Search Results for: Indicazioni per gli screening oncologici

Circulation, Volume 150, Issue Suppl_1, Page A4143671-A4143671, November 12, 2024. Background:Despite progressively high morbidity and mortality rates associated with severe tricuspid regurgitation (TR), limited treatment options are available.Aims:The single-arm, multicenter, prospective TRISTAR study(K-Clip Transcatheter Annuloplasty System in Tricuspid Regurgitation(TRISTAR) Early Feasibility Study) evaluated the 1-year outcomes of the novel transcatheter K-Clip reconstruction system in treating secondary TR.Methods:Between May 2022 and October 2022, patients with ≥severe secondary TR at 11 centers, despite medication therapy, were deemed candidates for transcatheter tricuspid repair by the local Heart Team and a multidisciplinary screening committee.Results:Ninety-six patients were enrolled(mean age 72.7±7.1 years, 60.4% female, mean TRISCORE 5.3±2.1). Technical success and procedural success were achieved in 97.9% and 93.8%. At 1 year, echocardiography showed average reductions of annular septolateral diameter by 11.3% (41.9mm vs. 37.1mm, p < 0.001) with increases in stroke volume(60.8±18.5mL vs 67.6±19.8mL, p < 0.001) and cardiac output(4.3±1.5 vs 5.3±2.0, p < 0.001). Tricuspid regurgitation was reduced to ≤moderate in 82.5% with ≥1-grade reduction in 97.7% and ≥2-grade reduction in 66.3%. Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (32.6% to 96.5%, p < 0.001). Six-minute walk test increased by 31.9m(304.3±81.2, p

Circulation, Volume 150, Issue Suppl_1, Page A4145678-A4145678, November 12, 2024. Introduction:Calcium scoring computed tomography (CAC) is a widely available and inexpensive modality of screening for atherosclerosis. This study aims to improve the predictive value of CAC by incorporating pericardial fat characteristics in a CatBoost model.Methods:A sample of 7,000 non-contrast clinically indicated CAC scans were randomly selected from a cohort of consecutive Olmsted County MN residents. Known history of atherosclerotic cardiovascular disease or impaired images were excluded. A pericardial fat segmentation model, trained on 191 images of the same dataset with a dice similarity score of 94%, was applied to 6,194 CT scans; Volume and mean Hounsfield unit (mHU) of the output masks were added to age at imaging, radiologist-measured calcium score, male gender, diabetes, and smoking (Figure 1). A 70,20 and 10% split was used to produce the training, validation and test set, respectively. Features were inputted to CatBoost classifier, as the best model tested, to predict four outcomes: acute coronary syndrome (ACS), heart failure (HF), ischemic stroke, and all-cause mortality. Model was evaluated by area under the ROC curve (AUC) on the unseen test set.Results:Mean age was 55.2 (8.8), 55.2 (8.8) and 54.8 (8.5) years in the training, validation and test sets, respectively, and 65%, 67% and 66% of the populations were male. The mean AUC, obtained through bootstrapping with 100 iterations, was 0.81 [0.77-0.85], 0.86 [0.60-0.92], 0.80 [0.73-0.87] and 0.87 [0.81-0.91] for HF, ACS, stroke and death, respectively; The same analysis excluding pericardial fat measurements showed a 3% reduction in the AUC for all of the investigated outcomes (Figure 2).Conclusion:Our study presents a robust risk prediction model for ACS, HF, stroke, and mortality based on CAC scans. The improved performance of the model by incorporating pericardial fat characteristics, highlights the potentials of deep learning in timely inexpensive risk prediction in large populations.

