bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10271: Poor Response and Nonresponse to Clinically Available Supervised Exercise Therapy for Peripheral Artery Disease: A Pooled Analysis
Authors: Whipple Mary O , Salisbury Dereck , Brown Rebecca J , Treat-Jacobson Diane J
Published: June 2023

Introduction:
Nonresponse to supervised exercise therapy (SET) for symptomatic peripheral artery disease (PAD) is a known, but poorly understood, phenomenon affecting approximately one third of individuals. This study evaluated the prevalence and characteristics of poor response and nonresponse among patients with PAD participating in clinically-available SET programs.

Methods:
Data were pooled from four studies (conducted from 2015-2021) embedded within clinically-available SET programs in the Midwest. SET was 12 weeks in duration and included individualized treadmill walking or other exercise modalities (e.g., total body recumbent stepping, cycling) to moderate ischemia, according to patient ability. In addition to providing demographic and medical information, patients completed the 6-minute walk test (6MWT), Short Physical Performance Battery (SPPB), Walking Impairment Questionnaire (WIQ), and PAD Quality of Life Questionnaire (PADQOL) at baseline and 12 weeks. In post-hoc analyses, we examined the prevalence of nonresponse (including no change [≤0 m] or lack of a clinically meaningful change [≤9 m]) in the 6MWT total distance (primary outcome) and other objective and patient-reported outcomes.

Results:
A total of 130 patients (85%) completed SET. Mean (SD) age was 72.3 (8.4), BMI 30.2 (6.3), ABI 0.68 (0.23) and 53.1% of patients were male. Despite the overall improvement observed in 6MWT total distance (34.1 [57.1] meters), there was substantial inter-individual variability in changes in 6MWT total distance over 12 weeks, ranging from a 249.9-meter increase to a 104.6-meter decrease. The prevalence of nonresponse (no change/decline in performance) in 6MWT total distance was 24.6%. The prevalence of poor response (lack of a clinically meaningful improvement) was 32.3%. Similar patterns of poor and nonresponse were observed in both objective and patient-reported measures of physical function.

Conclusions:
The prevalence of nonresponse observed in these clinically available programs is similar to what has been reported in randomized controlled trials. Additional research should examine modifiable predictors of poor and nonresponse to inform programming and maximize an individual’s potential benefit from exercise therapy.
Abstract 10288: Lipoprotein(a) and Long-Term Risk of Atherosclerotic Cardiovascular Disease in a US Pooled Cohort
Authors: Wong Nathan D , FAN WENJUN , Hu Xingdi , Ballantyne Christie M , Hoogeveen Ron C , Tsai Michael Y , Cristino Joaquim , Budoff Matthew
Published: June 2023

Background:
Lipoprotein(a) [Lp(a)] is a common genetic factor associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large prospective primary prevention cohorts of the US population, including those with diabetes.

Methods:
We examined the relation of Lp(a) with ASCVD outcomes in a pooled cohort of five major US prospective studies: the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, Jackson, Framingham Offspring, and Atherosclerosis Risk in Communities. Lp(a) levels were examined continuously (per 50 mg/dL) and categorically as follows: <15 mg/dL (reference), 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, and
>
70 mg/dL. Cox regression, adjusted for age, sex, race/ethnicity, LDL-C, and other risk factors, examined the relation of Lp(a) levels with total incident ASCVD events (non-fatal and fatal myocardial infarction, stroke, revascularization, and coronary heart disease death) in the pooled cohort overall and among those at low-intermediate (<20%) and high (
>
20%) 10-year risk and in those with diabetes.

Results:
We included 27,756 persons without prior ASCVD (mean age 51.3
+
12.4 years, 55.0% female, and 35.7% black participants) who had a mean follow-up of 21.1
+
9.9 years for ASCVD events. The table below shows the adjusted hazard ratios (HRs) and 95% confidence intervals for Lp(a) levels in relation to ASCVD events. In the overall sample, a 50 mg/dL increment in Lp(a) was associated with a 26% greater risk and compared to <15 mg/dL those with Lp(a) levels of 15-29 mg/dL, 30-40 mg/dL, 50-69 mg/dL, and
>
70 mg/dL had 10%, 31%, 44%, and 30% greater risks of ASCVD events. Relationships were stronger in those with diabetes.

Conclusions:
Our results demonstrate in a large pooled cohort of US prospective studies relationships of increased ASCVD risk begin above Lp(a) levels of 15 mg/dL, especially in those with diabetes.
Abstract 10308: Advanced Age Without Percutaneous Coronary Intervention is Associated With Adverse Outcomes in Patients Admitted With St-Segment Elevation Myocardial Infarction: Nationwide Inpatient Sample Analysis
Authors: Fadah Kahtan , Mukherjee Debabrata
Published: June 2023

Introduction:
Coronary artery disease (CAD) in older adults ≥80 years of age is very common and a major cause of morbidity and mortality. Invasive management such as percutaneous coronary intervention (PCI) is sometimes held based on the prediction of poor prognosis, functionality, or advanced comorbidity.

Methods:
Here, we examined the Nationwide Inpatient Sample (NIS) data for baseline characteristics and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) for elderly patients with and without PCI.

