bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4144077: Sudden death in hypertrophic cardiomyopathy – what is the role of coronary artery disease?
Authors: Chugh Harpriya , Uy-Evanado Audrey , Nakamura Kotoka , Reinier Kyndaron , Chugh Sumeet
Published: November 2024

Background:
Myocardial ischemia is a potential trigger for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) but significant coronary artery disease (CAD) is not considered in clinical risk stratification calculators. The overlap between HCM and CAD needs further investigation, especially in the general population.

Hypothesis:
A large proportion of patients with HCM who suffer SCD, have associated significant CAD.

Methods:
From an ongoing prospective, population-based study of SCD in the Northwestern US (catchment pop. ≈1 M, 2002-2020), we performed a case-case analysis. Comparisons of the lifetime clinical history and available autopsy findings were made between SCD cases with HCM and CAD(HCM-CAD) vs. HCM without CAD(HCM-NCAD). HCM was defined as left ventricle (LV) wall thickness ≥15mm in the absence of any other cause for LVH. Univariate and multivariate analyses were conducted.

Results:
A total of 5962 (male 67%, age 64±19yr, black 9%) SCD cases with detailed clinical data were evaluated and 2.9% (n=177, male 84%, age 46±16yr, black 12%) met criteria for HCM. HCM-CAD was observed in 86 (48.6%). When compared to HCM-NCAD (n=91), HCM-CAD were more likely to be male (93% vs 75.8%, p =0.002) and older (51±15 vs 41±16 years, p<0.0001) (Figure). The multivariable model showed that HCM-CAD were older (OR :1.1 [1.0-1.1]) and male (OR 5.9 [2.0-18.0]). Heart failure (OR 0.18 [0.05-0.68]) and asthma (OR 0.19 [0.05-0.71]) were more common in HCM-NCAD. Out of those with symptom data available (n=152), chest pain as a warning symptom was more common in HCM-CAD vs HCM-NCAD (20.8% vs 8%, p =0.03).

Conclusion:
Approximately 50% of HCM who suffered SCD had associated significant CAD, suggesting that myocardial ischemia could be an important trigger of SCD in HCM. These findings highlight the importance of CAD as a risk modifier for SCD in HCM and should be investigated further.
Abstract 4144097: Stealing from the Heart: A Case of Angina due to Coronary-Bronchial Artery Fistula after Pulmonary Embolism
Authors: Fordham Matthew , Ghazal Mohamad , Derakhshesh Matthew , Daghstani Omar , Nappi Anthony , Lyubarova Radmila , Belov Dmitri
Published: November 2024

Introduction:
Coronary-bronchial artery fistula (CBF) is a rare finding with an incidence of 0.08 to 0.61%. Patients may present with chest pain, dyspnea, or hemoptysis. Transcatheter interventions provide definitive treatment for symptomatic patients. Herein, we present a case of recurrent chest pain due to CBF involving the sinoatrial nodal (SAN) artery.

Case:
A 75-year-old lady presented with recurrent midsternal chest pain for several years. Her medical history was notable for pulmonary emboli (PE), and antiphospholipid syndrome. Initial investigation showed mildly elevated high sensitivity troponin to 28.9 ng/L. ECG showed normal sinus rhythm without ischemic abnormalities. Prior ischemic work-up including dobutamine stress echocardiogram and invasive coronary angiography was unremarkable. Ventilation perfusion (V/Q) scan showed multiple areas of VQ mismatch. Computed tomography coronary angiography (CTCA) showed a dominant RCA with a 2.5 mm communication between the SAN artery and left bronchial artery. After a heart team discussion, the patient was offered definitive treatment. A 6 Fr FR4 Mach 1 Guide catheter was used for selective right coronary angiography. A steerable microcatheter floppy 0.014”x 300 cm wire was used to engage the fistula originating from SAN artery (Figure 1). A micro vascular plug was successfully deployed over the wire without endangering sinus nodal supply. Post-intervention there was decrease in flow from the SAN to the bronchial artery (Figure 2). At one month follow up the patient was chest pain free.

Discussion:
Patients with pulmonary vascular disease might be predisposed to CBF, as chronic pulmonary ischemia might augment collateral blood flow. As a result, coronary steal phenomenon may lead to atypical angina. CTCA is a helpful screening tool, while transcatheter intervention may benefit symptomatic individuals.

Conclusion:
CBF should be considered in patients with history of PE and recurrent chest pain of unclear etiology.
Abstract 4144104: Intramyocardial Hydrogel Injections in Porcine Model of Infarction Remodeling Demonstrates Improved Left Ventricular Performance on Pressure-Volume Analysis Associated with Decreased Matrix Metalloproteinase Activation
Authors: Porcaro Olivia , Thorn Stephanie , Ahn Shawn , Lee Supum , Uman Selen , Lysyy Taras , Burns Rachel , guerrera nicole , Vermillion Billy , Spinale Francis , Duncan James S , Heerdt Paul , Burdick Jason , Sinusas Albert
Published: November 2024

Introduction:
Following myocardial infarction (MI), extracellular matrix (ECM) degradation significantly contributes to adverse left ventricular (LV) remodeling mediated by the activation of matrix metalloproteinases (MMPs). Intramyocardial injection of hydrogels that locally release MMP inhibitors are designed to modulate MMP activation, increase wall thickness, reducing wall stress, resulting in improved regional mechanics and function. Pressure-volume (PV) analysis is an established approach for evaluation of cardiac performance.