Circulation, Volume 150, Issue Suppl_1, Page A4142443-A4142443, November 12, 2024. Introduction:Abdominal aortic aneurysm (AAA) is a significant cause of morbidity and mortality in older adults. The AAA screening guidelines from the Society of Vascular Surgery include risk factors such as sex, age, smoking, and family history. This study explored whether integration of a polygenic risk score (PRS) and proteomics with clinical data could improve AAA prediction in the ARIC Study.Methods:Over a median follow-up of 24 years from ARIC visit 2 (1990-92) baseline, we identified 487 clinical AAA cases among 9,373 ARIC participants (7,397 Whites and 1,976 Blacks) through hospital discharge diagnoses or death certificates. We selected AAA-associated clinical risk factors based on literature and our expertise, including age, gender, race, field center, smoking status, smoking pack-years, waist girth, BMI, levels of total and HDL cholesterols, hypertension, diabetes, and eGFR. We calculated the PRS[WT1] based on SNP dosage in ARIC and the latest genome-wide association study for AAA, which reported 141 independent associations from 14 discovery cohorts (PMID: 37845353). ARIC used SOMAscan v4 to measure 4,955 plasma proteins at baseline, of which 24 were significantly associated with clinical AAA (p < 1x10^-5) independent of the clinical risk factors. The prediction equation for AAA risk was constructed in 3 Cox regression models: 1) clinical risk factors measured at baseline, 2) model 1 variables plus PRS, and 3) model 2 variables plus the 24 AAA-associated proteins identified through proteomics analysis. We used the area under the curve (AUC) to evaluate the prediction performance of these models for AAA risk.Results:Participants in the top quintile of PRS showed significantly higher AAA risk compared to the lowest quintile (HR 1.41, 95% CI: 1.03 – 1.85) after adjustment for clinical risk factors. Adding the PRS to clinical risk factors did not improve the AUC: 0.890 (95% CI: 0.869 - 0.945) in model 1 vs 0.891 (95% CI: 0.853 - 0.961) in model 2. Further adding the 24 AAA-associated proteins substantially improved the performance of the prediction model [AL2] (AUC=0.950, 95% CI: 0.939 - 0.986 in model 3), with 289 AAA events in the top quintile of predicted risk compared to 12 in the lowest quintile.Conclusion:A proteomics-integrated approach that combined clinical risk factors and proteomics data enhanced AAA risk prediction and has the potential to improve risk stratification and early intervention for AAA.

Circulation, Volume 150, Issue Suppl_1, Page A4124675-A4124675, November 12, 2024. Introduction:The prevalence of hypertrophic cardiomyopathy (HCM) in the UK Biobank based on ICD-10 codes (.07%) is lower than global estimates of disease prevalence (0.2 – 0.5%). Prior studies using this data have remarked on the limitations of findings given likely underdiagnosis. The availability of cardiac MRI scans on a fraction of the participants offers an opportunity to identify missed diagnoses.Aims:This study seeks to utilize a generalizable deep learning model to detect likely cases of undiagnosed hypertrophic cardiomyopathy from cardiac MRIs in the UK Biobank.Methods:The foundational model was trained on a multi-institutional dataset of 14,073 cardiac MRIs via a self-supervised contrastive learning approach that sought to minimize the divergence between scans and their associated radiology reports. The pre-trained model was fine-tuned to diagnose hypertrophic cardiomyopathy on a distinct cohort of 4,870 MRIs with 368 cases of HCM, achieving an AUC of 0.94. The fine-tuned model was applied to the UK Biobank cardiac MRI dataset to ascertain predicted probabilities of HCM. Cases exceeding a threshold of 95% – correlating to the top 0.5% of cases (expected specificity of 97% and sensitivity of 60%) – were screened in for manual reading. In a blinded fashion, a board-certified radiologist was tasked with diagnosing HCM on a sample of cases composed of high and low predicted probabilities.Results:Of the 43,017 patients with cardiac MRIs, only 9 (.02%) had an ICD diagnosis of HCM. 266 cardiac MRIs were manually reviewed: 216 had greater than 95% predicted probability of HCM; 50 negative controls were randomly selected amongst cases with predicted probability less than 10%. The radiologist concurred with an HCM diagnosis for 115 cases (sensitivity 53%, specificity 98%), 112 of which were previously undiagnosed. The prevalence of hypertension and aortic stenosis did not significantly differ between the cohort of true positives (69.2%) and false positives (76.6%). The corrected prevalence of HCM in the UK BioBank MRI cohort is estimated at 0.28%.Conclusions:The findings of this study illustrate the remarkable ability of a generalizable deep learning model to detect undiagnosed cases of a rare disease process from cardiac MRIs. This is an important milestone that may allow for widespread screening of hypertrophic cardiomyopathy while minimizing demand for radiologist labor, and thereby allow patients to reap the substantial benefits of earlier treatment.