Results:
Out of 416195 patients over the age ≥80 of years with primary diagnosis of STEMI, only 39220 (42.3%) underwent PCI. Half of those patients were female (50.7% versus 49.3 %, p<0.001). Patients with baseline characteristics of congestive heart failure (CHF), and renal failure (RF), metastatic cancer disease were less likely to undergo PCI (44.1 % versus 34.2%, 32.7% versus 26.1%, 11.53% versus 9.12%, p< 0.001) respectively. Inpatient hospital mortality for STEMI group without PCI intervention was twice as much compared to those who underwent PCI (45.4% versus 27.6%). Mean length of stay was slightly higher in STEMI patients without PCI (4.44 versus 4.38, p<.0001), while total hospital charges were higher in the PCI group ($114830 ±98516 versus $86131 ±110993, p <.0001). Moderate to severe disability was associated with less PCI intervention (35.5% versus 22.1%, p< 0.001). Furthermore, based on All Patient Refined DRGs (APR-DRG) severity scale, patients with severe loss of function were less likely to be selected for PCI 32.4% versus25.6%, p< 0.001)

Conclusions:
Advanced age was associated with poorer hospital outcomes in STEMI patients without PCI. Disability severity and APRDRG severity scale were associated with decision not to perform PCI. Older patients with baseline comorbidities of CHF, RF, and metastatic disease were also less likely to undergo PCI after STEMI.
Abstract 10315: The Effect of Protease-Activated Receptor-1 Inhibition With Vorapaxar in Post-mi and Nstemi Patients on Selected Biomarkers Reflecting Endothelial Function
Authors: Nilsen Dennis W , Røysland Michelle , Ueland Thor , Aukrust Pal , Michelsen Annika E , Staines Harry , Barvik Ståle , Kontny Frederic , Nordrehaug Jan Erik , Bonarjee Vernon V
Published: June 2023

Introduction:
Biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has essentially focused on platelets. Follow-up (FU) time has been short, whereas in the current study, focus has been on endothelial function during both short- and long-term PAR-1 inhibition.

Aim:
To assess short- and long-term effects of vorapaxar (V) as compared to Placebo (PL) on the following biomarkers: Angiopoietin-2 (ANGPT2), Angiopoietin-like 4 (ANGPTL4), VEGF, ICAM-1, VCAM-1, E-Selectin (ESEL), von Willebrand Factor (VWF), Thrombomodulin (TM), PAI-1 and PAI-2.

Methods:
In an independent collective subproject performed in Norway, post-MI patients at steady state were recruited from the “Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients with Atherosclerosis” (TRA2ᵒP-TIMI 50) and NSTEMI patients were recruited from the “Thrombin Receptor Antagonist for Clinical Event Reduction in acute coronary syndrome” (TRACER) trial. Biomarkers were measured in duplicate by enzyme immunoassays (EIA) in citrated plasma at one month follow-up and at study completion (median 2.3 years) for subjects recruited from both trials.

Results:
Biomarkers were measured in 265 consecutive patients [age median 62.0 years (Q1-Q3: 55.0-68.0 years), males 83%] with at least one change from baseline value. Among these, biomarkers were available at both short- and long-term follow-up in 221 subjects.

ANGPT2 increased significantly in V as compared to PL at 1-month follow-up in the total population (p=0.034), and in males in both post-MI (p=0.031) and NSTEMI subjects (p=0.012), respectively. ANGPTL4 increased (p=0.028) and PAI-2 decreased (p=0.025) significantly in the total population in favor of V at final FU. In the total post-MI subgroup and among males of that group, a short-term significant increase in ESEL in favor of V was observed, p=0.029 and p=0.018, respectively. Also, a transient significant increase in VWF (p=0.032) in favor of V was seen at one month in NSTEMI patients.

Conclusions:
Significant changes suggesting potential harmful effects in some biomarkers were observed during 1-month and long-term PAR-1 inhibition as compared to placebo in post-MI and acute coronary syndrome patients.
Abstract 10325: Feasibility and Predictive Utility of Three-Dimensional Myocardial Deformation Analysis From Multi-Phase Computed Tomography Angiography in Transcatheter Aortic Valve Replacement
Authors: Rabbani Mohamad , Satriano Alessandro , Lydell Carmen , Bristow Mike , Fatehi Hassanabad Ali , Mustafa Alhussein Muhammad M , Liang Zhiying , Tao Eric , Bizios Anna , Adams Corey , Fine Nowell , Howarth Andrew G , Kent William , Chu Michael W , White James
Published: June 2023

Introduction
: Multi-phase computed tomography angiography (CTA) for the pre-procedural planning of TAVR presents a unique opportunity to assess 3D myocardial biomechanics. Using a novel approach, we assessed the feasibility and predictive utility of 3D myocardial deformation analysis (3D-MDA) to deliver principal strain (PS) based markers of left ventricular (LV) health for the prediction of time to heart failure hospitalization or death following TAVR.

Methods:
205 patients undergoing a pre-TAVR CTA and followed clinically for >6 months were identified. Whole-heart segmentation with 3D-mesh modelling was followed by 3D-MDA of the LV. 3D global LV minimum PS (minPS) was calculated for endocardial, epicardial and transmural layers. Cox regression models were performed to evaluate associations between 3D minPS and the composite outcome of all-cause mortality or heart failure hospitalization.

Results:
Of 205 patients, 196 (96%) had analyzable CTA data for 3D-MDA. Median (IQR) age was 85 (79.5-88) years (55% male) with median STS-PROM score 3.10 (2.10-4.55)% and median echocardiography LVEF 60 (55.9-65.0)%. Over 25 (11-36) months 55 patients (28%) experienced all-cause death or HF hospitalization. Patients with lower 3D minPS, below -23.7%, experienced a 3-fold increased risk of the primary outcome (p<0.001). Following adjustment for baseline characteristics, inclusive of STS and LVEF, 3D minPS remained independently associated with the primary outcome: endocardial 3D minPS providing highest prognostic value [HR (95% CI) of 1.09 per 1% change (1.04-1.15), p<0.001].

Conclusions:
3D-MDA of pre-TAVR multi-phase CTA is feasible and delivers principal-strain based markers strongly predictive of future clinical outcomes. The potential of this approach to optimize patient selection and post-procedural management requires future evaluation in a multi-centre setting.
Abstract 10330: Do Radiofrequency and Cryoballoon Pulmonary Vein Isolation Induce Similar Rates of Pericardial Inflammation?
Authors: Schanz John , Wang Jonathan , Frisch Daniel R , Pavri Behzad B
Published: June 2023

Introduction:
Pericardial inflammation/irritation (P
I/I
) is a known occurrence after Radiofrequency (RF) and Cryoballoon (CB) pulmonary vein isolation (PVI) for pts with AF. We hypothesized that any new pericardial effusions (PE) or ECG evidence of pericarditis were clinical manifestations of P
I/I
post-PVI. Data comparing the incidence and clinical significance of P
I/I
between the 2 treatment modalities are limited.

