bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14303: Structural Remodeling in the Left Ventricular Myocardium Underlies Systolic Dysfunction in Myocardial Infarction
Authors: Neelakantan Sunder , Xiang Qian , Chavan Saurabh , Li Ke , Ling Xiao , Dixon Richard A , Sacks Michael , Vanderslice Peter , Avazmohammadi Reza
Published: April 2024

Introduction:
Myocardial infarction (MI) leads to myofiber death and the formation of a fibrotic scar in the left ventricular free wall (LVFW) myocardium. Acute MI induces remodeling events in the LV consisting of alterations in the architecture and biomechanical properties of the LVFW, collectively leading to LV systolic dysfunction. We implemented a multi-modality pipeline bridging architectural remodeling, LVFW passive behavior adaptation, and ventricular dysfunction in MI. We hypothesize that biomechanical remodeling of the LV serves as an important predictor of clinical outcomes in MI.

Methods:
MI was induced in rats via the ligation of the LAD artery, and hearts were harvested at five time points: pre-MI, and 1-wk to 4-wk post-MI (n=6 for each time point). Echocardiography and terminal LV catheterization were performed. LVFW specimens were harvested and subjected to biaxial testing, followed by picrosirius red staining. Histological slides were analyzed to quantify fiber architecture.

Results:
Comparisons for 3-wk MI versus control groups are reported (animal-specific results for representative rats are shown in Fig. 1). Echocardiography imaging showed a decrease in EF (84±5 vs 73±10%; p=0.053) and a decrease in ESV (0.122±0.045 vs 0.31±0.195ml; p=0.013). LV catheterization revealed a decrease in SV (50±0.86 vs 10±0.38μL; p<0.001) and an increase in peak systolic pressure (36.62±0.87 vs 44.91±0.99 mmHg; p<0.001), indicating systolic dysfunction. Biaxial testing revealed longitudinal stiffening of the LVFW at 3-wk post-MI. Scarring and a shift in myofiber orientation towards the longitudinal direction corroborated changes in the LVFW mechanical behavior in the MI group.

Conclusions:
LV systolic dysfunction in MI is significantly influenced by disruption in myofiber architecture and fiber orientation remodeling in the LVFW. Assessment of LVFW remodeling events provides important incremental information over traditional organ-level indices.
Abstract 14304: Incident Dialysis and Acute Kidney Injury Among Medicare Beneficiaries After Hospitalization for Heart Failure in the US
Authors: Vaduganathan Muthiah , Greene Stephen J , Patel Ravi B , Zhang Shuaiqi , Chiswell Karen , Devore Adam D , Butler Javed , Heidenreich Paul A , Huang Joanna , Kittleson Michelle M , Joynt Maddox Karen E , McDermott James J , Owens Anjali T , Peterson Pamela , Solomon Scott , Vardeny Orly , Yancy Clyde , Fonarow Gregg C
Published: April 2024

Background:
Recent therapies in heart failure (HF) have been shown to slow kidney disease progression, yet the trajectory of clinically relevant kidney events in real-world HF care is not well described.

Methods:
We identified Medicare beneficiaries hospitalized for HF at 240 US sites in the GWTG-HF registry in 2016 who did not require dialysis prior to or during hospitalization and followed them through 1-year post-discharge for incident kidney events, all-cause and HF readmissions, and death. Associations between discharge CKD-EPI-derived eGFR and time-to-first events were modeled adjusting for demographics, medical history, LVEF, discharge vital sign and laboratory measures, and hospital characteristics.

Results:
Among 20,927 Medicare beneficiaries (age 81±9y; 53% women; 10% Black), discharge eGFR was ≥90, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m
2
in 4%, 27%, 23%, 25%, and 21%, respectively. By 1 year, 37% had died and 65% were readmitted (including 31% for HF, 7% for AKI, and 5% for dialysis/end-stage kidney disease [ESKD]). Lower discharge eGFR (per 10 mL/min/1.73 m
2
decrease) was independently associated with increased mortality (aHR 1.08[1.05-1.10]), all-cause readmission (aHR 1.04[1.02-1.06]), HF readmission (aHR 1.09[1.06-1.12]), readmission for AKI (aHR 1.20[1.15-1.25]), and progression to dialysis/ESKD (aHR 2.22 [1.93-2.55]); all P<0.001. Categorical analyses consistently demonstrated heightened risks of HF and kidney events at lower eGFR. A potential J-shaped relationship was observed for mortality & dialysis/ESKD.

Conclusions:
Older adults hospitalized for HF face broad post-discharge risks of recurrent HF events, kidney events, and death. One in 20 Medicare beneficiaries are estimated to progress to dialysis/ESKD within 1-year of hospital discharge. These data may inform shared decision-making and highlight the need to prioritize comprehensive HF care that simultaneously improve outcomes in diverse disease pathways.
Abstract 14309: Clinical Outcomes of Acute Myocardial Infarction in Hematological Cancers
Authors: KHAN MUHAMMAD ZUBAIR , Weinstock Joshua , Patel Kirtenkumar , Franklin Sona , Naftulin Jason , Jamil Ayesha , Abraham Aida , Kutalek Steven
Published: April 2024

The purpose of our study is to determine hospital outcomes of acute myocardial infarction (MI) with hematological cancers and their subtypes.

Method:
Patient data was obtained from the Nationwide Inpatient Sample (NIS) database between years 2009-2015. Patients with a diagnosis of acute MI [non-ST segment elevation myocardial infarction and ST segment elevation myocardial infarction (NSTEMI/STEMI)] and hematological cancer subtypes were identified using validated International Classification of Diseases, 9th revision, and Clinical Modification (ICD-9-CM) codes. Statistical analysis using Pearson chi-squared test was performed to determine hospital outcomes between acute MI and hematological cancer subtypes.