Methods:
Chronic reperfused MI was created by a 90-min LAD occlusion in swine (n=16). PV loop analysis was performed using simultaneous 3D echocardiography and invasive LV pressures at baseline and 5 weeks post-MI. Therapeutic hydrogels were delivered by direct intramyocardial injection (9x100 μl) at 7 days post-MI using hyaluronic acid hydrogels alone (HA-Only) (n=4) or hyaluronic acid that releases an MMP inhibitor doxycycline (HA-DOX) (n=5) into the MI region. Outcomes were compared to control MI pigs (n=7) at 5 weeks post-MI to assess therapeutic benefits. MMP inhibition was measured by uptake of the SPECT MMP targeted radiotracer,
99m
Tc-RP805 in the infarct region.

Results:
Quantitative indices of remodeling from representative PV loops are shown in Figure 1 A-C. LV end-diastolic volume (LVEDV) corrected for body weight (BW) was significantly greater in the MI-controls at 5 weeks post-MI compared to the HA-DOX group (Fig 1D, p=0.035, t-test). There was a statistically significant difference in LV end-diastolic pressure (LVEDP) (Fig 1E) between MI-controls and HA-DOX (p=0.025, ANOVA). There was a trend for decreased LV compliance (Fig 1F) in MI-controls based on the EDPVR V30. These changes correlated with a significant decrease in
99m
Tc-RP805 in the MI region of HA-DOX animals compared to controls (Fig 1G).

Conclusion:
LV PV analysis demonstrated significant adverse remodeling in control pigs that was reduced by early intramyocardial delivery of a DOX releasing hydrogel post-MI. Delivery of both hydrogels prevented some measures of adverse LV remodeling, with prevention of LV dilatation and reduction in LVEDP and correlated with a decrease in MMP activation by SPECT
99m
Tc-RP805.
Abstract 4144119: Association Between High-Intensity Exercise and Progressive Aortopathy in Patients with Bicuspid Aortic Valve
Authors: Shi Meilynn , Saleh Danish , Simons Margaret , Gerweck Kira , Baldridge Abigail , Kruse Jane , Wilsbacher Lisa , mehta chris , Malaisrie S. Christopher , PUTHUMANA JYOTHY
Published: November 2024

Background:
Individuals with aortic dilation (≥4.0cm) or aneurysm (≥4.5cm) are encouraged to avoid high-intensity sports. However, the incidence of aortic dissection in patients with bicuspid aortic valve (BAV) is low. Restricting physical activity can also impact cardiovascular outcomes.

Aims:
The impact of exercise on progressive BAV aortopathy is not well understood. This observational study examines the association of exercise intensity with change in aortic dimensions in BAV patients with aortic dilation.

Methods:
Data was collected from a prospectively enrolled BAV cohort established by the Bluhm Cardiovascular Institute (BCVI) in 2005. BAV patients with aortic diameter ≥4.0cm on CT/MRI and without prior aortic intervention were included. Activity intensity was graded based on AHA/ACC Classification of Sports. Patients who engaged in high dynamic/static component activities for ≥4 hours/week were classified as high-intensity exercisers. Those who engaged in the same activities for <4 hours/week or engaged in low static/dynamic activities or no activity were classified as less than high-intensity exercisers.

Results:
There were 65 high-intensity exercisers and 44 less than high-intensity exercisers. Median follow-up was 9 years (IQR 5.5-11.2). There were no significant differences in demographics, risk factors, or beta-blocker and statin use (Table 1). No statistically significant differences were observed in annual rate of change of the maximal dimension of the sinus of Valsalva (0.09 vs 0.19mm, p=0.15), sinotubular junction (0.12 vs 0.16mm, p=0.60), mid-ascending aorta (0.25 vs 0.24mm, p=0.88), or proximal ascending aortic arch (0.14 vs 0.21mm, p=0.21) between the two groups (Figure 1).

Conclusions:
High-intensity exercise was not associated with progressive aortic dilation in patients with BAV. This observation warrants further study of exercise restrictions in patients with BAV and aortic dilation as these may deter otherwise healthful cardiovascular behaviors.
Abstract 4144153: Artificially Sweetened Beverages and Cardiovascular Events: A Meta-Analysis of Nearly One Million Cohort Patients
Authors: Queiroz Ivo , Defante Maria Luiza Rodrigues , Barbosa Lucas , X. Mendes Beatriz , Antunes Vanio do Livramento Junior , Mazetto Roberto , Bulhoes Elisio , Silva Catarina , Romeiro Pedro , Guida Camila
Published: November 2024

Background:
With the rising use of artificial sweeteners as sugar substitutes, concerns regarding their impact on cardiovascular health have emerged. Despite approval by national food regulatory agencies, evidence of their association with clinically significant cardiovascular events remains inconclusive. This study aimed to assess this relationship through a systematic review and meta-analysis.

Methods:
PubMed, Embase, and Cochrane databases were systematically searched for cohort studies investigating the incidence of stroke, cardiovascular death (CVD), coronary heart disease (CHD), and all-cause mortality (ACM) among individuals with high consumption of artificially sweetened beverages (ASBs) compared to minimal or no consumption. Pooled event prevalence and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a random-effects model in R software, with heterogeneity assessed via I2 statistics.

Results:
After overlapping population disposal, eight cohorts comprising 917,971 patients (mean age 52 years; 67.7% female) were included. Analyses were conducted on patient groups with data adjusted for dietary factors, comorbidities, and family history of heart disease. High Consumption of ASBs was significantly associated with a higher risk of ACM (HR 1.1760; 95% CI 1.0186-1.3578, p=0,027), stroke (HR 1.2501; 95% CI 1.0555-1.4807, p=0,01) and CVD (HR 1.4722; 95% CI 1.2821-1.6905, p<0,001). There was no statistically significant association found for CHD (HR 1.1215; 95% CI 0.9280-1.3554, p=0,235).