Methods:
Retrospective analysis of post-PVI P
I/I
in pts undergoing either CB or RF ablation for AF. We included
any
degree of new PE or ECG changes consistent with pericarditis seen post-procedure as a surrogate for P
I/I
.

Results:
A total of 224 pts (70 CB and 154 RF) with AF undergoing their first PVI were studied. Compared to RF, CB pts tended to be female (47.1% vs 31.2%, P=0.021), were less likely to receive concurrent cavotricuspid-isthmus (CTI) ablation (4.29% vs 61.0%, P<0.01), and were less likely to receive post-PVI NSAIDs (17.1% vs 56.5%, P<0.01). Despite differences in baseline characteristics, the incidence of post-PVI P
I/I
between CB and RF was similar (17.1% vs 20.8%, P=0.469). No episode of P
I/I
led to any hemodynamic instability or required intervention. Pts with P
I/I
were more likely to be female (52.3% vs 32.4%, P=0.014) and had lower BMIs (28.7kg/m
2
vs 31.2kg/m
2
, P=0.012). Characteristics of pts in each treatment group as well as pts with and without P
I/I
were summarized in Table 1.

Conclusions:
In contrast with prior studies that demonstrated lower rates of P
I/I
with CB, we demonstrate similar rates of P
I/I
with CB and RF. The occurrence of P
I/I
was not associated with increased incidence of early AF recurrence. P
I/I
was more likely to develop in female pts with lower BMI. Although NSAIDs are often used post-PVI, we found no association between NSAID use and development of P
I/I
.
Abstract 10335: Implementation of a Population Health Infrastructure for Hypertension in a Primary Care Clinic Setting
Authors: Yabut Jevin , Becker Erica , Lico Ina , Muco Erind , Vergara Cunegundo
Published: June 2023

Introduction:
In 2021, 48% of patients in the Hartford Hospital Adult Primary Care (APC) Clinic with a diagnosis of hypertension had controlled blood pressures of <140/90 compared to 63% in Hartford Healthcare (HHC) as a whole. This demonstrates potential healthcare disparities within the APC clinic, whose patient panel consists primarily of an underserved Hispanic population with Medicare, Medicaid or are uninsured and lack overall health literacy. The aim of this project is to have 75% of APC patients with hypertension to have blood pressures of <140/90 by 2023.

Methods:
The team implemented standardized staff and resident training regarding blood pressure measurement and ACC/AHA Hypertension Guidelines with pre- and post- training surveys. Residents reviewed their patient roster to schedule appointments for those with uncontrolled hypertension. The team created an Epic SmartPhrase to incorporate standard work by all providers for initial and follow-up hypertension visits. This included blood pressure-lowering medications, environmental risk factors, evaluation for obstructive sleep apnea, and recommendations for nonpharmacological interventions. Staff implemented standardized workflow which included: repeat blood pressure measurement after 5 minutes of rest for blood pressures >140/90, ensuring proper documentation of repeat blood pressure in correct field in Epic, and scheduling 3-week follow-up appointments for blood pressure management. The clinic has been approved for a grant for BP monitors for those without health insurance.

Results:
In May 2022, 52% (727/1409) of patients at APC had blood pressures of <140/90 compared to 38% (104453/272615) at HHC.

Conclusion:
Implementation of standardized staff and resident training, Epic SmartPhrases, and clinic workflow may lead to improved blood pressure control in an academic primary care clinic. Future direction includes assessing if optimizing BP control leads to improved patient outcomes.
Abstract 10337: Early Adaptation of the Mitral Valve After St-Elevation Myocardial Infarction
Authors: Senechal Dumais Isabelle , Deschenes Valerie , Marsit Ons , Hadjadj Sandra , Clavel Marie-Annick , Pibarot Philippe , Bucknell Rebecca , Vallerand Andreanne , Handschumacher Mark , Levine Robert , Beaudoin Jonathan
Published: June 2023

Introduction:
Ischemic mitral regurgitation (IMR) is associated with worse outcomes and higher mortality after myocardial infarction (MI). Clinical observations and experimental data have shown that mitral valve leaflets have the potential to enlarge over time to compensate left ventricular remodeling and prevent IMR. Previous animal studies have demonstrated that MI is associated with fibrotic changes in the mitral valve leaflets and prevent this adaptive compensation. However, the timing of mitral valve geometric changes are not well described. While previous data shows an increase in leaflet size at 6 and 12 months after MI, its short-term evolution after an ischemic event is not well documented.

Methods:
Twenty-two patients with ST-elevation myocardial infarction and initial left ventricular ejection fraction ≤ 45% were enrolled in Quebec Heart and Lung Institute. Participants had 3D transthoracic echocardiography (TTE) at baseline and 3 months, as well as cardiac magnetic resonance (CMR) at 3-month follow-up. Mitral valve leaflet size was measured from the 3D TTE using a custom software (Omni4D). CMR was used to derive left ventricular volumes, function and mitral regurgitant volume. Significant IMR was defined as a mitral regurgitant fraction ≥ 15% derived from the 3-month CMR.

Results:
Twenty-one of the 22 patients completed the imaging follow-up. Left ventricular ejection fraction at 3 months was 53 ± 10% (range from 37 to 69%). Eight patients (38%) had mild IMR at 3 months. Mitral valve surface area was significantly increased at 3 months compared with baseline for patients without IMR (10.96 ± 1.78 cm
2
vs 9.51 ± 1.62 cm
2
; p = 0.001). Valve enlargement vs baseline was significantly greater in patients without IMR (+17 ± 13% vs -5 ± 4% for those with IMR at follow-up, p=0.0007).