Results:
The prevalence of NSTEMI was 1.2%, and STEMI was 0.2% in hematological cancers, n=3,027,800. Among hematological cancer subtypes, the highest prevalence of NSTEMI and STEMI was seen in lymphocytic leukemia (2.4% and 0.25%, respectively). Mortality (16.8% vs. 8.8%), hospitalization cost (25469$ ± 36763$ vs. 20534$ ± 24767$) and length of stay (8.3 days ± 10 days vs. 6.3 ± 7.8 days) were higher in the acute MI patients with hematological cancers compared to acute MI patients without cancer. Among hematological cancer patients with acute MI, the highest mortality was found in patients with myeloid leukemia (23%) followed by multiple myeloma (MM) (17.9%), lymphocytic leukemia (15.9%) and lymphoma (14.4%). The length of stay and hospitalization cost was highest in those with myeloid leukemia followed by MM, lymphocytic leukemia and lymphoma.

Conclusion:
This study showed that hematological cancer patients with acute MI had a higher mortality, hospitalization cost and length of stay. Among the hematological cancer subtypes, the highest mortality, length of stay and hospitalization cost was found in myeloid leukemia.
Abstract 14310: Anti-GM-CSF Monoclonal Antibody Gimsilumab Improved Ventilator-Free Survival, Decreased Hospitalization Length, and Prevented NT-proBNP Rise in Invasively Ventilated Patients With Hyperinflammatory COVID-19 Pneumonia: A Subgroup Analysis From the Breathe Trial Suggests Neurohormonal Role for GM-CSF Inhibition
Authors: Gottlieb Robert L , Lang Frederick M , Criner Gerard J , Mathews Kusum S , Wang Tisha S , Rice Todd W , Madduri Deepu , Lowry Simon
Published: April 2024

Background:
Granulocyte-macrophage colony-stimulating factor (GM-CSF), a myeloid cell growth factor and pro-inflammatory cytokine, may drive the overactive host immune response in COVID-19. We conducted a clinical trial assessing the anti-GM-CSF monoclonal antibody gimsilumab for hyperinflammatory COVID-19 pneumonia (BREATHE). Here, we report a pre-specified subgroup analysis demonstrating a signal of benefit in patients invasively ventilated at baseline.

Methods:
BREATHE (NCT04351243) was a double-blind, randomized, placebo-controlled trial at 21 US locations. Patients were randomized 1:1 to receive two doses of IV gimsilumab or placebo one week apart. The study included hospitalized COVID-19 patients with hyperinflammation (CRP ≥50 mg/L or ferritin ≥1,000 ng/mL) and pre-ARDS lung injury or ARDS. The primary endpoint was all-cause mortality at day 43, and key secondary outcomes assessed ventilator use and hospitalization length.

Results:
225 patients were randomized and dosed. 41 patients were invasively ventilated at baseline. Steroid use and baseline characteristics were generally balanced across study arms in this subgroup. Ventilated patients treated with gimsilumab demonstrated improvements over placebo on the primary and key secondary endpoints (Table 1). Contrasting the placebo group, gimsilumab-treated patients did not experience a sharp rise in NT-proBNP, a marker of heart failure, through day 43 (Figure 1).

Conclusions:
GM-CSF inhibition may be therapeutic in ventilated COVID-19 patients through a neurohormonal mechanism. More studies are needed to assess the role of GM-CSF in COVID-19-associated cardiomyopathy, volume status, and ARDS.
Abstract 14317: Left Ventricular Free Wall Adaptations in Heart Failure With Preserved Ejection Fraction: Insights From a Murine Model
Authors: Keshavarzian Maziyar , Neelakantan Sunder , McAlister Lilly , Leatherman Abby , Frazier Sarinity , Tong Carl W , Avazmohammadi Reza
Published: April 2024

Introduction:
Heart failure with preserved ejection fraction has heterogeneous causes. Understanding the cause of diastolic dysfunction can help with pairing correct treatment.

Hypothesis:
We hypothesize that one can elucidate the underlying cause using echocardiography.

Methods:
We performed echocardiography on hearts of cardiac myosin binding protein-C phosphorylation deficient mouse t3SA vs. its control tWT at 3 months of age with both sexes (n=6 for each group). Left ventricular free wall (LVFW) specimens were harvested and biaxially stretched along circumferential and longitudinal directions, followed by picrosirius red staining. Fiber architecture was quantified by analyzing histology images.

Results:
t3SA hearts demonstrated hypertrophy (see Fig. 1a-b for representative mice) and diastolic dysfunction (slowed e’ and increased E/e’ ratio; see Table 1). t3SA LVFW specimens showed increased longitudinal stiffness (p<0.05 for strains >0.25; Fig. 1c-d). Consistent with this stiffening, t3SA specimens exhibited pronounced fiber orientation towards the longitudinal direction (see Fig. 1e-f for representative mice). The smaller e’+S showed that t3SA mice had slowed cross-bridge cycling rates. Biomechanical analyses indicated that LVFW myocardial adaptations contributed to diastolic dysfunction.

Conclusions:
Echocardiography indices can be used to noninvasively infer underlying remodeling events contributing to diastolic dysfunction facilitating remodeling-targeted therapy selection.
Abstract 14324: Low Pulmonary Venous Flow Drives Cpc-PH Development in a Pulmonary Venous Banding Swine Model of Cpc-PH
Authors: Allen Betty , Tabima Martinez Diana Marcela , Hacker Timothy A , Seiter Daniel , Oechtering Thekla , Wieben Oliver , Chesler Naomi C
Published: April 2024

Introduction:
Combined pre- and post-capillary pulmonary hypertension (Cpc-PH) is the most severe form of PH-LHF. While the impact of elevated left atrial and consequently elevated pulmonary venous (PV) pressure on Cpc-PH progression is well studied, little is known about how compromised PV flow secondary to LHF affects disease progression. To assess the hypothesis that decreased PV flow induces Cpc-PH, we developed a large animal model of Cpc-PH by decreasing PV flow independent of LHF.

Methods:
Survival pulmonary venous banding (PVB) surgery was performed on a large white male pig (9kg), which was then followed for 16 weeks. A pig of the same sex and weight underwent a sham operation as control. Both animals underwent cardiac 4D flow MRI and right heart catheterization (RHC) in a terminal study.