Conclusion:
In this meta-analysis, we found a significant association between high consumption of ASBs and increased incidence of ACM, CVD, and stroke highlighting potential cardiovascular implications. Further studies with improved methodologies are needed to corroborate these findings and elucidate the underlying mechanisms.
Abstract 4144180: Preclinical Investigation of Integration and Tissue Response to a Novel Growth-Accommodating Transcatheter Pulmonary Valve
Authors: Agwu Nnaoma , Burney Tanya , Perminov Ekaterina , Alcantara Christopher , Edwards Robert , recto michael , Kheradvar Arash
Published: November 2024

Background:
Among 40,000 newborns with congenital heart defects, many face right ventricular outflow tract (RVOT) dysfunction, requiring pulmonary valve replacement. Existing options like the Melody™ transcatheter pulmonary valve aren't suitable for children under 20 kg, posing risks to the right ventricle (RV) as smaller children await weight gain. To avoid the detrimental effects to the RV in young children, we have developed IRIS Valve, a novel growth accommodating transcatheter pulmonary heart valve. This valve can be implanted using a 12-Fr transcatheter delivery system, catering to children weighing as little as 8 kg. As the native valve annulus expands, the IRIS Valve can be balloon-expanded up to 20mm.

Hypothesis:
We investigate the successful integration of the IRIS Valve into the RVOT six months after implantation.

Aims:
We aimed to assess the IRIS Valve's integration and chronic response over a six-month period in Yucatan mini-pigs to ensure the prosthetic valve's integrity.

Methods:
Derived from origami ideas, the IRIS Valve maintains its fully-coapted trileaflet design crafted from porcine pericardial tissue, in a diameter range from 12 mm to 20 mm (Fig. 1). The animal implantation studies involved seven Yucatan pigs weighing between 8 and 17 kg. The implantation was performed using a 12- or 14-Fr delivery catheter. The valves were appropriately balloon-expanded to accommodate the increasing size of the animals. Six months post-implantation, two animals were euthanized, and their hearts were harvested for histopathological analysis. The RVOT and proximal pulmonary artery, containing the IRIS Valve, were excised, stained with H&E, and embedded into MMA blocks.

Results:
All seven implanted IRIS Valves maintained precise positioning at the native pulmonary valve and exhibited either no or minimal regurgitation across pigs with diverse pulmonary annulus sizes (Fig. 2). Macroscopic examination post-euthanasia revealed intact valve leaflets. Histopathological examination with H&E staining demonstrated robust integration of IRIS Valve into the RVOT wall, accompanied by a variable chronic inflammatory response characterized by mixed lymphocytes and macrophages, as well as multinucleated giant cells reacting to both the ePFTE skirt and suture material (Fig. 3).

Conclusions:
Our findings indicate that the IRIS transcatheter pulmonary valve maintains its integrity throughout the 6-month study period and exhibits characteristic chronic inflammatory markers.
Abstract 4144226: Is it useful to wash stored red blood cells in cardiopulmonary bypass priming fluid for neonatal cardiac surgery?
Authors: Wang He , Liu Jia , Jin Yu , Liu Jinping
Published: November 2024

Background and Objectives:
Neonatal cardiac surgery requires careful consideration of cardiopulmonary bypass (CPB) priming fluid composition due to small blood volume and immature physiology. This study investigated the impact of allogeneic stored red blood cells (RBCs) processed using an autotransfusion system in CPB priming fluid for neonates.

Materials and Methods:
We compared perioperative parameters, inflammatory mediators, coagulation indicators, vasoactive-inotropic score (VIS), and clinical outcomes between neonates receiving unwashed (n=56) and washed (n=45) RBCs in CPB priming fluid. Regression models were used to assess the independent association between RBC washing and patient outcomes.

Results:
The autotransfusion system improved stored RBC quality. The washed group showed higher peak hematocrit (P < 0.01) and hemoglobin levels (P = 0.04) during CPB, an increased oxygen delivery index during rewarming (P < 0.05), and lower postoperative lactate levels and VIS (P < 0.05).Inflammatory (IL-6, IL-8, IL-10) and coagulation parameters (DD, FIB, FDP) fluctuated compared to baseline but did not significantly differ between groups. The washed group had a lower incidence of hyperlactacidemia and delayed sternal closure at CPB weaning.

Conclusions:
Adding washed allogeneic stored RBCs to neonatal CPB priming fluid reduced postoperative lactate elevation and VIS without early improvement in the inflammatory and coagulation systems.
Abstract 4144233: Left Atrial Appendage Thrombus Prediction with Statistical Shape Modeling
Authors: Mackenzie Colin , Morris Alan , Ruckel Shane , Elhabian Shireen , Bieging Erik
Published: November 2024

Introduction:
Shape of the left atrial appendage (LAA) has been proposed a predictor of stroke in patients with atrial fibrillation (AF). Prior literature employ qualitative assessments of LAA shape, which limits reproducibility. Statistical shape modeling is a quantitative method for assessment of shape. CT is increasingly utilized for identifying LAA thrombus prior to cardioversion in patients with AF. In this study we use particle based statistical shape modeling to quantify shape of the LAA, both independently and with the left atrium (LA), and evaluate if shape correlates with presence of LAA thrombus.

Methods:
We collected 132 cardiac CTs from consecutive studies of patients over 14 months obtained for evaluation of LAA thrombus prior to cardioversion. Of these, 16 patients were excluded. The LA and LAA were manually segmented independently from the systolic phase of the remaining 116 patients. Shape analysis was then performed using Shapeworks software (SCI, University of Utah) to compute shape parameters of the LAA in isolation as well as the LA and LAA in combination without controlling for scale or orientation. The shape parameters explaining the greatest shape variance were considered for the model until at least 80% of shape variance was included. A logistic regression model for prediction of LAA thrombus was created using these shape parameters with forward and backward stepwise model selection.