Conclusions:
Mitral valvular surface increases within the first few months after MI, but not in all patients. Adequate valve enlargement seems related to the absence of IMR at 3 months.
Abstract 10353: Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3 Year Results of the SUCCOUR Trial
Authors: Negishi Tomoko , Thavendiranathan Paaladinesh , Negishi Kazuaki , Penicka Martin , Lemieux Julie , Murbraech Klaus , Miyazaki Sakiko , Shirazi Mitra , Santoro Ciro , Cho Goo-Yeong , Popescu Bogdan A , Kosmala Wojciech , Costello Ben , La Gerche Andre , Mottram Philip , Thomas Liza , Seldrum Stephanie , Hristova Krasimira , Bansal Manish , Kurosawa Koji , Fukuda Nobuaki , Yamada Hirotsugu , Izumo Masaki , Tajiri Kazuko , Sinski Maciej , Vinereanu Dragos , Shkolnik Evgeny , Banchs Jose , Kutty Shelby ,   SUCCOUR investigators, Marwick Thomas
Published: June 2023

Introduction:
Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction (CTRCD) and guide initiation of cardioprotection (CPT) at the time of chemotherapy. No prospective randomized controlled trial (RCT) has identified the impact on LV function in survivors.

Hypothesis:
GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care.

Methods:
In this international (28 sites) multicenter prospective RCT, patients (pts) were included if they were administrated anthracyclines and had another risk factor for HF. They were randomly allocated into undergoing GLS-guided CPT for >12% relative reduction in GLS or EF-guided CPT for >10% absolute reduction of EF. Primary endpoint was the change in EF (ΔEF) from baseline to 3 years by 3D echocardiography.

Results:
Among 331 pts enrolled, 255 (77%, 60±16 years, 95% women) completed 3-year follow-up (123 in EF-guided group and 132 in GLS-guided). Most had breast cancer (236, 93%), 67 (26%) with hypertension and 32 (13%) with diabetes mellitus. A regimen of anthracycline and trastuzumab was the most common chemotherapy regimen (84%). The baseline LVEF was 61±4% with GLS of 20.7±2.3% in the entire population. CPT was administrated in 18 pts (15%) in EF-guided and 41 (31%) in GLS-guided (p=0.02). Most patients showed recovery in EF and GLS after chemotherapy (Figure). ΔEF was -2.0±4.8 in EF-guided and -1.4±5.4 in GLS-guided (p=0.25), but LVEF at 3 years in EF-guided was lower than that of GLS-guided (58.0±5.6% vs 59±4.9%, p=0.043). Ten pts in EF-guided developed CTRCD, and 6 in GLS-guided (p=0.24).

Conclusions:
Most of the enrolled pts were taking potentially cardiotoxic chemotherapy for breast cancer. Almost all improved LV function over 3 years, and although GLS-guided CPT was associated with higher EF at 3 years, there was no difference in ΔEF compared with EF-guided surveillance.
Abstract 10369: Meta-Analysis of Coronary Computed Tomography versus Invasive Coronary Angiography in Stable Chest Pain
Authors: Al-Abdouh Ahmad , As-Sayaideh Mohammad , Mhanna Mohammed , Abusnina Waiel , Jabri Ahmad , Barbarawi mahmoud , Alabduh Taqwa , Talib Usama , Upadhrasta Sireesha , Paul Timir K
Published: June 2023

Background:
The coronary computed tomography angiography (CCTA) is a noninvasive alternative tool in diagnosis of coronary artery disease compared to invasive coronary angiography (ICA). However, there is uncertainty regarding its usefulness in reducing major adverse cardiovascular events in stable chest pain patients.

Methods:
We have searched EMBASE, PubMed, and Cochrane Library (inception through May 24
th
, 2022) for randomized controlled trials (RCTs) evaluating CCTA versus ICA in stable chest pain. The Mantel-Haenszel method was used with Paule-Mandel estimator of tau
2
and Hartung-Knapp-Sidik-Jonkman adjustment (given small number of the included studies) to calculate the risk ratio (RR) and 95% confidence interval (CI).

Results:
Three RCTs with a total of 5,393 patients were included in this study. There was no significant difference between CCTA and ICA in terms of myocardial infarction [RR: 1.12; 95%CI: 0.60; 2.09; I
2
:0%]
[Figure
], stroke [RR: 0.52; 95%CI: 0.22; 1.24; I
2
:0%], all-cause mortality [RR: 1.83; 95%CI: 0.17; 20.18; I
2
:50%], or cardiovascular mortality [RR: 0.47; 95%CI: 0.02; 9.15; I
2
:0%].

Conclusion:
This meta-analysis suggests that there is no difference between CCTA and ICA for stable chest pain evaluation in terms of myocardial infarction, stroke, all-cause mortality, or cardiovascular mortality.
Abstract 10389: Interleukin-1 Blockade With Anakinra Restores Cardiac Contractility Reserve and Exercise Capacity in a Mouse Model of Ischemic Heart Failure
Authors: Narayan Pratyush , Vohra Habeebah , MEZZAROMA Eleonora , Kim Michelle , Van Tassel Benjamin , Abbate Antonio , Toldo Stefano
Published: June 2023

Background:
Acute myocardial infarction (AMI) is associated with an intense inflammatory response promoting adverse cardiac remodeling, impaired cardiac reserve, and reduced exercise capacity, hallmarks of heart failure. Interleukin-1β (IL-1β) is the prototypical inflammatory cytokine that is increased in AMI and is sufficient to impair cardiac reserve when administered exogenously in mice. Whether blocking IL-1β signaling with recombinant IL-1 receptor antagonist, anakinra, can restore cardiac contractile reserve and improve exercise capacity in AMI is unknown.