Results:
At 16 weeks post-surgery, MR imaging demonstrated that PVB decreased mean flow and peak velocity in the right (RIPV) and left inferior pulmonary veins (LIPV) and MPA (figure and table). PVB also decreased MPA relative area change (RAC) (table). RHC demonstrated elevated PCWP, mPAP, PVR, and decreased RV EF (table). Also, Fulton index was increased demonstrating RV hypertrophy (table).

Discussion:
In conclusion, this study utilized PVB to demonstrate the ability of decreased PV flow to drive Cpc-PH development in the absence of LHF. Our preliminary data suggest a low flow state in the lung can increase RV afterload and induce RV dysfunction. Further studies with a larger sample size are needed to confirm this pathomechanical mechanism.

Figure. MRI image of PV confluence narrowing from the PVB. Insert shows flow rates from RIPV and LIPV (blue), across PVB (red), and into LA (green).
Abstract 14330: Contraction-Relaxation Coupling is Unaltered by Heart Failure Status in Human Myocardium
Authors: Fazlollahi Farbod , Huang Amanda , Yavornitzky Nick , Wang Anna , Peczkowski Kyra , Saad Nancy , Mashali Mohammed , Hare Austin , Campbell Courtney M , Whitson Bryan , Mokadam Nahush , Janssen Paul M
Published: April 2024

The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether these phases are linked in human myocardium is not well understood. Prior investigations have shown that the structural and biochemical myocardial remodeling secondary to exercise training and/or myocardial infarction does not disrupt contraction-relaxation (CR) coupling in the canine model system. In addition, in a wide variety of murine transgenic models targeting EC coupling, the coupling between contraction and relaxation was unaltered. Given the vast differences between inbred animal models and the human population, we investigated whether contraction and relaxation are also coupled in human myocardium, and if so, whether that coupling is affected by heart failure disease status. We retrospectively analyzed data from contractility measurements taken under conditions closely mimicking those in vivo and calculated the correlation between the maximal speed of contraction and the maximal speed of relaxation in human ventricular multicellular preparations. We categorized our data based on heart failure status as follows: non-heart failure, heart failure with ischemic cardiomyopathy, or heart failure with non-ischemic cardiomyopathy. In every case isolated right ventricular trabeculae and/or left ventricular trabeculae (n=53 subjects LV and RV analyzed, 38 subjects only LV, 27 subjects only RV) were isolated from freshly explanted human hearts. Multicellular preparations were then electrically paced at different muscle lengths, frequencies, and with increasing β-adrenoceptor stimulation. In all conditions, contraction and relaxation were very tightly linearly correlated regardless of disease category (typical R
2
of >0.98). While the mechanism governing this coupling is unknown, based on data form this study and past studies, we posit that CR-coupling is a fundamental myocardial property that resides in the structural arrangement of proteins at the level of the sarcomere at the basis of cross-bridge cycling.
Abstract 14338: Mitochondria-Targeted ROS Scavenger JP4-039 Induces Coronary Angiogenesis in Ischemic Myocardium Resulting in the Improvement of Cardiac Function in Post-MI Animals
Authors: Brinck Teixeira Rayane , Karbasiafshar Catherine , Tucker Aja , Raj Sidharth , Sabra Mohamed , Sellke Frank W , Wipf Peter , Abid Ruhul
Published: April 2024

Introduction:
A reduction of mitochondrial reactive oxygen species (mito-ROS) has been sought as a potential approach for recovering energy supply and improving cardiac function in cardiovascular disease. Here, we evaluated JP4-039, a mito-ROS scavenger, for post-myocardial infarction (MI) recovery.

Hypothesis:
We hypothesized that mitochondrial antioxidant JP4-039 will induce coronary angiogenesis and improve post-MI cardiac function in mice.

Methods:
FVB mice (n=8/group) underwent MI surgery and were assigned to either vehicle (sunflower seed oil) or JP4-039 group (1mg/kg, i.p., 3x/week for 4 weeks). A SHAM surgery group received vehicle only. Left ventricle (LV) ejection fraction (EF), fractional shortening (FS), and fractional area change (FAC) were assessed by echocardiography 28 days post-MI. Capillary (CD31 antibody) and arteriole density (α-SMA antibody) were quantified by immunofluorescence of ischemic heart sections 28 days post-MI. Western blot of myocardial homogenates was conducted to evaluate activation of Akt, ERK1/2, and AMPKα. Data were analyzed by One-way ANOVA and Tukey’s post-hoc, and a p value <0.05 was taken as significant.

Results:
Mice treated with JP4-039 presented with a 35% decrease in infarction size, and a 57% increase in EF compared to the vehicle group (43.6±5.1 vs. 27.8±5.3). FS and FAC of JP4-039-treated mice increased by 65% (21.9±2.9 vs. 13.3±2.6) and 90% (38.0±5.6 vs. 20.0±4.0), respectively. In ischemic myocardium, the JP4-039 group showed an increase in capillary density of 39% in comparison to vehicle (208.6±21.7 vs 149.9±18.0). Interestingly, arteriogenesis was decreased in ischemic myocardium by 31% in JP4-039-treated mice compared to vehicle group (9.0±1.1 vs. 13.1±1.5). Although activation of Akt or ERK1/2 signaling were unchanged, p-AMPKα was decreased by 67% in JP4-039 vs. vehicle (0.39±0.07 vs. 0.65±0.03) in myocardium.

Conclusions:
The findings suggest that mitochondrial antioxidant JP4-039 improves capillary angiogenesis in ischemic myocardium, resulting in improved cardiac function in post-MI mice. Mechanisms involved in differential levels of capillary and arteriole densities in ischemic myocardium are being examined in human coronary ECs and will be presented at the meeting.
Abstract 14362: Retention of CD34+ Progenitor Cells in the Coronary Circulation Correlates With Insulin Levels Depending on Insulin Resistance
Authors: Ozcan Ilke , Toya Takumi , Ahmad Ali , Nardi Valentina , Rajai Nazanin , Lerman Lilach , Lerman Amir
Published: April 2024

Introduction:
Diabetes mellitus and insulin resistance are associated with accelerated vascular injury and progression of coronary atherosclerosis. CD34
+
progenitor cells are mobilized and recruited to repair the endothelial and vascular damage.