Results:
Of the 116 studies analyzed, 6 patients had thrombus in the LAA. Average shapes of the patients with and without thrombus differed in overall size as well as prominence of the LAA. Four shape parameters accounted for 81.2% of the LAA shape variance while six shape parameters accounted for 80.5% of the combined LA and LAA variance. The first shape parameter was predictive of LAA thrombus using both shape of the LAA only (p = 0.0258, AUC = 0.762), and when LAA shape was combined with LA shape in a joint model (p = 0.00511, AUC = 0.877).

Conclusion:
Statistical shape modeling of the LAA, with or without the LA, can be performed on CT image data, and demonstrates differences in shape of these structures between patients with and without LAA thrombus. Patients with LAA thrombus had a larger overall LAA size, LA size, and a more prominent LAA with distinctive morphology. Findings suggest that statistical shape modeling may offer a quantitative and reproducible approach for using LAA shape to assess stroke risk in patients with AF.
Abstract 4144238: Associations of neutrophil counts with risk of cardiovascular disease and all-cause and cause-specific mortality: a systematic review and meta-analysis of prospective cohorts
Authors: Wei Cheng , Tan Bohao , Li Ziyue , Feng Yu , Wang Kang , Yu Bilian , Mou Yuchan , Bramer Wichor , Zhou Shenghua , Chen Zhangling
Published: November 2024

Background and Aims:
High neutrophil counts, an easily accessible inflammation biomarker, has been linked to risk of cardiovascular disease (CVD), and mortality, but with mixed results. We aimed to summarize published associations between neutrophil counts with risk of CVD and all-cause and cause-specific mortality among generally healthy populations.

Methods:
We searched Medline, Embase, Web of Science, and Cochrane CENTRAL databases until March 2024. Random effect meta-analysis was conducted to calculate pooled risk ratios (RRs) and 95% confidence intervals (95%CIs) for highest versus lowest categories of neutrophil counts in relation to risk of CVD and all-cause and cause-specific mortality among general healthy populations. Linear and non-linear dose-response analyses were also performed.

Results:
Our systematic review and meta-analysis included 22 prospective cohort studies. During a median/mean follow-up period of 3.8 to 18.3 years, 73,934 CVD events and 80,317 deaths occurred among 1,962,191 participants. Higher neutrophil counts were associated with a higher risk of CVD incidence and all-cause mortality, CVD mortality, and non-CVD mortality. The pooled RRs (95%CIs) of highest versus lowest categories of neutrophil counts were 1.32 (1.20, 1.45) for risk of CVD incidence, 1.61 (1.23, 2.11) for all-cause mortality, 1.71 (1.45, 2.01) for CVD mortality, and 1.68 (1.17, 2.40) for non-CVD mortality. Further, per 1 SD increase of neutrophil counts was associated with a 4%, 12%, 14%, and 24% higher risk for CVD events, all-cause mortality, CVD mortality, and non-CVD mortality, respectively. In addition, a secondary dose-response analysis revealed a non-linear association of neutrophil counts with risk of CVD events (P
non-linearity
= 0.01), but a linear positive association with CVD mortality (P
non-linearity
= 0.87). The pooled associations of neutrophil counts with CVD risk, and all-cause, CVD, and non-CVD mortality did not differ by age, sex, region, and follow-up duration.

Conclusions:
Higher neutrophil counts were associated with a substantially higher risk of CVD events and all-cause, CVD, and non-CVD mortality.
Abstract 4144254: Sex Differences in the Association of Leisure Time Physical Activity and Incident Peripheral Artery Disease
Authors: Pabon Maria , Foa' Alberto , Claggett Brian , Evenson Kelly , Matsushita Kuni , Solomon Scott , Hegde Sheila
Published: November 2024

Background:
The benefit of leisure time physical activity (LTPA) in preventing peripheral artery disease (PAD) is well established. However, no prior studies have examined how longitudinal changes in LTPA during mid-life influence the risk of future PAD in men and women.

Methods:
We included participants from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 3 and were free of PAD [ankle brachial index (ABI) >0.90] with available ABI during follow-up (measured ~5, 18, and 25 years after visit 3). LTPA was assessed using the modified Baecke questionnaire and defined as ideal, intermediate, or poor by the American Heart Association. Change in LTPA from visit 1 (1987-1989) to 3 (1993-1995) was subcategorized as 1) persistently poor, 2) decreased, 3) increased, or 4) persistently active. The primary outcome of time-to-incident PAD after visit 3 (ABI ≤ 0.90), was assessed using Cox models adjusted for relevant covariates.

Results:
A total of 8,421 participants were included (mean age 59 ± 5.5 years, 56% women, 20% Black). From visit 1 to 3, 1,609 participants had persistently poor LTPA, 1,860 decreased their activity, 2,015 increased their activity, and 2,937 remained persistently active. During a median follow-up of 17.7 years, 853 ARIC participants developed PAD (471 women and 382 men). An increasing or persistently active level of LTPA was associated with lower risk of incident PAD (HR 0.74 (0.60, 0.89) p=0.003 and HR 0.71 (0.58, 0.85) p<0.001 respectively) compared to persistently poor LTPA. There was no difference between those in the decreasing LTPA category and those with persistently poor LTPA (HR 0.88 (0.72, 1.09) p=0.24). There were no interactions with race, age, or body mass index; however, there was significant effect modification by sex (p-int 0.01). Men who increased activity or were persistently active had lower risk of developing PAD as compared to those with persistently poor LTPA (
Table
). There was no association between changes in LTPA and incident PAD in women.