Circulation, Volume 150, Issue Suppl_1, Page A4136799-A4136799, November 12, 2024. Introduction:The prevalence of heterozygous familial hypercholesterolemia (HeFH) is 1:250. Untreated individuals have up to a 20-fold increased risk for premature coronary artery disease (CAD). In adults, low socioeconomic status (SES) individuals, bear a disproportionate share of the CAD burden. In this context, we sought to examine the association of social determinants of health and age at HeFH diagnosis and treatment.Methods:We performed a retrospective single-center study of children with HeFH who presented to the Lipid Heart Clinic at the Children’s Hospital of Philadelphia (2012-2022). The primary outcome was age at HeFH diagnosis. The secondary outcome was age at statin initiation. Multivariable linear regression models were used to examine the association between the primary exposure of interest, Child Opportunity Index (COI) and the outcomes. Secondary exposures included race, ethnicity, health insurance, and primary language. To explore potential referral bias, we compared the COI of the study cohort to that of the institution’s catchment area, defined as within a two-hour drive of the primary clinic.Results:We evaluated 577 patients. The median age at presentation was 12 (9, 14) years and the median LDL-C was 199 (169, 235) mg/dL; 58% were prescribed a statin with a median age of statin initiation of 13 (10, 15) years. The median COI for the cohort was 84 (62, 95). There was no association between COI, ethnicity, health insurance, or primary language and the age at HeFH diagnosis or statin initiation. On multivariable analysis, black race was associated with older age at HeFH diagnosis compared to white race (adjusted estimate 1.2 +/- 0.49 yrs, p = 0.014). There was no difference in age at statin initiation by race. Higher LDL-C, male sex, and lower BMI percentile were associated with younger age at statin initiation. The COI distribution of the study cohort was significantly different than that of the catchment area (p < 0.001). 70% of the study cohort were of high and very high COI compared to 57% of the catchment area.Conclusion:Black race was associated with older age at HeFH diagnosis, however, there were no disparities in age at statin initiation. The COI of the cohort was significantly higher than that of the catchment area suggesting that low COI populations are under-referred for HeFH evaluation. Future efforts should focus on improving barriers to universal screening and identifying obstacles to HeFH diagnosis and referrals.

Circulation, Volume 150, Issue Suppl_1, Page A4146638-A4146638, November 12, 2024. Introduction/Background:According to the American Heart Association, the accumulation of plaque in the walls of arteries is identified as the primary cause of atherosclerotic cardiovascular disease (ASCVD). Apolipoprotein B (apo B) has been identified as a more precise cardiovascular risk marker than LDL-C, while high-sensitivity C-reactive protein (hsCRP) has shown potential as a cardiovascular disease indicator.Research Questions/Hypothesis:Goals/Aims:To investigate the diagnostic performance and routine screening cut-off of hsCRP for early ASCVD risk in adult patients, comparing it with Apo B.Methods/Approach:A sample of 494 individuals from the NHANES 2015-2016 laboratory dataset, with a mean age greater than 17 years, was used for this study. ASCVD risk was measured by non-HDL-C, categorized into low and high risk based on the Mayo Clinic reference range. Predictors included apo B, and hs-CRP. Binomial logistic regression and ROC curve analyses were conducted using the generalised linear models and pROC packages in RStudio IDE. Hypotheses were validated at p≤0.05, and diagnostic performance metrics such as ROC AUC, sensitivity, and specificity were measured on a scale of 0-1.Results:The findings revealed that for every 1g/L increase in apo B concentration, the odds of high ASCVD risk were approximately 3.8 ×1011 times higher. Additionally, the model indicated that the odds of high ASCVD risk were 1.03 times higher for every 1mg/L increase in hsCRP concentration. However, this indicates that hsCRP level was not associated with odds of ASCVD risk. The ROC AUC for apo B and hsCRP were approximately 0.9739 and 0.6165, respectively, with cut-off values (sensitivity, specificity) of approximately 0.9g/L (0.927, 0.897) and 2.4 mg/L (0.596, 0.601), respectively. Thus, levels above these thresholds for both apo B and hsCRP are associated with high ASCVD risk.Conclusion(s):The study demonstrates that apo B exhibits high discriminatory and diagnostic accuracy, making it a suitable ASCVD risk biomarker compared to hsCRP. While hsCRP shows moderate diagnostic accuracy, it is not sufficient as a standalone ASCVD risk diagnostic marker. Therefore, apo B could serve as a replacement for LDL-C, while hsCRP could possibly serve as an add-on test in ASCVD risk assessment.