Hypothesis:
We hypothesized that the interaction of insulin levels and retention of CD34+ progenitors in the coronary arteries will be different between patients with and without insulin resistance.

Methods:
In patients with no obstructive coronary artery disease (NOCAD: <40% angiographic stenosis), blood samples were collected concurrently from the proximal aorta and the coronary sinus, and CD34+ cells counted using flow cytometry. CD34+ cells gradient was calculated by subtracting aortic from coronary sinus cell counts, with a higher gradient reflecting lower retention. Patients on antidiabetic medications were excluded. Insulin resistance (IR) was estimated as HOMA-IR index ([insulin]*[glucose]/405)) ≥2.

Results:
Of 128 patients (mean age 51±11 years, 77% females), 60 (47%) had IR (mean age 51±10 years, 73% females) and 68 (53%) did not (mean age 50±13 years, 79% females). The groups did not differ in age, sex or LDL cholesterol. The IR group had higher BMI and triglyceride levels and lower HDL cholesterol. CD34
+
cell gradient correlated directly significantly with insulin levels in patients without IR (r=0.25, p=0.04)
(Fig1A)
, but inversely in those with IR (r=-0.39, p=0.01)
(Fig1B)
. Both associations remained significant after adjustment for age, sex, and BMI (IR: r=-0.39, p=0.02; no IR: r=29, p=0.04).

Conclusions:
In NOCAD patients with IR, higher levels of serum insulin were associated with increased retention of CD34
+
cells in the coronary arteries. The current study supports a potential role for CD34
+
cells for vascular repair in patients with IR.
Abstract 14373: Artificial Intelligence for COVID-19 Chest X-rays: Early Detection of COVID-19 Pneumonia and Prediction of Patient Prognosis
Authors: Aquino Gilberto J , Chamberlin Jordan , Baruah Dhiraj , Kabakus Ismail , Leaphart Nathan , Paladugu Namrata , Mulji Anand , Nance Sophia , Fitzpatrick Logan , Fiegel Matthew , Brady Sean , Hoelzer Philipp , Zimmermann Mathis , Schoepf Joseph , Burt Jeremy R
Published: April 2024

Introduction/Hypothesis:
To validate an AI algorithm for rapid detection of COVID-19 pulmonary complications and prediction of negative 30-day outcomes in COVID-suspicious patients.

Methods:
We included 2000 chest X-rays (CXR) from patients who had a COVID-19 RT-PCR test within 14 days of the CXR. A deep learning CNN (AI-RAD Companion, Siemens) previously trained for non-COVID pneumonia was used to analyze the CXRs. A total of 1544 CXRs were first used to train the AI with COVID cases. Then, a randomized modified internal holdout of 456 patients (236 positive, 220 negative) were used as test cohort. AI results detect the presence of COVID-19 lung disease (CLD) and also report a 1 to 10 AI severity score. Positive RT-PCR within 14 days of the CXR was used as the ground-truth for COVID diagnosis. Radiologic assessment by three cardiothoracic radiologists was used to detect the presence of CLD and generate a 1 to 10 expert severity score. All-cause mortality within 30 days of the CXR was recorded. Receiver-operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was reported. Concordance metrics included intraclass correlation coefficient (ICC) for comparison of AI and expert results.

Results:
In COVID+ patients, AI demonstrated a sensitivity of 99% (205/207) , specificity of 62% (18/29), PPV of 95% (205/216), and NPV of 90% (18/20), for the detection of CLD. Amongst COVID+ patients, the AI severity score had excellent agreement with the expert severity score for lung involvement (ICC=0.89, 95% CI 0.86-0.92). There were 70 deaths in the test cohort (15.3%). The AI severity score had an excellent ability to predict all-cause mortality (AUC=0.832 vs expert AUC=0.844, p >0.05).

Conclusions:
This CXR AI tool had an excellent sensitivity for detection of COVID-19 lung disease in PCR-positive patients and excellent correlation with expert analysis. AI severity score was able to strongly predict 30-day patient all-cause mortality.
Abstract 14377: The Role of Allometric Scaling in the Association Between Professional Playing Career and Aortic Root Diameter Among Retired NFL Players
Authors: Smith Genevieve E , Fernandez Camilo , Stewart Gregory W
Published: April 2024

Introduction:
While there is concern that participation in certain elite-level sports may increase risk for aortic dilation, clinical assessment of aortic root diameter (ARD) in professional athletes remains difficult owing to the lack of available normative data proportionate to anthropomorphic variables, which further complicates proper assessment of aortic disease during the post-professional life when risk factors may be greater. Thus, we examined the effect of allometric scaling on the association between ARD and professional football career length (NFLYrs) or playing position in retired National Football League (NFL) players.

Methods:
This cross-sectional study included 1,328 retired NFL players (mean age 53.1 ± 12.7 yrs; 54.6% Black) that participated in NFL Player Care Foundation health screenings. Two-dimensional echocardiogram was used to determine ARD at the sinus of Valsalva and indexed to body surface area (BSA)
0.6
(aortic root index; ARI). Multivariable-adjusted linear regression models were utilized to examine the association of playing position group and NFLYrs with ARD or ARI, after adjusting for traditional cardiometabolic risk factors.

Results:
The mean ARD and ARI of this study cohort were 33.0 ± 6.4 mm and 19.5 ± 3.8 mm, respectively. In regression models, NFLYrs was not associated with either ARD (B: -0.04, standard error [SE]: 0.04,
p
= 0.3496) or ARI (B: -0.03, SE: 0.03,
p
= 0.3177). Conversely, increasing ARD was associated with both Big (B: 1.12, SE: 0.53,
p
= 0.0340) and Big Skill (B:1.10, SE: 0.45,
p
= 0.0144) position groups, although this was attenuated to non-significance by allometric scaling of ARD (Big, B: -0.25, SE: 0.32,
p
= 0.4303; Big Skill, B: 0.22, SE: 0.26,
p
= 0.3978).