Methods:
We induced ischemic heart failure due to large non-reperfused anterior AMI in mice via surgical permanent ligation of the left anterior descending artery via lateral thoracotomy in 10-week-old male CD1 mice (N=30, 32-37 g in weight) followed for 10 weeks. Anakinra was given as intraperitoneal injection of 10 mg/kg, 0.2 ml, for three consecutive days. Cardiac contractile reserve was measured assessing changes in left ventricular fractional shortening with isoproterenol challenges (N=5). A subgroup of mice that had been previously trained to run on treadmill were used to measure interval changes in exercise capacity 10 weeks after AMI and with three consecutive days of anakinra treatment (N=6). Data are presented as mean and standard error of mean. T-test for paired group analysis was used to compare values.

Results:
Cardiac contractile reserve was impaired at -10±5% and restored with anakinra given for three days to +49±11% (p=0.008). Exercise capacity was also significantly reduced with AMI at 191±39 m and restored to 247±46 m after anakinra treatment (p=0.03).

Conclusion:
Ischemic heart failure due to large non-reperfused AMI leads to a severe reduction in cardiac contractility reserve and exercise capacity that are reversed by IL-1 blockade with anakinra.
Abstract 10397: Unbiased Cluster Modelling for Uncovering Natural Distribution of Doppler Derived Diastolic Variable Response to Exercise Among Patients Referred to Exercise Echocardiography
Authors: Omar Alaa M , Konje Swiri , Alam Loba , Gandhi Kruti , Moras Errol , Mancero Brissete , Zipf Elizabeth , Meister David , Pena Maria , Perez Lizardo Christopher , Kim, Ga Hee Ga Hee , Elias Joseph , Argulian Edgar
Published: June 2023

Introduction:
Exercise-induced diastolic dysfunction is associated with poor prognosis.

Hypothesis:
We studied diastolic response to exercise based on the natural distribution of Doppler variables and its relationship to adverse outcomes.

Methods:
In a retrospective study, 813 patients referred for exercise echocardiography (ExE) for ischemia assessment were included (Age: 58±13 years, 57% females, EF:60±7%). A 2-step unsupervised cluster model was constructed using resting and post-exercise tissue Doppler early diastolic mitral annular velocity, post-exercise pulsed Doppler-derived mitral inflow velocity in early and late diastole, and post-exercise tricuspid regurgitation velocity. Clusters were compared for a composite outcome (death, cardiac rehospitalization, acute coronary syndrome, and need for future ischemia testing).

Results:
Exercise-induced ischemia occurred in 116(14%). The composite outcome occurred in 196(24%) patients over a median follow-up of 3.2 years. The model yielded 2 clusters labelled low and high risk for the composite outcome, Figure 1 A,B). Compared to the low risk cluster, patients in the high risk cluster were older, had more risk factors and comorbidities, worse exercise performance, worse resting and exercise diastolic variables, and more ischemic ExE. After stratification for ischemia, clusters resulted in significant separation of risk for the outcome, regardless of the presence or absence of ischemia (Figure 1 C,D). These findings persisted after multivariate adjustment.

Conclusions:
In patients referred to ExE for assessment of ischemia, diastolic response to exercise involves complex interactions among diastolic variables. Appreciation of such complexity seems to add prognostic value beyond ischemia, suggesting a need for novel approaches for characterization of the natural distribution of diastolic variables, such as computational unbiased clustering.
Abstract 10427: Association Between Blood Pressure Levels and Prevalence of Premature Atrial Contractions in Patients With Hypertension
Authors: Mostafa Mohamed A , Soliman Mai , li yabing , Singleton Matthew J , Soliman Elsayed Z , Ahmad Muhammad
Published: June 2023

Background:
High blood pressure (BP) leads to left atrial functional and structural abnormalities, which is the substrate for atrial arrhythmias. We hypothesized that, among patients with hypertension, higher levels of systolic BP (SBP) would be associated with a higher prevalence of premature atrial contractions (PACs), the most common cardiac arrhythmia that has been associated with poor outcomes in the general populations.

Methods:
This analysis included 4,497 (mean age 62.1±13.2 years, 49.9% women, 48.9% Whites) participants with hypertension from the Third National Health and Nutrition Examination Survey who were free of clinical cardiovascular disease (CVD). Multivariable logistic regression analysis was used to examine the cross-sectional association between SBP and the prevalence of PACs ascertained from electrocardiograms (ECGs) read at a central ECG core. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality occurring during follow-up.

Results:
About 1.6% (n=74) of the participants had PACs at baseline. Patients with SBP <140/<90 mmHg had lower prevalence of PACs compared to those with SBP
>
140/≥90 mmHg (1.12% vs. 1.99%, p-value=0.019). Each 10 mmHg lower in SBP was associated with 11% lower odds of PACs in a multivariable logistic regression model adjusted for demographics, CVD risk factors, and major ECG abnormalities (OR (95%CI): 0.89 (0.78-1.02)). A total of 645 CVD deaths occurred during 14 years of follow-up. Presence (vs. absence) of PACs was associated with a 70% increased risk of CVD mortality in Cox models adjusted for demographics, CVD risk factors, and major ECG abnormalities (HR (95%CI): 1.70 (1.14-2.52)).

Conclusions:
Among patients with hypertension, presence of PACs is associated with an increased risk of CVD mortality, and lower levels of BP are associated with a lower prevalence of PACs. These findings highlight the potential role of intensive BP lowering in managing cardiac arrhythmias in hypertension patients.
Abstract 10428: Probability of Atrial Fibrillation (AF) Diagnosis and Error in Estimation of Burden in People With Paroxysmal AF Based on the Duration of Monitoring
Authors: Lee Victoria H , Steinhubl Steve , Quer Giorgio
Published: June 2023

Introduction:
In individuals with paroxysmal atrial fibrillation (PAF) undergoing heart rhythm monitoring, total duration of monitoring can influence both the probability of recognizing AF and estimation of burden. We estimate the probability of AF detection and quantify the error in burden estimation based on the duration of monitoring up to 10 days.