Conclusions:
Maintaining or increasing LTPA over six years was associated with decreased risk of incident PAD in men but not in women. Further research is needed to clarify sex differences in these associations.
Abstract 4144261: Hispanic/Latino Patients with Heart Failure with Preserved Ejection Fraction: A Participant Level Pooled Analysis of 3 Contemporary Trials
Authors: Pabon Maria , Claggett Brian , Fernandez Marcos , Makuvire Tracy , Desai Akshay , Lewis Eldrin , Jhund Pardeep , Pfeffer Marc , Pitt Bertram , McMurray John , Solomon Scott , Vaduganathan Muthiah
Published: November 2024

Introduction:
Prior studies have suggested that Hispanic/Latino patients with HFpEF in the US may have lower mortality rates than non-Hispanic/Latinos. However, few contemporary data exist examining the clinical risks faced by Hispanic/Latino patients with HFpEF, especially in global settings.

Methods:
We performed a participant-level pooled analysis of the TOPCAT (Americas region), PARAGON-HF, and DELIVER trials, including participants with symptomatic HF and an LVEF >40% (in DELIVER) or ≥45% (in TOPCAT and PARAGON-HF). Hispanic/Latino ethnicity was self-reported. The risk of the primary endpoint, cardiovascular death or HF hospitalization, was compared among Hispanic/Latino and non-Hispanic/Latino patients using Cox regression models adjusted for relevant clinical covariates, stratified by trial and region of enrollment.

Results:
Of the 12,826 participants, 2,013 (16%) were Hispanic/Latino. 71% of Hispanic/Latino patients were enrolled in Latin America, 19% in North America and 10% in Europe. Hispanic/Latino participants were less likely to have a history of atrial fibrillation (36% vs. 56%), had a higher eGFR, and had better functional status but had similar levels of natriuretic peptides as compared to non-Hispanic patients (Figure 1). During a median follow-up of 2.6 years, Hispanic/Latino participants experienced similar rates of the primary outcome (adj HR 1.12; 95% CI 0.90-1.39; p=0.29) and secondary outcomes as compared to non-Hispanic/Latinos (
Table 1 and Figure 1
). Findings were similar when including only patients enrolled in the Americas (n=4,728; adj HR 1.05; 95% CI: 0.78-1.41; p=0.77). There were no interactions with age, sex, BMI, or diabetes status.

Conclusions:
Contrary to prior reports, this pooled analysis of HFpEF participants enrolled in 3 contemporary global trials showed that Hispanic/Latino patients experienced similarly heightened risks of adverse cardiovascular outcomes and mortality as non-Hispanic/Latino patients.
Abstract 4144292: Attenuation of Black-White Disparities in Cardiovascular Disease Incidence and Total Mortality by Life’s Essential 8: Cardiovascular Lifetime Risk Pooling Project (LRPP)
Authors: Ardehali Mariam , Ning Hongyan , Wilkins John , Lloyd-Jones Donald
Published: November 2024

Background:
Higher cardiovascular health (CVH), as measured by Life’s Essential 8 (LE8) score, is associated with lower mortality and incident cardiovascular disease (CVD). It is unclear if having higher CVH attenuates racial disparities in CVD and total mortality.

Methods:
We used data from the LRPP, including the ARIC, CARDIA, MESA, and Framingham Offspring cohorts, for which LE8 scores (0-100 points, higher is better) could be calculated in participants (ppts) aged 20-59 years who self-identified as Black or White. We compared incidence rates and adjusted hazard ratios (aHR; adjusted for age, sex, and maximal education years) for incident CVD and total mortality between Black and White ppts. We estimated the quantitative reduction in Black-White hazards without vs. with adjustment for LE8 score by examining the proportional change in the beta coefficients.

Results:
Our sample included 20,618 ppts (28.6% Black; 54.8% women; mean age 45.9±11.6 years) followed for 499 000 person-years, of whom 4316 developed CVD events and 5660 died. Mean LE8 score was 66.4±14.3 for White and 61.5±14.7 for Black ppts. Among White ppts, 19.9% had a CVD event and 25.8% died, compared to 23.4% and 31.7% of Black ppts, respectively. Compared with White ppts, Black adults had higher hazards for incident CVD (aHR 1.55; 95% CI 1.54-1.56). Additional adjustment for LE8 score attenuated the HR to 1.20 (95% CI 1.12-1.29), representing a 58.1% reduction in the beta estimate for race (see
Table
). Considering LE8 metrics individually, adjustment for blood pressure score was associated with the greatest proportional reduction in the Black-White beta estimate (47.7%). Findings were overall similar for associations and attenuation of racial disparities in total mortality, with a 39.9% reduction in the beta estimate for Black vs. White ppts.

Conclusions:
In young and middle-aged adults, adjustment for cardiovascular health score partially attenuated Black-White disparities in incident CVD events and mortality. It is likely that the observed disparities are based on social and structural determinants. Improving CVH from young adulthood could be an important strategy for reducing racial disparities in CVD events and mortality.
Abstract 4144297: The Presence of Arm Pain Predicts Coronary Artery Occlusion Requiring Revascularization in Patients with NSTEMI
Authors: Dzikowicz Dillon , Lai Chi-Ju , Saoji Sankalp Babarao , Zegre-Hemsey Jessica , Devon Holli , Wang Linwei , Zareba Wojciech
Published: November 2024

Introduction:
Non-ST elevation myocardial infarction (NSTEMI) represents about 70% of ACS cases, and nearly one-third of these patients have an occluded coronary artery that may benefit from revascularization. The 13-item ACS Symptom Checklist is a validated tool designed for rapid assessment of Acute Coronary Syndrome (ACS) symptoms. We aimed to evaluate the effectiveness of the ACS Symptom Checklist in differentiating NSTEMI patients with and without an occluded artery.