Conclusions:
NFLYrs was not associated with increasing ARD or AIH, suggesting that a longer professional football career did not potentiate larger aortic root size later in life. While football playing position was associated with increasing ARD, this association became non-significant upon indexing of ARD to BSA
0.6
, suggesting that allometric scaling may be necessary to appropriately assess aortic root diameter in these individuals. This underlines the need for further studies examining optimal allometric scaling methodologies in this population.
Abstract 14388: Efficacy of Intravenous Procainamide for Treatment of Tachyarrhythmia in Children
Authors: Przybylski Robert , DeWitt Elizabeth S , Chu Esther , Gauvreau Kimberlee , Triedman John K , Kheir John N , Dionne Audrey
Published: April 2024

Introduction:
The safety and efficacy of IV procainamide is well established in adults, however data in pediatrics is more limited.

Methods:
Prospective cohort study including children <18 yrs old who received IV procainamide for supraventricular tachycardia (SVT) or junctional ectopic tachycardia (JET) from June 2020 to May 2021. A severity of arrhythmia score (SAS, table), including arrhythmia density score (ADS), hemodynamic severity and need for adjunctive antiarrhythmic therapy was calculated pre and post procainamide. Full success was defined as decrease of the ADS to 0 and partial success as decrease by ≥50%.

Results:
Fifty-three patients (6.9 [IQR 1.2-34.9] months) received IV procainamide for treatment of SVT (n = 25, 47%) or JET (n = 28, 52%), including 44 (83%) with congenital heart disease (CHD) and 39 (74%) following cardiac surgery. Fifty (93%) patients were given a bolus (median 5 mg/kg, range 2.5-13 mg/kg) and 52 (96%) received an infusion (median 20 mcg/kg/min, range 10-30 mcg/kg/min). Full success was observed in 28 (53%) patients, partial success in 13 (25%) and failure in 12 (23%); 7 (19%) patients required adjunctive IV antiarrhythmic therapy. Median SAS decreased from 6 (IQR 4-8) to 1 (IQR 1-5) following procainamide. Procainamide bolus >5 mg/kg was associated with greater decrease in SAS (median decrease 5 [4-6] vs 2 [0-4], p = 0.04). Children with CHD (median decrease 1 [IQR 0-4] vs 4 [IQR 4-5], p = 0.04), those in the early post-operative period (median decrease 2 [IQR 0-4] vs 4 [IQR 4-5], p = 0.03) and those with JET (median decrease 2 [IQR 0-4] vs 4 [IQR 2-5], p = 0.04) had less improvement in SAS score with procainamide.

Conclusions:
IV procainamide is effective for treatment of SVT and JET in children, and associated with decreased SAS even in patients without complete rhythm control. Higher procainamide bolus dose should be considered for increased efficacy. Future studies are needed to identify optimal doses in pediatrics.
Abstract 14392: Progression of Coronary Artery Calcium Score Predicts Higher Risk for Coronary Revascularization
Authors: Coy Kevin , singh Aditya , Petrasko Mark , Pham Melissa , Petrasko Phillip , Rynders Beatrice , Sjovold Alexander , Stys Patryk , Stys Veronica , Singh Komaldeep , Saad Shaukat Muhammad Hamza , Varga Zoltan , Hajek Catherine , Sincan Murat , Petrasko Marian S , Stys Adam , Stys Tom
Published: April 2024

Introduction:
The Coronary artery calcium (CAC) score is a powerful independent screening tool for coronary artery disease (CAD). Elevated CAC score has been significantly associated with increased rates of revascularization, however monitoring the progression of disease with a serial CAC score remains controversial.

Hypothesis:
The progression of the CAC score predicts the need for coronary revascularization.

Methods:
Data were analyzed retrospectively of patients who underwent two calcium scans between February 2008 and April 2021 as part of the Sanford Cardiovascular Prevention Program and were categorized into low (<100), moderate (100-399), or high ≥400) CAC groups. Progression of the CAC score between two scans was analyzed and the need for clinically indicated revascularization (PCI vs CABG) was evaluated by the chi-square test.

Results:
A total of 5809 subjects were screened for CAC score. 54.3% were females and the mean age was 55.6 ±10.35 years. Progression of CAC score (Low to moderate/high, moderate to high) and need for revascularization was statistically significant (P<0.001). In our study, patients who progressed from low to high and moderate to high CAC score category were found to have the highest rates of coronary revascularization, 11.92%, and 13.36 % respectively.

Conclusions:
In our study, patients who progressed to a high CAC score category were found to have a significantly increased need for revascularization. Repeating a CAC score in low to moderate risk patients may have clinical benefit and needs further investigation.
Abstract 14394: Cardiovascular Toxicities After Chimeric Antigen Receptor T-cell (CAR-T) Therapy: A Single Center Experience
Authors: Dalal Prarthana , Patel Nikita , Cascino Gregory , Sinha Arjun , Sunderraj Ashwin , Feinstein Matthew J , Akhter Nausheen
Published: April 2024

Introduction:
Chimeric Antigen Receptor (CAR)-T cell therapy has shown improved response rates in relapsed and refractory B-cell malignancies, but has been associated with adverse cardiac events. We investigated the correlation between pre-existing clinical factors and CAR-T cell therapy-related adverse cardiovascular (CV) events.

Methods:
Adult patients undergoing CAR-T cell therapy at Northwestern Memorial Hospital between 2016 and 2020 were identified. A comprehensive retrospective chart review was performed. CV events including CV death, new/worsening cardiomyopathy, and new/worsening arrhythmia were identified. Grade 2 cytokine release syndrome (CRS) with associated hypotension was a secondary outcome.

