), did not show significant differences between groups.

Conclusion:

This study reveals that clinical outcomes post-heart transplant are comparable between patients in rural and urban settings. However, age and hospital bed size significantly influence mortality risk, with older age and treatment in smaller hospitals associated with higher mortality rates.
Abstract 4143109: Association Between Frailty Testing through Timed Up-and-Go Test Time and Mortality in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy
Authors: Paul Aritra , Demian Joe , Varma Niraj , Finet J. Emanuel , Kochar Arshneel , Bader Feras , Wazni Oussama , Tang Wilson , Rickard John
Published: November 2024

Background:
The use of cardiac resynchronization therapy (CRT) devices has significantly increased in usage in recent years. Identifying predictors of mortality in CRT patients remains an area of investigation.

Objective:
To establish a relationship between timed up-and-go test time (TUGT) and mortality in heart failure patients (HF) with CRT devices.

Methods:
This retrospective study included 506 patients with heart failure with reduced ejection fraction (HFrEF) who underwent CRT implantation at our institution between 2017-2022. All patients were followed up with a multidisciplinary team, including electrophysiology and HF physicians about 6 months after CRT implantation, where frailty was assessed. We used TUGT as a measure of frailty and divided patients into 2 groups: TUGT: >15 seconds (n=73) and ≤15 seconds (n=433). The primary endpoint was a composite of left ventricular assist device implantation, transplant, or death at 2 years post-CRT. Data was collected retrospectively from electronic medical records.

Results:
The study population was 65.6% male, with a mean age of 69.1 years, and 79.4% of devices being CRT-D.Response was defined as an improvement in LVEF >5% with reduction in LVESV>10%; anybody not meeting this definition was classified as a non-responder. Responder and non-responder rates among TUGT >15 and TUGT
<
15 were 60.3% vs 69.3%; and 39.7% vs 30.7%, respectively. The median (IQR) timed up and go time was 9.25s (7.48-11.7s). 52 (10.3%) patients had a composite outcome within 2 years follow up. Univariate analysis revealed that higher TUGT was significantly associated with worse outcomes (median TUGT 9.07 vs 11.9s; p<0.001). Multivariate cox regression also revealed TUGT>15s to be an independent predictor of our composite outcome [HR= 3.47 (1.71-7.06); p=0.001] (Table 1), with adjusted survival curves showing patients with TUGT>15s have worse outcomes (Figure 1).

Conclusion:
Frailty testing using TUGT post-CRT implantation is a strong predictor of mortality in HFrEF patients after CRT implantation.
Abstract 4143130: Regression of Inflammation in Chronic Chagas Disease Using Specific Anti-Parasitic Therapy Is Associated With an Activated Immune Profile Before Therapy and Increased Levels of IL-17 After Therapy
Authors: Silva Silvana , Dutra Walderez , Barros Marcio , Nunes Maria , Ribeiro Antonio , Sabino Ester Cerdeira , Oliveira-da Silva Léa , Koh Carolina , Carvalho Andrea , Araujo Fernanda , Pacheco Iago , Muniz Meira Geanne , Silva Ambrósio Vieira Gustavo Henrique , Ferreira Iago , Machado Jean , Nyssen Jeroen , Zanetti Sofia , dos Santos Tiago
Published: November 2024

Background:
Chagas disease (CD), caused by Trypanosoma cruzi, leads to chronic Chagas cardiomyopathy, one of the deadliest and most debilitating cardiopathies. Benznidazole (BZN) is the medication of choice in Brazil, effective during the acute phase, but its efficacy during the chronic phase is unclear.

Aims:
To determine if BZN treatment reduces cardiac inflammation and fibrosis via magnetic resonance imaging (MRI) and its association with the circulating immune profile of CD patients.
Methods:
We collected cardiac images and plasma from a cohort of CD patients before and 6 months after BZN treatment. We performed: 1- MRI of left and right ventricle function and volumes, T1 (MAPA T1), T2 mapping (MAPA T2), and extracellular volume (ECV); 2- analysis of soluble factors including cytokines, chemokines, and growth factors using the Bio-48 Plex Human Cytokine Screening Panel kit. Changes in the variables MAPAT1, MAPAT2, and ECV were used to classify the improvement of CD patients undergoing BZN therapy. Patients with the greatest reductions in these variables post-therapy, compared to pre-therapy, were considered to have greater clinical improvement. Thus, patients were divided into two groups: greater clinical improvement (GCI; n=15) and smaller clinical improvement (SCI; n=15) (figure 1). Data were analyzed using GraphPad Prism 8 software with statistical significance set at p<0.05.