Methods:
Data included 5361 ECG patch recordings up to 14 days long with at least 1 episode of AF. 100 samples of pre-specified lengths were drawn at random from each recording. For each sample length, the probability of identifying any AF, and the AF burden over shorter periods of monitoring were determined. The absolute error in burden estimation over short monitoring divided by the true AF burden during up to 14 days of monitoring was used to determine relative deviation. We stratified the expected relative deviation and probability of detecting AF by high (>10%), moderate (2-10%), or low (<2%) true AF burden.

Results:
Estimated probability of detecting any AF was significantly affected by duration of monitoring (Fig): 1 day of monitoring identified 76% [75-77%], 52% [51-54%] and 35% [33-36%] of individuals with high, moderate, and low burden of AF. Relative deviation in the estimation of AF burden is also significantly impacted by monitoring duration with 1 day recording, with 0.89 [0.87-0.91], 1.45 [1.43-1.47], and 1.65 [1.63-1.67] for high, moderate, and low burden. Even for 7 days recording, the expected deviation is significant, with 0.31 [0.30-0.33], 0.60 [0.58-0.61], 0.79 [0.78-0.80] for high, moderate, and low burden (Fig).

Conclusions:
In people with PAF, known or unknown, the duration of continuous ECG recording can significantly impact both ability to diagnosis AF and accurate determination of AF burden. Even in individuals with true AF burden >10%, 24 hours of monitoring will not detect AF in >20% of people and provide an almost 90% relative error in the estimate of AF burden.
Abstract 10463: Neighborhood Social Vulnerability and Interstage Weight Gain: Evaluating the Role of a Home Monitoring Program
Authors: Shustak Rachel J , HUANG JING , Tam Vicky , stagg alyson , Giglia Therese M , Ravishankar Chitra , Mercer-Rosa Laura , Guevara James P , Gardner Monique M
Published: June 2023

Introduction:
Interstage (IS) growth failure is a risk factor for poor outcomes in infants with hypoplastic left heart syndrome (HLHS). We hypothesize that children with greater social vulnerability are at greater risk for IS growth failure. However, IS home monitoring may mitigate disparities in IS weight gain. We sought to examine the impact of an Infant Single Ventricle Management and Monitoring Program (ISVMP) on the association of neighborhood social vulnerability and IS weight gain.

Methods:
We performed a retrospective single-center cohort study of infants with HLHS before (2007-2010) and after (2011-2020) the introduction of the ISVMP. IS weight gain was measured in grams per day (gm/day) and growth failure was defined as an average IS weight gain of <20 gm/day. Neighborhood social vulnerability was measured by the Centers for Disease Control Social Vulnerability Index (SVI) with higher SVI values representing greater vulnerability. Linear and logistic regression models were used to examine the association between SVI and IS weight gain and growth failure. Models were adjusted for demographic, operative, and discharge characteristics. To test for effect modification by ISVMP, we introduced an interaction term into the models and calculated pre- and post- stratum-specific effect estimates.

Results:
In total, 328 infants with HLHS, were evaluated 111 before and 217 after the introduction of the ISVMP. In the total cohort, SVI was significantly associated with IS growth failure (P= 0.001). Enrollment in ISVMP strongly attenuated the association of SVI and IS growth failure (P = 0.04). Prior to ISVMP, infants in the highest and middle SVI tertiles gained 4 gm/day less than infants in the lowest SVI tertile and were more likely to experience IS growth failure (high vs. low: aOR 12.5; 95% CI 2.5-62.2; middle vs. low: aOR 7.8; 95% CI 2.0-31.2). However, after the introduction of the ISVMP, there was no difference in IS weight gain or growth failure by SVI tertile. Middle and high SVI infants enrolled in ISVMP gained 4 gm/day and 2 gm/day more than their pre-ISVMP counterparts, respectively.

Conclusion:
High social vulnerability is a risk factor for poor IS weight gain in infants with HLHS. However, enrollment in ISVMP significantly reduces growth disparities.
Abstract 10465: Abnormal Post Exercise Skeletal Muscle Microvascular Response and Metabolism Correlate With Patient Reported Outcomes in Patients With Intermittent Claudication From Peripheral Artery Disease
Authors: Divakaran Sanjay , Harms Hans , Robertson Matthew , Merugumala Sai , Park Mi-Ae , Kijewski Marie , Martell Laurel , Morgan Victoria , Barrett Leanne , Perillo Anna , Bibbo Courtney , Yang David , Jarolim Petr , Feinberg Mark W , Lin Alexander , Bonaca Marc P , DI CARLI MARCELO
Published: June 2023

Background and Aims:
Intermittent claudication (IC) in patients with peripheral artery disease (PAD) is thought to be caused by reduced lower extremity macrovascular blood flow. However, the ankle-brachial index (ABI) (a macrovascular measure) does not correlate well with patient-reported outcome measures. We aimed to study microvascular and metabolic skeletal muscle responses to exercise in patients with IC using positron emission tomography (PET).

Methods:
We enrolled 19 patients with IC (ABI < 0.90 and imaging/angiographic evidence of PAD) and 12 healthy controls (HCs) (normal ABI). All subjects underwent rest perfusion imaging of the legs with
13
N-ammonia or
11
C-acetate PET followed by a graded treadmill test. Subjects exercised until limited by claudication or the end of the 20-minute protocol. Subjects then underwent immediately post-exercise PET imaging of the legs. Skeletal muscle blood flow (SMBF) was quantified in each leg at rest and immediately post-exercise. Skeletal muscle oxygen utilization (SMVO
2
) normalized to SMBF was also quantified for patients who underwent imaging with
11
C-acetate. Peripheral artery questionnaire (PAQ) summary score was obtained for all subjects.

Results:
We found that SMBF was increased post-exercise in all subjects, and stress/rest SMBF was higher in the legs of subjects with PAD than in the legs of HCs (
Figure 1A
). We also found that stress SMVO
2
/SMBF was higher in legs of patients with PAD than in the legs of HCs (
Figure 1B
). There was a moderate, significant correlation between limb stress/rest SMBF and PAQ score (
Figure 1C
) and a strong, significant correlation between limb stress SMVO
2
/SMBF and PAQ score (
Figure 1D
).