Results:
75 patients (mean age 64 years) were identified. CV events occurred in ten patients (13%; mean age 71 years). One patient had CV death, 3 patients had new/worsening cardiomyopathy, and 6 patients had new/worsening arrhythmias. Eighteen patients with grade 2 CRS and hypotension were identified. Baseline characteristics differed between patients with vs. without post-therapy CV events (Table 1). Of the 11 patients with elevated post-infusion BNP, 6 experienced a CV event after CAR T-cell therapy (55%), whereas only 2 of the 16 patients without an elevated BNP had therapy-related cardiac events (13%; p-value = 0.03). Of 9 patients with pre-existing CAD, 3 experienced a CV event after CAR T-cell therapy (33%), whereas only 7 of the 66 patients without pre-existing CAD had CV events (11%; p-value=0.09).

Conclusions:
Patients with post-infusion elevation in BNP may have increased risk for CV adverse events following CAR-T cell therapy. Increased age and pre-existing CAD may also increase risk of CAR-T cell cardiotoxicity. Clinical factors predisposing to CAR-T cell therapy-related CV toxicity merit further investigation with larger sample sizes and prospective studies.
Abstract 14406: The COVID-19 Pandemic Impact on Daily Activity and AF Burden in TRIM-AF Clinical Trial Patients
Authors: Lin Cheryl , Sun Han , Barnard John , Varma Niraj , Van Wagoner David R , Chung Mina K
Published: April 2024

Introduction:
The COVID-19 pandemic presented an unexpected intervention to examine the association between activity and AF in patients enrolled in the TRIM-AF (Targeting Risk Interventions and Metformin for AF) clinical trial, which collects daily activity and AF burden through implanted devices.

Hypothesis:
We tested the hypotheses that: 1) daily activity reduction during the pandemic, compared to pre-pandemic matched periods, can be detected by implanted devices; and 2) activity reduction was associated with increased daily AF burden.

Methods:
Daily AF burden (%) and active minutes were obtained from manufacturers for 45 subjects (28 male, 17 female, mean age 69.5 years) enrolled in the TRIM-AF 2x2 randomized clinical trial of metformin and lifestyle/risk factor modification in patients with pacemakers/defibrillators (NCT03603912). We defined pre-pandemic and pandemic matched months for each subject, maintaining constancy of pre- vs post-randomization periods and fit a linear mixed model, including age, sex, and pandemic periods, to compare the pre- and during pandemic periods (Figure A).

Results:
Mean daily active minutes decreased during the pandemic from 148.6 to 144.4 mins (mixed model p =<1E-10). Mean daily AF burden increased during the pandemic from 6.0 to 8.3 (mixed model p= 3.7E-14). Both mean values were compared to matched pre-pandemic time after adjusting for sex, age, and race. AF burden % was associated with age (median AF burden increased by a factor of 1.06/year of age, mixed model p= 1.38E-02) as expected. AF daily duration percent was negatively correlated with the daily active minutes as seen by the Kendall's rank correlation tau is -0.037 (z = -7.6232, p-value = 2.474e-14).

Conclusions:
The data suggests that activity decreased and device-detected AF burden increased during the pandemic. Further analyses could compare results to historical trends within these patients.
Abstract 14443: Deep Learning to Identify Atrial Fibrillation Phenotypes in Individual Patientsbased on Rate, Variability, Electrogram Shape
Authors: Deb Brototo , Rogers AJ J , Ganesan Prash , Alhusseini Mahmood , Narayan Sanjiv M , Rodrigo Miguel
Published: April 2024

Introduction:
Automatic identification of atrial fibrillation (AF) from Flutter or Tachycardia (AFL/AT) is key to therapy, yet devices often group them as ‘high-rate events’.

Hypothesis:
We hypothesized that (a) convolutional neural networks (CNN) may separate AF from AFL/AT better than Electrogram (EGM) rate or rhythm, and (b) The physiology represented by CNN could be probed using novel methods including computer modelling.

Methods:
We developed custom CNN on N= 450,960 EGM tracings (4 sec), in 110 patients with AF(n=55) or AFL/AT (n=55) at ablation (31.8% female, 65±11Y). Training used 88 patients; validation used 22. We systematically probed CNN with 140,360 EGM sequences controlling rate (cycle length, CL), beat-to-beat variability (%) or shape (autocorrelation, %) (figs A-B) alone or in combination.

Results:
CNN differentiated AF from AFL with a c-statistic of 0.95. Individual variations in rate (N=572), CL variability (N=418), shape (N=462), or in combination (N=26,620) decreased the c-statistic of the CNN predictions to 0.66, 0.84, 0.88, 0.58 (
P
<0.05, Delong test) respectively, suggesting rate as the primary determinant of CNN decision (Figure 1, C).

Conclusions:
Machine learning of intracardiac EGMs separates AF from AFL/AT significantly better than electrogram rate, regularity or shape. Opening the ‘black-box’ of CNN showed that additional indices from Electrograms identify the physiology of AF in individual patients. Studies on the physiological signatures for AF between patients may identify important clinical phenotypes.
Abstract 14445: Quality Assessment of Transcatheter Aortic Valve Replacement Meta Analysis: Is It Worth Reading?
Authors: sattar yasar , Song David , Riasat Maria , Singh Gurpal , Shah Rajendra , Elgendy Islam Y , Mehmood Anoosha , Mir Tanveer , Zghouzi Mohamed , Ullah Waqas , Alam Mahboob , Khan Anees , Alraies M C
Published: April 2024

Introduction:
Multiple meta-analyses have been performed since Transcatheter Aortic Valve Replacement (TAVR) and quality of the rapidly publishing data on TAVR is debatable.

Methods:
Descriptive statistics was performed on pooled samples of quality assessment statistics including heterogeneity I2, Q-statistics ,Tau, and Cochrane. An approach to high heterogeneity was reviewed in this meta-analysis to review the quality of content published online. We reported total n, average numbers and percentages. Continuous data with normal distribution was reported as mean with standard deviation (SD).