Results:
Analysis of MAPA T1, MAPA T2, and ECV showed a reduction of fibrosis/inflammation in patients after treatment as compared to before. Our data demonstrated that GCI patients had an activated systemic immune profile before treatment, with higher levels of NGF (p=0.04), CXCL-8 (p=0.03), CCL-7 (p=0.04), IL-12 (p=0.04), IL-13 (p=0.03), and IL-15 (p=0.03) compared to SCI patients (figure 2A). Interestingly, GCI patients displayed higher post-treatment levels of IL-16 (p=0.02) and IL-17 (p=0.048) (figure 2B).

Conclusion:
These results suggest that BZN treatment may reduce fibrosis/inflammation in cardiac tissue of CD patients and that an activated immune profile before therapy may predict therapeutic response. Additionally, increased levels of IL-17 post-therapy in GCI patients support IL-17's previously reported protective role in Chagas disease.
Abstract 4143148: Feasibility of Volumetric Echo-PIV for Assessing Right Ventricular Blood Flow in Pulmonary Hypertension
Authors: Hashemi Mohammad , Salinas Nancy , Brown Tawnya , Caudill Antonina , Jackman Susan , Matusov Yuri , Singh Siddharth , Pedrizzetti Gianni , Kheradvar Arash
Published: November 2024

Background:
Pulmonary hypertension (PH) is a progressive condition leading to right ventricular (RV) dilatation and failure. It is hypothesized that RV remodeling can be predicted by changes in the complex three-dimensional (3D) RV blood flow. Early identification of these changes could help prevent establishing overt PH. This study tests the feasibility of volumetric Echo-PIV (V-Echo-PIV) technique that considers conservation of mass principle and RV wall dynamics to assess 3D RV blood flow field using standard clinical echocardiography equipment.

Hypothesis:
To assess whether V-Echo-PIV can differentiate between normal and pulmonary hypertension states without requiring high-fidelity replication of actual blood flows.

Goals:
Distinguishing RV blood flow in PH with or without RV dysfunction compared to the normal state.

Methods:
Followed by Optison™ injection, contrast echocardiography using a Philips EPIQ CV9 system and 3D matrix probe (x5-1) was performed to capture B-mode images of the RV. The V-Echo-PIV method estimated 3D RV blood flow velocities, refined by iterative correction to comply with RV geometry and mass conservation. Global flow properties such as kinetic energy and vortex impulse were calculated to distinguish between normal and pathological conditions.

Results:
The study compared healthy RV with the RVs from patients with pulmonary hypertension, with a normal-sized RV and with a dilated and dysfunctional RV. Evaluation of the iterative flow estimation process showed rapid convergence, confirming the robustness of the refinement approach. Blood flow visualization revealed distinct patterns during diastolic filling and systolic ejection (Fig. 1). Quantitative analysis showed reduced intensity of cycle-averaged kinetic energy, the energy dissipation, and enstrophy along with diastolic average of vortex impulse in patients compared to the control subject, indicating altered blood flow dynamics in PH (Figs. 2 and 3).

Conclusions:
Results show PH patients have altered flow properties even without overt RV dysfunction based on the qualitative visualization and the global metrics of blood flow. Further studies are needed to validate clinical value and ensure statistical significance. Nevertheless, this study demonstrates the potential of V-Echo-PIV, enhanced by the principles of mass conservation and RV geometry dynamics, to distinguish between normal and diseased conditions without necessitating high-fidelity replication of actual blood flows.
Abstract 4143150: Long-term Effect of Screening for Coronary Artery Disease Using CT Angiography on Mortality and Cardiac Events in High-risk Patients with Diabetes: the FACTOR-64 Follow-up Study
Authors: Muhlestein Joseph , May Heidi , Knight Stacey , Le Viet , Bair Tami , Anderson Jeffrey , Knowlton Kirk
Published: November 2024

Background:
The FACTOR-64 study was a randomized controlled trial designed to assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in high-risk patients with diabetes followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes. Results at four years showed a lower revascularization rate (3.1% (14) vs. 8.9% (40), p<0.005) among the control group. But there was also a non-significant trend toward a lower incidence of all-cause mortality and nonfatal MI (hazard ratio, 0.82 [95% CI, 0.49-1.32]; p=0.38). Whether screening CCTA might have a more significant effect on the outcomes of patients after longer follow-up is unknown.

