Risultati per: Screening del cancro al seno nelle donne

Circulation, Volume 150, Issue Suppl_1, Page A4131439-A4131439, November 12, 2024. Background:Evidence linking social isolation to cardiovascular disease morbidity and mortality has grown in recent years. Still, information on how this may manifest in real world settings and its implications for screening practices is limited. In 2019, our large national integrated health care system implemented screening for social isolation as part of a broader universal social risk assessment. This repository of screening data was joined to administrative claims to test these associations in real world data and explore differences by demographic and medical factors.Methods:Social isolation responses recorded from 2019-2022 were included for a cohort of adult health plan members with documented atherosclerotic cardiovascular disease (ASCVD). We selected a single random assessment for each member and retained any other responses for sensitivity analyses. Cohort members had at least 10 months of enrollment surrounding assessment date for use as the baseline period and were followed for 365 days. We used cox proportional hazards regression with right censoring for coverage gaps to estimate the risk of all-cause mortality conferred by social isolation. We used Poisson regression to model the rate of inpatient stays.Results:There were 881 deaths among 7,484 members (18% of those with social isolation; 11% of those without). The isolated group skewed less male (54% vs. 65%, p

Circulation, Volume 150, Issue Suppl_1, Page A4143150-A4143150, November 12, 2024. Background:The FACTOR-64 study was a randomized controlled trial designed to assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in high-risk patients with diabetes followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes. Results at four years showed a lower revascularization rate (3.1% (14) vs. 8.9% (40), p

Circulation, Volume 150, Issue Suppl_1, Page A4144730-A4144730, November 12, 2024. Background:A personalized, non-invasive assessment approach for evaluating the risk of obstructive coronary artery disease (CAD) is crucial for patients with an intermediate or low clinical likelihood of CAD before undergoing invasive coronary angiography (ICA). This method allows clinicians to effectively rule out the presence of obstructive CAD without the need for ICA or to determine if a referral for ICA is warranted. Emerging lipidomics biomarkers may be valuable in this process. However, technological challenges in detecting structurally similar lipids and the requirement for advanced computational tools have so far impeded the clinical application of lipidomics research.Hypothesis:Our study aims to develop an innovative non-invasive diagnostic test utilizing novel lipidomics biomarkers, potentially revolutionizing current risk classification schemes for CAD.Methods:In this post-hoc analysis of the CorLipid trial (NCT04580173), we employed extreme gradient boosting (XGBoost) machine learning to assess the predictive power of a lipidomics panel for obstructive CAD risk. Liquid chromatography-mass spectrometry analyzed lipid profiles from 146 individuals undergoing ICA. SYNTAX Score (SS) was used to define obstructive CAD as SS >0 versus non-obstructive CAD (SS=0).Results:Of the 146 participants (25% female, mean age: 61 ±11 years old), 55% had obstructive CAD (SS >0). Lipidome changes [phosphatidylinositols, (lyso-)phosphatidylethanolamine, (lyso-)phosphatidylcholine, triglycerides, diglycerides, and sphingomyelins] were investigated to identify lipids potentially associated with the phenotype and complexity of CAD. Using this information, 290 quantified serum lipid species were utilized to develop an XGBoost algorithm with 17 serum biomarkers ( consisting of sphingolipids, glycerophospholipids, triacylglycerols, galectin-3, glucose, low-density lipoprotein, and lactate dehydrogenase) with very good discriminative ability [ROC AUC: 0.875 (95%CI: 0.867-0.883)], excellent sensitivity (100%) but moderate specificity (62.1%) for the prediction of obstructive CAD.Conclusions:These findings indicate that a deep-learning-based non-invasive diagnostic test, using lipidomics serum biomarkers, could reliably rule-out obstructive CAD without necessitating ICA. To enhance generalizability, these results should be validated in larger and similar cohorts. Further research, particularly leveraging machine learning, is promising for refining risk stratification.