Results:
A total of 231 meta-analyses done on TAVR were included in our study. The total of 1365 outcomes were reported in all of the meta-analyses. The total outcomes with heterogeneity I2< 75% and I2 >75% were 1125 and 244 respectively. The average number of outcomes with I2 <75% was 5, while the outcomes with I2>75% was 1.19. Tau, H statistics, and Cochrane statistics were reported for 79, 1 and 42 outcomes respectively. The subgrouping was performed in 87 outcomes. The mean number of subgroups was 1 ± SD 0.06, Odds ratios, relative risk and standard mean difference were used as an effect size in 93, 63, and 36 studies respectively. The random effect model, fixed effect model, or combine models were used in 180, 67, and 53 outcomes respectively. Sensitivity analysis was performed in 109 outcomes. Meta-regression was performed in 55 outcomes with an average of 0.27 studies. 46 outcomes were able to report I2<75% after meta regression, and subgroup analysis. Trend (n) of outcomes with heterogeneity I2>75% across different studies is shown in figure 1.

Conclusion:
TAVR heterogeneity was high in up to 18% of meta analysis outcomes in all meta analysis performed. Meta regression was performed in 22% with high heterogeneity, and 18% of the outcomes were able to fix the high heterogeneity in the data.
Abstract 14460: Mitochondrial Dysfunction is Involved in Diabetic Cardiomyopathy
Authors: Xu Frank , Ho Li-Lun , Lu Tzongshi
Published: April 2024

Introduction:
Diabetes is a strong risk factor not only for cardiovascular disease (CVD) but also for the development of chronic kidney disease (CKD) and represents a large and threatening public health challenge. We previously reported the deficiency of heat shock proteins and translocase of inner mitochondrial membrane (TIM) proteins are involved in the pathogenesis of hypertensive and uremic cardiomyopathy.

Hypothesis:
In this study, we further study the mechanism of mitochondrial dysfunction in the development of CVD and diabetic cardiomyopathy in CKD.

Methods:
Commercially available primary human atrial and ventricular cardiac myofibroblast and primary human aortic endothelial cells from 3 different age-matched sources were used in our type 2 diabetic cell model, in vitro. Immunohistochemistry, western blotting, Next-Generation RNA Sequencing, and real-time polymerase chain reaction (qPCR) were used in our proposed study.

Results:
Our data show that ATP5F1E (ATP Synthase F1 Subunit Epsilon), and cAMP regulator, Phosphodiesterase 8B are significantly (P<0.01) preserved in the normal cardiac myofibroblast and aortic endothelial cell. In addition, gene expression of the key ATP synthesis: OPA1, MFN1, TIM, and inflammation marker: MSR1, WNT5 were also significantly (p<0.05) increased in the non-diabetic cardiac myofibroblast and aortic endothelial cell. We next showed that key PPAR pathway regulators, Perilipin 1 (PLIN1) and PPARγ were significantly (p<0.05) increased in our in vitro diabetic cell model. Furthermore, PPARγ inhibitor, FABP4 (fatty acid binding protein-4) which functions as an atherosclerosis promoter was significantly up-regulated in (p<0.05) the non-diabetic cardiac myofibroblast and aortic endothelial cell.

Conclusions:
Mitochondrial ATP production is the main energy source for intracellular metabolic pathways and our study shows that mitochondrial dysfunction and down-regulation of ATP production may inhibit the hydrolysis of the second messenger cAMP that promotes the development of CVD and diabetic cardiomyopathy in CKD.
Abstract 14465: Sex Has an Effect on the Relationship Between Intracoronary Acetylcholine and Coronary Blood Flow
Authors: Ahmad Ali , Toya Takumi , Corban Michel , Ozcan Ilke , Sara Jaskanwal D , Lerman Lilach , Lerman Amir
Published: April 2024

Introduction:
The endothelium controls coronary blood flow (CBF) by regulating microvascular tone, which is an important index of microcirculatory health. The difference in vasomotor response of the microvasculature between males and females is not well described.

Hypothesis:
Males and females react differently to different doses of intracoronary (IC) acetylcholine (Ach) injections.

Methods:
Patients with angina and non-obstructive coronary artery disease (<50% stenosis) that underwent coronary reactivity study were enrolled. A doppler wire was positioned and incremental IC Ach doses were injected (10
-6
, 10
-5
, and 10
-4
mol/L). CBF (mL/min) was then calculated from CAD and doppler-derived flow velocity. Comparisons between the 2 sexes were performed.

Results:
A total of 1927 patients (mean age 51±13 years, 67% females) were included. Males were significantly younger (49±13 vs 53±12, P<0.0001) than females and had a higher smoking exposure rate (56% vs 41%, P<0.0001). Baseline (B) CBF was significantly lower in males (27.7 [19.2; 40.8] vs 30.2 [20.6; 43.4], P=0.04). The gap between females and males widened the first 2 doses, but then diminished after the highest dose (41.2 [24.5; 67.8] vs 44.5 [25.9; 72.0], P=0.09)
(Fig 1A)
. On multivariable analyses, female sex was an independent predictor of higher CBF at all doses (Estimate±StdError) (B= 1.14±0.53; 10
-6
: 1.59±0.61; 10
-5
: 2.54±0.82; 10
-4
: 2.70±1.2; P<0.05 for all). When calculating the %ΔCBF, females had a significantly larger augmentation of flow after the first 2 doses of IC Ach (10
-6
: 3 [-14; 24] vs. -2 [-16; 19], P=0.02; 10
-5
: 21 [-7;68] vs. 12 [-10; 50], P=0.003). However, with the highest Ach dose, there was an equalization of overall augmentation (10
-4
: 49 [-1; 109] vs. 46 [-5; 106], P=0.46)
(Fig 1B).

Conclusions:
Females had higher CBF regardless of given Ach concentration. Females have a higher sensitivity to Ach at smaller doses, while males exhibit a greater vasodilatory reaction at higher doses.
Abstract 6902: Heart Failure Measurements Using Heartlogic Directly Correlates with Increased Burden of Atrial Fibrillation
Authors: Ahmed Rezwan , Thakur Pramodsingh , Biviano Angelo B , Clerkin Kevin , Garan Hasan , Wan Elaine Y
Published: April 2024

Introduction:
Atrial Fibrillation (AF) is a risk factor for death in patients with heart failure (HF). Device sensor measurements from ICDs/CRT-Ds can provide detailed data on the impact of AF on HF. HeartLogic index, HF sensor monitoring can detect worsening HF with high sensitivity.