Methods:
The FACTOR-64 study randomized 900 patients (age = 61.5 years, males = 52%, Type 2 DM = 88%, DM duration = 13 years) with type 1 or type 2 diabetes for at least 3 to 5 years without CAD symptoms to screening with CCTA (n = 452) or standard national guidelines-based optimal diabetes care (n = 448). Standard primary prevention medical therapy or aggressive secondary prevention therapy with invasive coronary angiography was recommended based on CCTA findings. Enrollment occurred between July 2007 and May 2013, and follow-up extended to May 2024.

Results:
The mean follow-up time was 12.7±3.2 (CCTA=12.8±3.1; control=12.6±3.3, p=0.47) years. During longer-term follow-up after the initial four years, essentially the same numbers of further revascularizations (20 vs. 21) occurred in the CCTA group vs. the control group, thus continuing a significantly higher rate of revascularization among those receiving CCTA (Table). However, the composite and individual outcomes of all-cause mortality and nonfatal MI did not differ between the CCTA and control groups.

Conclusion:
Among asymptomatic patients with type 1 or type 2 diabetes followed for over twelve years, the use of CCTA to screen for CAD did not significantly affect the rates of all-cause mortality or nonfatal MI. This was despite an overall significantly increased use of revascularization among those receiving CCTA. These definitive findings do not support CCTA screening in this population.
Abstract 4143155: Sex-Specific Coronary Plaque Characteristics and Risk of Cardiovascular Events: Insights from the ISCHEMIA Trial
Authors: Lakshmanan Suvasini , Wang Yixin , Chen Ying , Mancini G B John , Leipsic Jonathon , Budoff Matthew , Hague Cameron , Min James , Stone Gregg , Boden William , Spertus John , Bangalore Sripal , Hochman Judith , Reynolds Harmony , Maron David
Published: November 2024

Background:
Artificial-intelligence-enabled analysis of atherosclerotic plaque characteristics on coronary computed tomography angiography (CCTA) may improve sex-specific risk prediction of cardiovascular (CV) events.

Aims:
The aim of this study was to examine sex differences in CCTA-derived atherosclerotic plaque analysis in ISCHEMIA participants, and to identify any interaction between sex and the prognostic value of quantitative atherosclerosis parameters in predicting CV events.

Methods:
In a post-hoc analysis, atherosclerosis imaging quantitative CT (QCT) was performed on all available CCTA scans. Interaction analysis was performed to understand the impact of female sex on the relationship between QCT variables and the outcomes of CV death or myocardial infarction (MI), all-cause death, and MI alone over a median follow-up of 3.3 years.

Results:
Of the 3645 participants with CCTA available for analysis, mean age was 64 and 21% were female. Females had lower total, calcified, non-calcified, and low-density non-calcified plaque volume than males (p<0.001 for all, Table). Percent atheroma volume (PAV=total plaque volume /vessel volume x 100%) was associated with CV death or MI in all participants, and the association was stronger in females (univariate HR: 2.37, 95% confidence interval (CI) 1.79, 3.14, p<0.001) than men (HR: 1.70, 95% CI 1.45, 2.00, p<0.001). There was a significant interaction showing accentuated risk of CV death or MI associated with greater PAV among females vs. males (HR for female*PAV: 1.42, 95% CI 1.03, 1.95, p=0.032, Figure), mainly driven by risk for MI.

Conclusions:
In ISCHEMIA, females presenting with moderate or severe ischemia and obstructive CAD had less atherosclerotic plaque burden of all subtypes and less adverse plaque characteristics identified by CCTA than men. The risk associated with greater atherosclerotic burden (PAV) was higher among female participants than males for the composite outcome of CV death or MI.
Abstract 4143156: Can Ventricular-Paced 12-Lead ECG Markers Predict Sudden Cardiac Death?
Authors: Truyen Thien Tan Tri Tai , Uy-Evanado Audrey , Nakamura Kotoka , Chugh Harpriya , Reinier Kyndaron , Chugh Sumeet
Published: November 2024

Introduction:
Specific markers on the sinus rhythm ECG are independently associated with increased risk of sudden cardiac death (SCD) with several published ECG risk scores. However due to distinctive activation of the heart, ventricular-paced (VP) ECGs are typically excluded from these studies, especially in the general population.

Hypothesis:
Markers on the VP ECG can predict risk of SCD in the general population.