Methods:
All NSTEMI patients treated at the University of Rochester Medical Center between 2015-2023 (n=3515) were included. The 13-items from the ACS Symptom Checklist were extracted using natural language processing (NLP) before coronary angiography or within 24 hours of presentation. An occluded coronary artery was one requiring revascularization with percutaneous coronary intervention. Chi-Square was used to assess the sensitivity and specificity of each symptom for an acutely occluded coronary artery. We used logistic regression models to assess the odds of an acutely occluded artery after controlling for age, obesity, and diabetes and stratified by sex.

Results:
Patients were predominantly male (58%, n=2048), older (69
+
13 years), and White (85%, n=2988), and 15% (n=524) underwent revascularization. Diabetes (18%, n=629) and obesity (40%, n=1387) were common comorbidities. Upper back pain (10.5% vs. 14.1%, p=0.03), palpitations (19.3% vs. 23.9%, p=0.02), arm pain (21.0% vs 16.7%, p=0.05), unusual fatigue (8.9% vs. 22.2%, p<0.01) significantly differentiated between NSTEMI patients with and without an occluded coronary artery as observed in Table 1. Among men, less upper back pain (OR=0.559, 95% CI 0.361-0.865), palpitations (OR=0.678, 95% CI 0.503-0.915), and unusual fatigue (OR=0.365 95% CI 0.270-0.493) were significant predictors of coronary occlusion. Only a higher likelihood of arm pain (OR=1.184, 95% CI 0.893-1.569) predicted occlusion. Results were similar for women.

Conclusion:
Only arm pain, a common symptom of ischemia, predicted an occluded coronary artery in patients with NSTEMI and there were few sex differences. NLP confirmed that the presence of arm pain can cue clinicians into the probability of ischemia in this large sample of patients. Prospective studies are needed to validate these findings.
Abstract 4144298: Structural Remodeling of Coronary Microvasculature in Hypertrophic Obstructive Cardiomyopathy
Authors: Roshdy Mohamed , Ibrahim Ayman , Soror Eslam , Azer Gayed Mina , Osman Manar , Sarathchandra Padmini , Nicastro Laura , Hayman Danika , Hosny Mohamed , Elaithy Amany , Aguib Yasmine , Terracciano Cesare , Yacoub Magdi
Published: November 2024

Background:
Microvascular dysfunction is a hallmark of hypertrophic obstructive cardiomyopathy (HOCM). Factors modulating myocardial microcirculation in response to disease phenotype require further studies. This study aims to investigate microvascular remodeling in HOCM patients using a quantitative imaging toolset that combines classical histological screening, ultrastructure assessment, 3D molecular imaging and automated segmentation of myocardial tissue specimens.

Methods:
Microvascular remodeling was studied in a cohort of 20 consecutive HOCM patients who underwent septal myectomy, and 6 normal controls. Myectomy specimens were examined using histopathological staining, immunofluorescence and electron microscopy. Molecular 3D visualization was conducted using Free of Acrylamide SDS-based Tissue Clearing (FASTClear) protocol of 300 µm thick myocardial slices. Cleared slices were examined using immunostaining targeting microvascular markers; Isolectinβ4 and CD31. Reconstructed images of stained slices were analyzed using ImageJ and Python-based algorithm. Transcriptome data from HOCM patients’ myocardial tissues was analyzed to investigate angiogenesis and hypoxia-related gene expression. Gene and protein expression was validated using RT-PCR and immunohistochemical staining.

Results:
Histopathological examination demonstrated a significant increase in perivascular fibrosis around intramural vessels in HOCM myocardial tissues, compared to controls, associated with a significant increase in vascular wall thickness, which led to a reduction in luminal area. Electron microscopy analysis revealed, for the first time, ultrastructural changes in the microvasculature in HOCM, including irregular microvessels, disorganized perivascular collagen fibres and abnormal endothelial cell morphology. Increased Aurora and Caspase 3 levels in the endothelial cells of myocardial microvessels were observed. 3D molecular imaging of myocardial slices showed a significant reduction in microvascular density, length, and number of microvascular branches in HOCM, which correlated to LVOT. Microvascular orientation was significantly altered throughout slices of HOCM myocardium. Transcriptome data analysis and protein examination revealed that angiogenesis and hypoxia-related markers elevate in HOCM patients’ myocardial tissues.

Conclusion:
Structural alterations of coronary microvasculature delineate the clinical presentation and myocardial functional response in HOCM patients.
Abstract 4144323: Does Location Matter? Comparison of Myocardial Substrate in Patients with Non-Ischemic Cardiomyopathy Undergoing Ventricular Tachycardia Ablation
Authors: Vashistha Kirtivardhan , Maan Abhishek , Newman Seth , Mirza Jacqueline , Garikapati Srilakshmi , Stanton Eric , Chadha Sakshum , Musikantow Daniel , Turagam Mohit , Koruth jacob , Whang William , Miller Marc , Lampert Joshua , Dukkipati Srinivas , Reddy Vivek
Published: November 2024

Background:
Although there is an association between scar burden and an increased risk of recurrent arrhythmic events; but there is a limited data on the location of myocardial substrate and its association with the stage of non-ischemic cardiomyopathy (NICM) assessed by left ventricular ejection fraction (LVEF).

Hypothesis:
Location and extent of arrhythmogenic scar burden in patients with NICM represent the progression of the disease.

Aim:
To evaluate: Association of location and extent of myocardial substrate (Isolated Septal vs. Septal and Non-Septal involvement) with LVEF.