Hypothesis:
We hypothesize HeartLogic sensors would be able to detect worsening HF with increased AF burden.

Methods:
AF burden was measured as time greater than atrial tachyarrhythmia rate of 170 bpm. Each patient day was grouped into 7 groups based on daily AF burden: No AF/normal sinus rhythm (NSR), >0min, >6min, >1hr, >5.5hr, >12hr, and 24hr. Total 15,533 US patients from ALTITUDE database with HeartLogic devices and a minimum of 365 days of data were analyzed, 754 patients with all 7 levels of AF burden were included. For each group, mean daily heart sounds (S3, S1), respiratory rate (RR), rapid shallow breathing index (RSBI), thoracic impedance (TI), daily and night heart rate (HR, NHR), patient time active, HeartLogic index, and the percent of in-alert days were evaluated. Sensors were compared during each AF burden and during NSR using paired T-test.

Results:
AF burden groups above 6min were associated to significant worsening in S1, RR, RSBI, NHR, HR and HeartLogic index (figure). Significant reduction in patient activity occurred above 5.5hr of AF burden. In-alert days (%) increased significantly during AF burden above 6min compared with NSR.

Conclusions:
This data suggests potential use of HeartLogic sensors to identify patients whose HF status is most impacted by development of AF and those who may benefit most from rhythm control. Additional studies using sensor based AF management may improve clinical outcomes.
Abstract 6913: Measuring Cerebrovascular Reactivity in Moyamoya Disease: Insights from Simultaneous PET/MRI
Authors: Zhao Yize Y , Moseley Michael E , Steinberg Gary , Zaharchuk Greg
Published: April 2024

Introduction:
Cerebrovascular reactivity (CVR) reflects the change in cerebral blood flow (CBF) in response to a vasoactive stimulus. Studies have demonstrated that impaired CVR was associated with a higher risk of stroke. PET imaging with
15
O-water as the radiotracer has been the standard modality to measure CBF and CVR. But it is impractical in most hospitals due to the requirement of an on-site cyclotron. Arterial spin labeling is a quantitative MRI technique that enables non-invasive CBF and CVR measurement.

Hypothesis:
ASL with multiple delays was more accurate than with single delay, using
15
O-water PET as the reference.

Methods:
Data were collected from 26 Moyamoya patients (18-64 years, 16 females) using a simultaneous 3T PET/MRI system (GE SIGNA, Waukesha, WI, USA). All patients had unilateral or bilateral vessel occlusion at the anterior cerebral artery (ACA), middle cerebral artery (MCA), and/or posterior cerebral artery (PCA). Imaging data were acquired using single post-labeling delay pseudo-continuous ASL (single-PLD PCASL), delay pseudo-continuous ASL (multi-PLD PCASL, 3 PLDs), and
15
O-water PET simultaneously at baseline and 15 minutes after the injection of the vasodilator acetazolamide (15 mg/kg with a maximum of 1 g). CBF of PET was computed using the single-compartment pharmacokinetic model; CBF of ASL was computed using the general kinetic model. CVR was computed as the percentage of CBF change compared with baseline CBF. Paired t-tests were performed to compare the mean CVR between the affected and unaffected territories.

Results:
Our quantitative analysis showed that the CVR of the affected regions was significantly lower than the normal regions (by 68%, 52%, and 56% for PET, single-PLD PCASL, and multi-PLD PCASL respectively).

Conclusions:
Both single and multi-delay ASL were effective in detecting impaired CVR in Moyamoya patients.
Abstract 6918: Cardiovascular Magnetic Resonance Imaging Features and Prognostic Value in Immune Checkpoint Inhibitor-Induced Myocarditis
Authors: Cadour Farah , Cautela Jennifer , Rapacchi Stanislas , Varoquax Arthur , Habert Paul , Arnaud Francois , Jacquier Alexis , Meilhac Alexandra , Paganelli Franck , Lalevee Natalie , Scemama Ugo , Thuny Franck
Published: April 2024

Introduction:
Immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M) is an emerging and severe complication of cancer treatment, for which diagnosis and risk stratification are challenging. Very few data exist on CMR findings and predictive value in ICI-M.

Hypothesis:
We hypothesized that ICI-M would have specific CMR features, and we sought to explore the prognostic value of CMR.

Methods:
In this case-control multicenter study, the clinical, biological, and CMR findings (including late gadolinium enhancement [LGE], T1/T2 mapping, and extracellular volume fraction [ECV] values) of adults with ICI-M (n=33) were compared with those of two other groups, including cancer patients without myocarditis scheduled to receive ICIs (w/o-M, n=21), and patients with non-ICI-induced myocarditis (NI-M, n=85). As secondary objective, we explored the potential value of LGE and T1/T2/ECV for predicting major adverse cardiovascular events (MACE) in ICI-M patients.

Results:
Compared with w/o-M, the global native T1, ECV, and T2 z-scores were significantly higher in ICI-M (
P
<0.001 for T1,
P
=0.03 for ECV, and
P
=0.004 for T2). LGE was more frequently observed in ICI-M than in w/o-M (82%
vs.
9%,
P
<0.001). The sensitivity of the main 2018-Lake Louise criteria was only 61% and the specificity was 100% in the diagnosis of ICI-M. No significant difference was found between ICI-M and NI-M in terms of the global native T1, ECV, and T2 z-scores. LGE was less frequent in ICI-M (82%
vs.
100%,
P
<0.001) but was more likely to involve the midwall layer (
P
<0.001) and septal segments (
P
<0.001) than in NI-M. For ICI-M patients, septal LGE was the only CMR predictor of MACE even after adjustment for age, sex, risk factors, left ventricular ejection fraction<50%, and magnitude of increase in peak troponin I or T (adjusted hazard ratio, 3.57; 95% CI, 1.26-10.18;
P
=0.02).

Conclusions:
ICI-M demonstrates specific features on CMR, and septal LGE may be a predictor of poor prognosis.