Methods:
We conducted a case-control analysis in an ongoing community-based study of SCD in the Northwestern US (catchment population ~ 1 million; 2002-2020). SCD cases were included if they were aged ≥18 years, had archived ECGs performed prior to and unrelated to SCD that demonstrated continuous ventricular pacing. Control participants with identical ECG selection criteria and no history of ventricular arrhythmias or cardiac arrest were recruited from the same geographical area. Individuals with biventricular pacing and fusion rhythm were excluded. The ECG markers analyzed included QRS duration, QT, QTc, JTc, Tpeak-end, and heart rate.

Results:
Among 104 cases and 36 controls meeting criteria, VP SCD cases exhibited significantly longer QRS duration (median 172 ms, interquartile range [IQR] 157-192 vs. 161 ms, IQR 144-172, p=0.02), QTc (median 521 ms, IQR 495-560 vs. 511 ms, IQR 483-529 ms, p=0.001), and Tpeak-end interval (median 113 ms, IQR 97-124 vs. 99 ms, IQR 84-111, p=0.02) than VP controls. The highest quartile of QRS duration, QTc, and Tpeak-end were associated with 3.9, 7.6, and 5.2-fold higher odds of SCA, respectively, compared to the lowest quartiles. After performing multivariable regression analysis with demographic factors and comorbidities, QRS duration and Tpeak-end remained independent predictors of SCA (Figure).

Conclusion:
Our findings suggest that specific markers from ventricular paced ECGs are also associated with SCD. Further investigation is warranted to validate these results in other populations and to explore the implications for SCD risk stratification in the previously neglected sub-group of individuals with ventricular-paced rhythms.
Abstract 4143173: B Cell CXC Chemokine Receptor Type 5 Expression Predicts Left Ventricular Functional Improvement and Neurohormonal Improvement After Cardiac Resynchronization Therapy
Authors: Bilchick Kenneth , Cochran Jesse , Kothari Hema , McSkimming Chantel , Bivona Derek , Zunder Eli , Bekiranov Stefan , McNamara Coleen
Published: November 2024

Introduction:
B cells infiltrate the heart in a CXC chemokine receptor type 5 (CXCR5)-dependent manner and influence inflammation and remodeling. Yet whether CXCR5 expression on circulating B cells can be used as a marker to identify patients more likely to respond to pacing therapies for heart failure (HF) like cardiac resynchronization therapy (CRT) is unknown

Research Question:
Is the amount of CXCR5 expression on circulating B cells in humans prior to CRT associated with measures of left ventricular (LV) functional and neurohormonal response to CRT?

Hypothesis:
We hypothesized that lower B cell expression of CXCR5 pre-CRT is associated with greater improvements in LV function and neurohormonal activation (B-type natriuretic peptide [BNP]) after CRT.

Methods:
Protein expression in cryopreserved peripheral blood mononuclear cells (PBMCs) was measured with cytometry by time of flight (CyTOF). CXCR5 expression in B cell subsets was evaluated before and six months after CRT in 24 patients. Cardiac magnetic resonance (CMR) was performed prior to CRT, and the LV end-systolic volume index (LVESVI) before and after CRT was assessed by echocardiography. Response was defined as a 15% reduction in the LVESVI six months after CRT.

Results:
In 24 patients with HF undergoing CRT, the median age was 68 years (IQR 61 to 75 years), 38% were female, and 15 were responders (R). The median pre-CRT serum BNP concentration was 178 pg/mL (IQR 94-251 pg/mL) in R and 430 (IQR 272-757 pg/mL) in non-responders (NR) (p=0.07). The median pre-CRT LVESVI was 74 mL/m
2
(IQR 60 to 103 mL/m
2
) in R and 90 mL/m
2
(IQR 83 to 110 mL/m
2
) in NR (p=0.19). Pre-CRT CXCR5 expression in naive B cells (CD27- IgDhiCD196lo IgMlo) was lower in R v. NR (p=0.0016) (Figure 1). The area under the receiver operating characteristic curve (AUROC) for response was 0.80 (p=0.0026) with B cell CXCR5 as the only predictor and 0.89 (p=0.0015) with both B cell CXCR5 and the pre-CRT CMR LV ejection fraction (LVEF) as predictors (Figure 2). The odds ratio for response per unit increase of B cell CXCR5 was 0.18 (p=0.027) in the latter model. Pre-CRT B cell CXCR5 expression was also correlated with the change in BNP six months after CRT (r=0.45, p=0.027) (Figure 3).

Conclusions:
B cell CXCR5 may be an important predictor of CRT response based on LV function and neurohormones even after adjustment for known predictors. Further investigation of B-cell CXCR5 for prognosis in HF patients undergoing CRT is of great interest.