Circulation, Volume 150, Issue Suppl_1, Page A4147236-A4147236, November 12, 2024. Background/Introduction:Adults with congenital heart disease have higher rates of anxiety, depression, and suicide, compared to those without congenital heart disease. A variety of factors contribute to psychological distress among adults with CHD, including functional impairment, neurocognitive deficits, the increasing concerns for reinterventions, body image due to surgical scars or body insecurity. However, screening and targeted treatment is still lacking.Methods/Approach:96 unique patients were seen in ACHD clinic. Each was screened for anxiety and depression using the PHQ-4. Based on the results and clinical findings, 1 of 4 clinical pathways were pursued: 1 negative screening; no consult with a psychologist was recommended; 2 positive PHQ-4 with telehealth follow-up with an in-practice psychologist; 3 PHQ-4 positive with an in-practice psychologist consult during their outpatient visit; 4 already established relationship with a psychologist.Results/Data:Of the unique 96 patients seen in ACHD clinic 6 were excluded for severe developmental delays. Of the remaining 90 patients, 7% (n = 6) had an established relationship with a psychologist. The 84 that did not have an established relationship with a psychologist were screened for anxiety and depression. 49%, ( n = 44) were either seen in clinic by the psychologists and 22%, (n=20) followed up with an outpatient visit. The remaining 22% (n = 20) were screened and had a negative phq-4 with no clinically significant signs of anxiety or depression at that visit.Conclusions:Adults living with CHD have and will continue to encounter unique challenges that extend beyond the physical realm, often grappling with psychological distress that affects their overall well-being and quality of life. While depression has been a focal point in general cardiac research, elevated anxiety levels are equally significant and warrant attention. Within this study, anxiety and depression requiring mental health follow-up was underdiagnosed and undertreated in 76% of the population. Underpinning the need for routine screening for psychological and QOL impairments, as well as ntegration of mental health professionals within ACHD programs.

Circulation, Volume 150, Issue Suppl_1, Page A4142494-A4142494, November 12, 2024. Background:Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting over 59 million individuals worldwide. Even wearable heart rate monitors can detect ongoing AF episodes, but none of the devices are able to assess the susceptibility to impending episodes. The prediction of AF episodes during normal rhythm would significantly improve the early treatment of AF.Research Hypothesis:Heart diseases are known to affect the short- and long-range correlations in beat-to-beat intervals, i.e., RR interval (RRI) time series. The hypothesis is that persistent alterations remain in the RRI correlations even outside of AF episodes. The study examines whether the RRI correlations can indicate the susceptibility to AF during normal rhythm.Methods:We analyze the correlations in RRIs with detrended fluctuation analysis (DFA). We enhance the analysis with its dynamical (DDFA) variant, which assesses time-dependent correlations over several ranges of scale. We attempt to discriminate the AF population with varying ratios of AF episodes (from 99%) from healthy controls by their RRI correlations with XGBoost classifier.Data and results:The data consist of long ECG recordings of 274 healthy controls and 84 patients with AF from Physionet and THEW datasets. The data is split into subclasses according to the relative time of the recording spent in AF: (a) >99% (N=34), (b) 20-99% (N=24), (c)