Conclusions:
In conclusion, we found that SMBF increased in all subjects after treadmill exercise and paradoxically to the greatest degree in patients with IC. We also found that PET-derived markers of post-exercise microvascular perfusion and metabolism correlated with patient-reported outcomes.
Abstract 10475: Serial Inflammatory Cytokine Levels Are Increased in Atrial Fibrillation After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy
Authors: Lee Dae H , Jain Michael , Faramand Rawan G , Reid Kayla , Lee Sae Bom , Corallo Salvatore , Hidalgo-Vargas Melanie , Kumar Abhishek , Chandrasekhar Sanjay , Chavez Julio , Shah Bijal , Lazaryan Aleksandr , Khimani Farhad , Nishihori Taiga , Bachmeier Christina , Locke Frederick , Oliveira Guilherme , Alomar Mohammed , Davila Marco L
Published: June 2023

Introduction:
Chimeric Antigen receptor T- Cells (CAR-T) are novel therapy for various malignancies, including lymphoma. Cardiotoxicity such as heart failure, arrhythmia, and acute coronary syndrome frequently occurs in the setting of cytokine release syndrome (CRS).

Hypothesis:
We aimed to investigate the changes in inflammatory cytokines in patients who develop cardiotoxicity after CAR-T therapy.

Methods:
This was a prospective observational cohort study involving patients diagnosed with lymphoma treated with CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel). Serum cytokines interleukin (IL)-2, IL-6, IL-15, IFN-gamma, TNF-alpha, GM-CSF, and angiopoietin 1 & 2 were tested before lymphodepletion and daily during index hospitalization. Cytokines were analyzed using the ELLA Immunoassay system (SimplePlex, Protein Simple) and reported in pg/mL. Cardiac events were adjudicated by a cardio-oncology team.

Results:
Fifty-three patients with a complete set of cytokine levels were analyzed. There were 9 cardiac events after CAR-T (8 atrial fibrillation and 1 cardiomyopathy). Patients with cardiac events were older and had higher baseline creatinine level and left atrial volume. All cardiac events occurred in patients who had low-grade CRS (5 Grade 1 and 4 Grade 2 CRS). Tocilizumab was given to seven patients. Pre-CAR-T baseline inflammatory cytokine levels were not different in the cardiac event group. However, median peak IFN-gamma, IL-6, and IL-15 levels were higher median in the cardiac event group (Figure 1).

Conclusions:
In the setting of CAR-T, the elevation of multiple pro-inflammatory pathways from cytokine release syndrome may be related to the adverse cardiac events, including atrial fibrillation. Further studies are needed to identify and investigate the role of specific inflammatory mediators in cardiac events after CAR-T therapy.
Abstract 10482: High Sensitivity Troponin I and Myocardial Injury After Noncardiac Surgery in Cancer Patients: A Prospective Observational Cohort Study
Authors: Liu Todd J , McCormick Patrick , Fischer Gregory , Tan Kay See , lee jasme , AMAR David , Ramanathan Lakshmi V , Chen Carol , Murtagh Gillian , Blouin Amanda
Published: June 2023

Introduction:
Myocardial injury after noncardiac surgery (MINS) is diagnosed when a postoperative troponin concentration exceeds the 99
th
percentile upper reference limit for a presumed ischemic mechanism and is associated with increased perioperative mortality. Our goal was to investigate the prognostic characteristics of MINS in a wide oncologic surgical population using fourth generation (TnI) and fifth generation high-sensitivity (hsTnI) troponin-I assays.

Methods:
In this prospective cohort of adults who underwent noncardiac cancer surgery, waste blood was collected daily until postoperative day three for TnI and hsTnI. MINS was explored using peak postoperative elevation using three definitions: (1) MINS
TnI
= TnI (≥ 0.06 ng/mL), (2) MINS
hsTnI
= hsTnI (≥ 17 ng/L for females or ≥ 35 ng/L for males), or (3) MINS
either
= either TnI or hsTnI elevation. The association between each MINS definition and the endpoints (30-day mortality, observed to expected length of stay ratio [O:E LoS]) were quantified via logistic and log-linear regression.

Results:
The incidence of MINS
TnI,
MINS
hsTnI
, and MINS
either
were 4.6%, 9.3%, and 9.5% respectively. In univariable analysis, MINS
hsTnI
was associated with an increased risk of 30-day mortality with an odds ratio (OR) of 3.30 (95% confidence interval 1.07, 8.57; p=0.039). Similar results were found for MINS
either
but were not statistically significant for MINS
TnI
. Cardiotoxic chemotherapy had a 3-fold increased odds of 30-day mortality and a higher incidence of MINS
hsTnI
(12%) when compared to non-chemo patients (9%). Change in O:E LoS was statistically significantly higher (25%) in patients with MINS
hsTnI
.

Conclusion:
In a large oncology cohort, MINS was associated with increased odds of 30-day perioperative mortality. HsTnI assays may be better suited to screen for MINS. The relationship of cardiotoxic chemotherapy to MINS risk warrants further investigation.
Abstract 10484: Carotid Plaque Score Adds Discriminatory Benefit to the Stress Echo for Major Adverse Cardiovascular Events in Low-Intermediate Risk Cardiac Patients
Authors: Matangi Murray , Hetu Marie-France , Armstrong David , Jonas Shellenberger , Brouillard Daniel , Bakker Josh , Johnson Ana , Johri Amer M
Published: June 2023

Introduction:
Carotid plaque is recommended for cardiac risk stratification for intermediate risk patients but has not been integrated into cardiology community clinics to help refine testing and reduce risk for major adverse cardiovascular events (MACE). The purpose was to determine the clinical usefulness of carotid plaque score (PS) to guide management of low-intermediate risk patients.