Comparison of arrhythmic burden according to location of the myocardial substrate based on findings during VT ablation.

Methods:
We performed retrospective data collection in patients with NICM who underwent VT ablation procedure and stratified them according to EF of < 35% vs.
>
35%. For the initial analysis, we compared the location of myocardial substrate (Isolated septal vs. Septal + Non-Septal involvement) assessed with the use of Cardiac magnetic resonance imaging (cMRI) and electroanatomical mapping. We also compared the number of distinct mmVT morphologies induced during ablation according to the location of the myocardial substrate.

Results:
We analyzed a total of 183 consecutive patients with NICM who underwent VT ablation during the time frame of 11/2016 to 11/2023 and had cMRI with mapping data available. The mean age of patients in our study cohort was 60.9 years (IQR 53-71) and 20.7% of population were females the mean LVEF in study was 39%. Isolated septal involvement was more common in patients with LVEF
>
35% than the patients with LVEF < 35% (32.3% vs. 25.3%, p = 0.04). Despite isolated septal involvement, the total number of distinct mmVT induced during VT ablation were similar to the group with Septal + Non-septal involvement. (2.03 vs. 1.82, p = 0.22)

Conclusion:
Our results suggest a temporal involvement in the extent of arrhythmogenic substrate as in; septal involvement might represent an earlier stage in NICM patients.

Despite the finding, isolated septal involvement seemed to have an equivalent risk as an arrhythmogenic VT substrate based on the findings of distinct morphologies of mmVT induced during ablation.
Abstract 4144327: Hemodynamic and Myocardial Relevance Of Microvascular dysfunction After Elective Percutaneous Coronary Intervention.
Authors: Jallad Pedro , Maksud Danilo Maksud , Alves Bruno , Calderon Jean Carlos , GODINHO ROGER , Pileggi Brunna , Lopes Neuza , Gowdak Luis Henrique , Abizaid Alexandre , CAMPOS CARLOS
Published: November 2024

Background:
Previous research has established that a cut-off value of the index of angiographic-derived microcirculatory resistance (AMR) greater than 250 mmHg*s/m is indicative of poorer clinical outcomes in cases of primary PCI. This study aims to investigate the correlation of AMR post elective PCI > 250 mmHg*m/s in coronary flow velocity ratio (CFVR) and high-sensitivity troponin (hsT) peak.

Methods:
Between June 2021 and December 2023, a total of 330 patients with successful elective PCI and without side branch occlusion were selected for microcirculation analysis using AngioPlus Core (Shanghai Pulse Medical Technology Inc) in a tertiary cardiology hospital at São Paulo, Brazil. HsT peak, AMR and CFVR were compared.

Results:
Our patient cohort was stratified based on post PCI AMR, utilizing a threshold of 250 mmHg*s/m (Figure 1A), with 162 patients in group > 250 mmHg*s/m (mean 299.4 ± 42.5 mmHg*s/m) and 168 patients <250 mmHg*s/m (mean 214.6 ± 28.1 mmHg*s/m). The AMR > 250 mmHg*s/m group exhibited lower CFVR pre PCI (p <0.001, Figure 1B) and post PCI (p <0.001, Figure 1C), associated with a higher peak hsT (p <0.001, Figure 1D).

In relation to AMR and μFR parameters, we found higher μFR (p = 0.005, Figure 2A) in patients with CMD (AMR > 250 mmHg*s/m, figure 2A), but no statistically difference in delta μFR (p = 0.08, Figure 2B). Lower AMR pre PCI (p < 0.001, Figure 2C) and higher delta AMR (p = 0.003, Figure 2D) are associated with AMR > 250 mmHg*s/m.

Conclusion:
We demonstrate that an AMR exceeding 250 mmHg*m/s following elective successful PCI is associated with reduced coronary flow velocities and myocardial injury. These indexes have potential utility in clinical practice as risk stratification tools.
Abstract 4144346: Gender, Racial/Ethnic and Regional Differences in Trends of Stroke-related Mortality in Atrial Fibrillation: a National Database Analysis 1999-2020
Authors: Siddiqi Rabbia , Farhan Syed Husain , khuder sadik , Eltahawy Ehab , Grubb Blair , Moukarbel George
Published: November 2024

Background:
Stroke is a leading cause of death globally. Atrial fibrillation (AF) is an important modifiable risk factor for stroke. Ascertaining the burden of stroke in AF, its temporal trends and demographic disparities can inform public health policy measures.

Aims

To describe national temporal trends of ischemic stroke-related mortality in patients with AF and identify any differences by gender, race, ethnicity, or region.

Methods:
In this cross-sectional analysis we used death certificate data from the national CDC Wide-Ranging ONline Data for Epidemiologic Research (WONDER) database for adults aged 35-84 years between 1999 and 2020. We queried for both ischemic stroke and AF as contributing or underlying cause of death. Crude and age-adjusted mortality rates (AAMR) were computed for the overall population and stratified by sex, race/ethnicity, geographic region, state, and rural/urban status. Joinpoint Regression Analysis software was used for trend analysis. Average annual percentage change (APC) in AAMR were computed using log-linear regression models.

Results

A total of 32,386 ischemic-stroke related deaths occurred in patients with AF between 1999 and 2020. Overall mortality trends were stable until 2014, sharply rose between 2014 and 2017 (APC 27.6% [95% confidence interval, CI, 18.8-33.4]), slowing down between 2017 and 2020 (APC 2.48 [95% CI, -4.81-7.03]). Overall AAMR per 100,000 was higher in men (1.00 vs 0.86 in women; Figure 1); Non-Hispanic Whites (0.98 versus 0.81 in Non-Hispanic Blacks and 0.70 in Hispanics; Figure 2), individuals in the Western census region (1.07 vs 0.95 in Southern, 0.92 in Midwestern and 0.78 in Northeast regions; Figure 3) and non-metropolitan areas (1.06 versus 0.91 in metropolitan). The rate of increase in AAMR over recent years was significantly greater in Black populations.