Circulation, Volume 150, Issue Suppl_1, Page A4146709-A4146709, November 12, 2024. Introduction:Mitochondrial calcium (mCa2+) exchange regulates energy metabolism, but if perturbed causesmCa2+depletion and energy starvation ormCa2+overload and cell death. The mitochondrial sodium (Na+)-calcium exchanger, NCLX, is critical formCa2+efflux in the heart, and animal models support NCLX as a therapeutic target to limit pathogenicmCa2+overload. However, the mechanisms that regulate NCLX activity are largely unknown, representing a key barrier to translation.Goal:We used proximity biotinylation screening to identify the NCLX interactome and define novel regulators of NCLX function.Hypothesis:Our screen identified the mitochondrial inner membrane protein, TMEM65, as an NCLX-proximal protein that potently enhances Na+-dependentmCa2+efflux. Therefore, we hypothesized that TMEM65 promotesmCa2+efflux through NCLX.Approach:We measuredmCa2+exchange in AC16 cardiomyocytes with TMEM65 overexpression (OE) or CRISPR/Cas9 genetic disruption ofTMEM65to test its effect onmCa2+efflux, and used pharmacologic inhibition and genetic knockout to determine TMEM65’s functional dependence on NCLX. We evaluated TMEM65’s impact on murine cardiac functionin vivousing an AAV9-shRNA knockdown strategy.Results:Deletion ofTMEM65attenuated Na+-dependentmCa2+efflux, while inhibition or deletion of NCLX ablated the increase inmCa2+efflux observed with TMEM65 OE. Proximity ligation assay revealed co-localization of TMEM65 and NCLX in intact cells.In silicomolecular modeling and co-fractionation of NCLX and TMEM65 via size-exclusion chromatography support their existence in a common macromolecular complex. Mutagenesis studies identified residues N163/D167 as critical to TMEM65 function, suggesting their importance to its cooperation with NCLX.TMEM65expression decreased in human and murine heart failure, andTmem65KD in mice promoted myocardialmCa2+overload and impaired cardiac function. Notably, TMEM65 OE mitigated necrotic cell death during cellular Ca2+-overloadin vitro.Conclusions:Loss of TMEM65 function disrupts NCLX-dependentmCa2+efflux, causing pathogenicmCa2+overload, cell death and organ-level dysfunction, whereas gain of TMEM65 function can attenuate these effects. Our findings demonstrate the essential role of TMEM65 in maintainingmCa2+efflux and suggest modulation of TMEM65 as a novel therapeutic strategy to controlmCa2+homeostasis in heart failure and other pathologies featuring dysregulatedmCa2+exchange.

Circulation, Volume 150, Issue Suppl_1, Page A4146053-A4146053, November 12, 2024. Introduction:Cardiomyopathy (CM) and myocarditis rank as the fifth leading cause of death and disability in G20 countries amongst all cardiovascular disease related (CVD) deaths. Despite their escalating burden, there is a notable lack of consistent data across these nations. This study is the first to estimate the burden of these cardiac conditions over the last three decades, including the initial two years of the COVID-19 pandemic, highlighting the urgent need for improved surveillance and specific healthcare strategies to manage these critical health issues.Method:We estimated incidence, prevalence, deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs) due to CM and myocarditis by age, sex, year and location across the G20 countries from 1990-2021 using global burden of disease 2021 methodology.Results:From 1990 to 2021, the total percentage change (TPC) in prevalence counts increased by 64% (95% Uncertainty Interval: 53% to 75%), incidence by 57% (47% to 68%), and deaths by 37% (26% to 49%). Japan had the highest age-standardized incidence rate (ASIR) at 19.84 (16.38-24.21) cases per 100,000, closely followed by Sweden at 19.74 cases per 100,000. The highest mortality rate (ASMR) was observed in Latvia at 27.95 (23.89-31.99) cases per 100,000, with Russia following at 26.3 cases per 100,000 in 2021. Poland recorded the highest YLD rate (ASYLDR) at 16.13 (11.05-22.86), with Sweden next at 15.67 per 100,000 in 2021. The highest incidence occurred in the 70-74 age group with 76,173 cases (46,415-113,840), with the most deaths in the 80-84 age group at 31,289 (27,390-33,741), and the highest DALYs in the 55-59 age group at 750,723 (680,540-814,890) in 2021. Regarding gender, the TPC in incidence for males was 55% compared to 61% for females, in deaths 57% for males versus 16% for females, and in YLDs 67% for males versus 54% for females from 1990 to 2021.Conclusion:Deaths due to CM and myocarditis accounted for 2.04% of all CVD deaths in G20 countries in 2021. The increasing burden highlights the need of proactive initiatives, including tailored health education and advanced screening programs. It should be prioritized to address the needs of the most affected demographics and regions. Integrating technology and cross-border healthcare collaborations could play a pivotal role in mitigating the impact of this condition and enhancing overall public health resilience.