Methods:
Patients 40-75 years who received a carotid ultrasound were followed up to 10 years for MACE (cardiovascular death, myocardial infarction, stroke). Low-intermediate risk participants (n = 9,114) with no known cardiovascular disease were included. Administrative data holdings housed at IC/ES were used for event follow-up. Kaplan-Meier curves and Cox proportional hazard ratios determined relative risk. Combining plaque score (Rotterdam method, plaque presence within carotid segments, PS 0 to 6) with stress echo (SE) was assessed in a subset of participants (n = 624).

Results:
The optimum threshold for PS = 2 for 1-year MACE (AUC = 0.738). The population rate of MACE over 10 years was 4%. In participants referred for SE, PS of <2 was associated with an excellent 5-year outcome irrespective of the SE result (PS<2 = 0.9% MACE, normal SE = 1.6% MACE). A PS of ≥2 and an abnormal SE was associated with increased risk (MACE = 11%). The hazard ratio for MACE increased with PS from 1.08 to 9.86 (PS = 1 and 6; reference PS=0). Combining SE with PS (either test positive) increased the sensitivity of the SE from 36% to 71%, with an excellent specificity (SE alone = 94% vs SE+PS = 87%).

Conclusions:
In low-intermediate risk patients, if a PS is <2, cardiac testing for atherosclerotic risk is not required for up to 5 years. However, patients with a PS of ≥2 should undergo a stress echo. Combining SE with PS adds discriminatory benefit in identifying risk for MACE. This simple stratification parameter can be easily integrated in community cardiology clinics to prioritize patients requiring further testing.
Abstract 10489: CVSA Early Career Investigator Award Finalist: Restrictive or Liberal Transfusion for Acute Coronary Syndromes - Insights From the TRICS-III Randomized Controlled Trial, Systematic Review, and Meta-Analysis
Authors: Mistry Nikhil , Hare Greg , Shehata Nadine , Papa Fabio , Kramer Robert S , SAHA TARIT , Verma Subodh , Mazer David
Published: June 2023

Introduction:
The optimal transfusion strategy for patients with ACS is unclear. Current data are inconclusive and there is a paucity of long term data; therefore, we performed a subgroup analysis of patients with AMI in the Transfusion Thresholds in Cardiac Surgery (TRICS-III) randomized controlled trial (RCT) to add evidence addressing this important clinical question, and interpret the results in the context of a systematic review and meta-analysis.

Methods:
The TRICS-III trial randomized patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate-to-high risk of death to restrictive transfusion (transfuse at hemoglobin <7.5g/dL) or a liberal strategy (operating room and ICU: transfuse at hemoglobin <9.5g/dL; ward: <8.5g/dL). AMI patients were those undergoing coronary artery bypass graft surgery with a recent MI and ≥1 of the following enrichment criteria: unstable angina, critical preoperative state, preoperative intra aortic balloon pump, and/or emergency surgery. The primary outcome for this analysis was MACE (all-cause death, MI, and revascularization) at 6 months.

The MEDLINE and EMBASE databases were searched through April 2022 to identify RCTs evaluating restrictive versus liberal transfusion in patients with ACS. The primary outcome was MACE at the longest available timepoint.

Results:
In the TRICS AMI population (N=194), a restrictive transfusion strategy did not increase the risk of MACE (OR: 1.36; 95% CI: 0.57-3.27). Three additional RCTs met eligibility criteria for the systematic review yielding a total of 1015 patients. The transfusion strategies were similar across all studies. After synthesizing the data, restrictive transfusion was associated with a trend toward an increased absolute risk of MACE (4%; 95% CI, -1 to 9%) and MI (3%; 95% CI, 0 to 6%) at the longest available timepoint (Figure).

Conclusion:
In the setting of ACS, liberal transfusion strategies may reduce the risk of long term adverse cardiovascular events.
Abstract 10494: Proteomic Assessment of Novel Kidney Function Biomarkers in Heart Failure: A Community Study
Authors: Shearer Joe J , Park Ho Young , Joo Jungnam , Kuku Kayode O , Bielinski Suzette J , Manemann Sheila M , Roger Veronique L
Published: June 2023

Introduction:
Heart failure (HF) is a complex syndrome with high mortality often associated with impaired kidney function. Estimated glomerular filtration rate (eGFR) is central to kidney function assessment in HF. However, novel proteins related to kidney function (lipocalin 2 [LCN2], macrophage inhibitory cytokine 1 [MIC1], T cell immunoglobulin and mucin domain 1 [TIM1]) may improve risk stratification of HF patients, beyond eGFR. Their prognostic contribution remain to be fully explored.

Hypothesis:
Proteomic assessment of kidney function biomarkers improves risk stratification in HF.

Methods:
Clinical data and biospecimens were collected from a HF community cohort in Southeastern Minnesota from 2003-2012. Serum creatinine was measured in 1,388 patients and eGFR was calculated with the 2021 Chronic Kidney Disease (CKD) Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL/min/1.73m
2
. Plasma proteins were measured using the SomaLogic aptamer-based technology SomaScan®. In HF patients with and without CKD, Cox proportional hazard models were used to estimate the association between kidney function biomarkers and mortality, after adjustment for Meta-Analysis Global Group in Chronic HF (MAGGIC) risk score.

Results:
At HF index, patients were on average 75±13 years of age and 48% female. Patients had a median eGFR of 57 mL/min/1.73m
2
and 64% had CKD. Adjusted geometric mean levels of LCN2, MIC1, and TIM1 levels were 20-30% higher in patients with CKD. Patients with CKD were at higher risk of dying (HR 1.6, 95% CI 1.4-1.8). Patients with above median levels of LCN2, TIM1, MIC1 were at higher risk of dying, irrespective of CKD (See Figure).

Conclusions:
In a HF community cohort, several novel kidney function biomarkers provided further risk stratification in patients with and without CKD.