Conclusion:
Stroke mortality in AF rose sharply since 2014. Our findings underscore racial and geographic differences that exist in stroke-related deaths in the US.
Abstract 4144372: TET2-mutant Clonal Hematopoiesis Promotes Heart Failure with Preserved Ejection Fraction
Authors: Pandey Ambarish , Thomas Toby , ji yuanyuan , Kroger Benjamin , Irion Camila , Kalkan Fatma , Segar Matthew , Subramanian Vinayak , Bayes-Genis Antoni , Hu Wenhuo , Son Albert , Young Kira , Trowbridge Jennifer , Carlsgaard Peter , Premnath Naveen , jiang nan , Daou Daniel , Ware Sarah , Chung Stephen , Tong Dan
Published: November 2024

Introduction:
Aging and inflammation are both important risk factors of heart failure with preserved ejection fraction (HFpEF). However, a potential mechanistic link between them in HFpEF pathogenesis remains unknown. Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition characterized by the clonal expansion of hematopoietic stem cell (HSCs) bearing mutations in certain driver genes and is associated with increased inflammation and elevated risk of cardiovascular diseases. However, our understanding of the role of CHIP in HFpEF remains limited.

Methods and Results:
We evaluated the prevalence and clinical impact of CHIP in two independent and well-annotated HFpEF cohorts. We compared a single-center registry of deeply phenotyped HFpEF cases at UT Southwestern with age- and sex-matched controls from the Dallas Heart Study (N=108 each), observing that the prevalence of CHIP was significantly higher in HFpEF patients as compared to matched controls (25%
vs
19%). We also discovered that
TET2
is the most frequently mutated gene in this population (63% in HFpEF
vs
40% in controls), while
DNMT3A
mutations were underrepresented (30%
vs
45%). We validated these findings in an external cohort of HFpEF patients from the TOPCAT trial (N=213). Importantly, we discovered that the presence of CHIP is independently associated increased risk of heart failure hospitalization and all-cause mortality (adjusted HR 2.07, 95% CI: 1.01-4.22, p = 0.046).

To determine whether CHIP causally links with HFpEF, mice received
Tet2
knockout (KO)
vs
wildtype bone marrow, and were subjected to a well-established “two-hit” HFpEF induction model. Despite similar systemic responses, the
Tet2
KO group manifested exacerbated diastolic dysfunction. This effect is
Tet2
specific, as mice harboring HSCs loss of
Dnmt3a
did not develop such phenotype. Bulk and single-cell RNASeq analyses revealed that HFpEF induction led to an expansion of pro-inflammatory and pro-fibrotic macrophage subsets in the heart, which was exacerbated by CHIP. There is an enrichment of NLRP3/ IL1b inflammatory genes in the
Tet2
KO group, and NLRP3 deficiency in HSCs attenuates the phenotype of
Tet2
KO-associated HFpEF.

Conclusion:
Our results reveal that TET2-mediated CHIP is highly prevalent in HFpEF patients and directly promotes HFpEF pathogenesis. CHIP status could serve as a marker for risk stratification and targeted anti-inflammatory therapies in patients with HFpEF.
Abstract 4144376: Applying artificial intelligence chatbot to increase heart disease awareness and knowledge in women
Authors: Fukuoka Yoshimi , Kim Diane , Devon Holli , Zhang Jingwen , Hoffmann Thomas , Sagae Kenji
Published: November 2024

Introduction:
Heart disease is the leading cause of death (LOCD) in women in the United States. Despite public campaigns, women's awareness of heart disease as the LCOD of death for women significantly decreased from 65% in 2009 to 44% in 2019. Significant declines were observed in Black, Hispanic, and young women.

Aims:
This pilot trial aims to evaluate the acceptability/usability and potential efficacy of the fully automated artificial intelligence (AI) HeartBot program to increase awareness and knowledge of heart attacks in women.

Methods:
In this pre-and post- trial, 102 women were asked to complete the baseline survey and then interact with the HeartBot. The HeartBot is an AI-based text-driven conversational agent, available 24 hours a day, 7 days a week, and fully automated (Figure 1). After 4 weeks of the interaction, women were asked to complete the post-survey. The primary outcomes include four questions (recognizing the signs and symptoms of a heart attack, telling the difference between the signs or symptoms of a heart attack and other medical problems, calling an ambulance or dialing 911, and getting to an emergency room within 60 minutes after the onset of your symptoms of a heart attack). Wilcoxon signed rank tests and ordinal logistic regression models were used to evaluate the HeartBot program.

Results:
The mean (SD) age was 46 (12) years; 60.6% of the sample was women with racial/ethnic backgrounds; 41.3% reported commercially available chatbot use (i.e. Siri) in the past 30 days. 88.5% of the sample completed the trial and the majority accepted HeartBot use. The mean (SD) length of the HeartBot interaction was 13 (11) minutes. Overall, the Wilcoxon signed-rank test indicated a significant increase in all outcomes of heart attack awareness and knowledge from the baseline and the post-Heartbot interaction (
p
< 0.05) (Figure 2). In the ordinal regression model, this significance of the outcomes remains even when controlling for potential confounding factors (
p
< 0.05).

Conclusion:
To the best of our knowledge, this was the first pilot trial to demonstrate the potential efficacy of the HeartBot program in the short term in women with diverse racial/ethnic backgrounds. However, a full-scale randomized controlled is warranted.