Circulation, Volume 150, Issue Suppl_1, Page A4137986-A4137986, November 12, 2024. Background:Clinical trial screening is labor-intensive, time-consuming, and error prone. We have developed RECTIFIER, an AI-based clinical trial screening tool, to enhance the efficiency and accuracy of patient recruitment. This study aims to evaluate RECTIFIER’s effectiveness compared to manual screening in a randomized implementation study.Methods:This study was designed as an implementation study as part of an active heart failure trial named COPILOT-HF (NCT05734690). Potential eligible patients were identified via a structured electronic medical record query and randomized to be screened for clinical trial eligibility either by RECTIFIER or manually by clinical staff. The outcome measures included the number of patients contacted, and the number of patients reached for clinical trial enrollment. Data was collected over a period of 3 months.Results:A total of 3834 patients were included in the study, with 1919 patients randomized to the RECTIFIER group and 1915 patients to the manual screening group (Figure). Study staff could manually screen only 1367 patients at the end of the 3-month period. RECTIFIER identified more eligible patients compared to manual screening (833[43.4%] vs. 284[14.8%], p

Circulation, Volume 150, Issue Suppl_1, Page A4138426-A4138426, November 12, 2024. Background:Geographic inequities in cardiovascular mortality are pervasive in the US. Pandemic-related delays in screening and treatment, economic loss, and worsening social determinants may have widened geographic disparities in cardiometabolic health, particularly in states that were hardest hit by these spillover effects. Understanding changes in state-based inequities could inform targeted public health efforts to advance cardiovascular health.Questions:Did the prevalence of cardiometabolic risk factors (diabetes, hypertension, hyperlipidemia, obesity) and lifestyle factors (alcohol consumption, physical inactivity, tobacco use) change between 2011 and 2021? How did between-state differences change over this period?Methods:We included adults from the CDC’s Behavioral Risk Factor Surveillance System. Survey-weighted logistic regressions models were used to calculate age and sex-adjusted risk difference between states with the highest and lowest adjusted prevalence rates of each risk factor in 2011 and 2011, respectively. An interaction term for state and year was included to assess for differential changes in between-state disparities.Results:From 2011 to 2021, there were increases in the age- and sex-adjusted prevalence of diabetes (10.9% [95% CI, 10.7,11.0] to 12.4% [12.2,12.6]), hypertension (32.4% [32.1,32.7] to 33.7% [33.4,34.0]), and obesity (27.5% [27.2,27.7] to 33.1% [32.8,33.5]). Geographic inequities widened, with increases in the difference between states with the highest vs lowest prevalence of diabetes (5.7% [5.3,6.1] to 7.8% [7.3,8.3]), hypertension (14.2% [13.6,14.8] to 17.2% [16.4,17.9]) and obesity (14.3% [13.6,15.0] to (15.7% [14.7,16.7])(Table).The prevalence of alcohol consumption (18.0% [17.7,18.2] to 15.6% [15.3,15.8]), physical inactivity (25.7% [25.4,27.4] to 24.0% [23.6,23.7]), and tobacco use (44.9% [44.5,45.3] to 36.3% [35.8,36.8]) decreased, and between-state differences did not widen.Conclusion:In this national study, the prevalence of hypertension, obesity, and diabetes increased from 2011 to 2021, and state-based inequities widened. Our findings highlight the urgent need for public health interventions to address widening state-based disparities in cardiometabolic health.

Circulation, Volume 150, Issue Suppl_1, Page A4139767-A4139767, November 12, 2024. Background:Cardiac allograft vasculopathy (CAV) is a heterogenous and poorly understood process of immune and non-immune factors occurring within the coronary artery and a leading cause of graft failure in heart transplant recipients. Intravascular ultrasound (IVUS) is used as an adjunct to angiography to significantly increase the sensitivity for detection disease, however by current standards < 1% of IVUS images are graded for maximal intimal thickness (MIT) or scored for severity of CAV. The majority of IVUS frames remain unanalyzed.Aims:Demonstrate the application of pre-trained DeepIVUS machine learning model to annotate IVUS images obtained from transplant patients, establishing the accuracy of this tool in a new patient population.Methods:We reviewed 963 clinically annotated IVUS frames from heart transplant recipients, 706 were selected after screening for completeness. DeepIVUS was used to segment the frames and create predictions of the vessel lumen, plaque area and intimal thickness (IT) measurements around the entire vessel lumen. To compare with expert annotations, typically a single caliper measurement, the 90th percentile value of DeepIVUS-predicted IT was used. A confusion matrix was used to assess the model's ability to accurately classify predicted and true IT values, utilizing a threshold of 0.5 mm.Results:In 163/706 frames (23.1%), DeepIVUS labeling resulted in segments with jagged or non-physiologic shapes. These were automatically discarded using a quantitative ovalness criteria, Figure 1. Agreement between DeepIVUS predicted MIT and expert measured MIT in the remaining 543 frames yielded a strong Pearson correlation coefficient of 0.81 with an R2 of 0.65, Figure 2A. The linear fit was used to determine the DeepIVUS IT cutoff (0.554mm) which corresponded to clinical cutoff of 0.5mm. Using this value, DeepIVUS correctly classified 86.6% of frames (sensitivity 85.1%, specificity 87.9%, aF1 0.86), Figure 2B.Conclusion:We present a first use applcation of a pre-trained Deep IVUS image analysis in a transplant population demonstrating good agreement with expert clinical annotation. In current practice, a small fraction of images from each IVUS study are annotated. With an ovalness criteria providing quality control, DeepIVUS may be applied to non-annotated frames, allowing significantly more frames per IVUS study to be analyzed. Future studies are warranted to understand the prognostic capabilities of these automated annotations.

Circulation, Volume 150, Issue Suppl_1, Page A4139898-A4139898, November 12, 2024. Background:Tachycardia can drive heart failure (HF). Traditionally, this is experimentally modeled using an implantable pacemaker, an invasive, technically demanding, and low-throughput methodology. Genetically-expressed light-activated ion channels (‘optogenetics’) provide an alternative approach forin vivocardiac stimulation, which if applied in transparent zebrafish embryos, may be used for non-invasive, cost-effective, high-throughput HF and drug screening studies.Objective:Establish a non-invasivein vivoexperimental model of HF using optogenetic tachypacing in larval zebrafish.Methods:Larval zebrafish expressing cation-nonspecific channelrhodopsin-2 (ChR2), chloride-specific anion channelrhodopsin-1 (ACR1), or green fluorescent protein (GFP, as a light-exposed, non-paced control) in cardiomyocytes were exposed to intermittent tachypacing (15s on, 15s off) by programmed light pulses from 2-7 days post fertilization (dpf). At 7 dpf: (i)in vivoatrial and ventricular mechanical function was assessed by end-diastolic area (EDA), end-systolic area (ESA), and ejection fraction (EF) with video microscopy; (ii) cardiac structure was measured by atrial and ventricular area in fixed larvae with fluorescent imaging; and (iii) gene expression of cardiac-specific HF biomarkers (atrial and brain natriuretic peptide [anp,bnp], atrial- and ventricular-specific myosin heavy chain-a and -b [myh6,myh7], and a-smooth muscle actin [acta2]) was quantified by qPCR. Values across groups were compared by one-way ANOVA, with Šídákpost hoctests.Results:In vivo, atrial and ventricular EDA were greater in ChR2 (+191%,p

Circulation, Volume 150, Issue Suppl_1, Page A4144298-A4144298, November 12, 2024. Background:Microvascular dysfunction is a hallmark of hypertrophic obstructive cardiomyopathy (HOCM). Factors modulating myocardial microcirculation in response to disease phenotype require further studies. This study aims to investigate microvascular remodeling in HOCM patients using a quantitative imaging toolset that combines classical histological screening, ultrastructure assessment, 3D molecular imaging and automated segmentation of myocardial tissue specimens.Methods:Microvascular remodeling was studied in a cohort of 20 consecutive HOCM patients who underwent septal myectomy, and 6 normal controls. Myectomy specimens were examined using histopathological staining, immunofluorescence and electron microscopy. Molecular 3D visualization was conducted using Free of Acrylamide SDS-based Tissue Clearing (FASTClear) protocol of 300 µm thick myocardial slices. Cleared slices were examined using immunostaining targeting microvascular markers; Isolectinβ4 and CD31. Reconstructed images of stained slices were analyzed using ImageJ and Python-based algorithm. Transcriptome data from HOCM patients’ myocardial tissues was analyzed to investigate angiogenesis and hypoxia-related gene expression. Gene and protein expression was validated using RT-PCR and immunohistochemical staining.Results:Histopathological examination demonstrated a significant increase in perivascular fibrosis around intramural vessels in HOCM myocardial tissues, compared to controls, associated with a significant increase in vascular wall thickness, which led to a reduction in luminal area. Electron microscopy analysis revealed, for the first time, ultrastructural changes in the microvasculature in HOCM, including irregular microvessels, disorganized perivascular collagen fibres and abnormal endothelial cell morphology. Increased Aurora and Caspase 3 levels in the endothelial cells of myocardial microvessels were observed. 3D molecular imaging of myocardial slices showed a significant reduction in microvascular density, length, and number of microvascular branches in HOCM, which correlated to LVOT. Microvascular orientation was significantly altered throughout slices of HOCM myocardium. Transcriptome data analysis and protein examination revealed that angiogenesis and hypoxia-related markers elevate in HOCM patients’ myocardial tissues.Conclusion:Structural alterations of coronary microvasculature delineate the clinical presentation and myocardial functional response in HOCM patients.

Circulation, Volume 150, Issue Suppl_1, Page A4145628-A4145628, November 12, 2024. Introduction:Lipoprotein A (LpA), an inherited, soluble protein formed in the liver, may be useful as a risk stratification tool for atherosclerosis. Asymptomatic atherosclerosis with a high tendency to rupture is known as vulnerable plaques, which can be defined with common morphologies such as thin-cap fibro-atheroma with a thin layer of depleted smooth muscles (TCFA) or a lipid-rich (LR) plaque.Hypothesis:A high LpA level is associated with an increased risk of vulnerable plaques, defined as TCFA or LR plaque.Methods:A systematic search of PubMed, SCOPUS, and Embase databases was conducted to find and include relevant observational studies that compared LpA levels with two primary outcomes of plaque vulnerability, TCFA or lipid-rich plaques. A total of 196 studies were identified, 67 underwent initial screening, and 15 were assessed for full-text eligibility. The random effects model was used to pool binary outcomes as odds ratios (OR) with 95% confidence intervals (CI), and the results were presented on forest plots. Sensitivity analysis was performed using the leave-one-out method, and heterogeneity was identified using I2 statistics. Publication bias was assessed using the Luis Furuya-Kanamori (LFK) index.Results:A total of 6 studies were included in our analysis, comprising three retrospective cohort studies and three prospective cohort studies involving 806 patients, out of which 503 were defined as low LpA and 303 as high LpA. Our analysis revealed that high LpA levels were associated with greater odds for both TCFA (OR 2.61 95% CI:1.30-5.24, p