Circulation, Volume 150, Issue Suppl_1, Page A4138955-A4138955, November 12, 2024. Introduction:Rheumatic heart disease (RHD) is the most common acquired heart disorder in children and adolescents worldwide. We developed and validated an automated artificial intelligence (AI)-guided RHD screening algorithm adapted for point-of-care ultrasonography (POCUS) in school-aged children.Methods:We employed a cross-domain transfer learning approach, in which a 3D convolutional neural network (CNN) was first trained to detect structural RHD deformation of the mitral or aortic valves in 244,523 videos, representing all views from 5,614 adult transthoracic echocardiograms (1:5 age and sex-matched cases and controls; median age 69 [58-80] years, 76.4% female) in a large US health system. The model was fine-tuned for stage ≥B (“definite”) RHD in 21,472 POCUS videos (2D parasternal and apical acquisitions) from 5,525 studies (75% training, 25% validation) in a pediatric screening program (median age 11 [IQR 10-13] years, 54.6% female) in Brazilian low-income schools. Testing was performed in a held-out set of 1,966 parasternal long-axis (PLAX) videos from 1,138 studies in Brazil (14 [1.2%] with stage ≥B RHD) as well as in an external pediatric screening set in Uganda consisting of 249 videos from 96 studies (34 [35.4%] with stage ≥B RHD) (Fig. 1).Results:Our model (Fig. 2) achieved a study-level AUROC (area under the receiver operating characteristic curve) of 0.88 across the held-out/external testing sets for identifying stage ≥B RHD from cardiac POCUS (Fig. 3A). On a video-level the model learned a continuous spectrum of phenotypes on PLAX acquisitions spanning stage ≥B (“definite”) and stage A (“borderline”) cases, ranging from a median video-level AI probability of 0.13 [0.01-0.73] for stage ≥B to 0.00 [0.00-0.01] for non-RHD POCUS (Fig. 3B). At the threshold that maximized Youden’s J in the held-out Brazil set, our algorithm’s performance in the set from Uganda showed 97% recall (sensitivity), a positive predictive value (precision) of 46%, and a negative predictive value of 95%.Conclusions:A transfer learning approach that employs multi-view learning achieves excellent performance for RHD on single-view two-dimensional cardiac POCUS without Doppler. Our study suggests a scalable approach to AI-enabled RHD detection with images that can be acquired by individuals with modest training.

Circulation, Volume 150, Issue Suppl_1, Page A4140219-A4140219, November 12, 2024. Background:Poor healthcare access results in late- or non-diagnosis of rheumatic heart disease (RHD), perpetuating the burden of RHD in low-resource settings. The ADUNU program, a partnership with the Ugandan Ministry of Health in Kitgum, Uganda, aims to improve RHD case detection through decentralized screening led by primary care nurses, who independently perform and interpret brief screening echocardiograms using handheld echocardiography.Hypothesis:We hypothesized ADUNU’s simplified screening protocol would achieve sensitivity and specificity greater than 80% on confirmatory evaluation.Aim:To determine the health system impact of deploying a novel RHD screening protocol into the public health system in Uganda through a cross-sectional study of diagnostic accuracy.Methods:Primary healthcare nurses, certified to perform echocardiographic screening using a single parasternal long axis view in 2D and color Doppler, integrated screening into their clinical and outreach workflows. Community members with positive screens (mitral regurgitation jet ≥2cm or aortic regurgitation jet ≥1cm) were referred for confirmatory echocardiograms at the District Hospital. A random subset with negative screens were recruited for confirmatory echocardiograms at the time of screening as well. Sensitivity, specificity, predictive values, likelihood ratios, accuracy, and agreement (Cohen’s kappa) were calculated between the screening protocol and the confirmatory results.Results:Between May 2023 and April 2024, 3020 community screenings (ages 5-70 years) were conducted by 19 certified nurses. Among 113 positive screens, 61 (53.9%) were confirmed to have RHD. Among 430 negative screens, 14 (3.3%) had RHD. Screening sensitivity was 82.4% (95% CI 72.2-89.4%) and specificity 89.1% (85.9-91.6%). Positive and negative predictive values were 54.5% (45.2-63.4%) and 97.0% (94.9-98.2%). Likelihood ratios were 7.55(+) and 0.19(-). Accuracy was 88.3% (85.2 – 91.4%) and kappa was 0.59 (0.49-0.68).Conclusions:ADUNU’s novel approach to RHD active case finding achieved acceptable diagnostic performance. Nurse-led RHD screening programs that are integrated into routine clinical care shows potential for use in a comprehensive public health program. Very few RHD cases were missed, and under two referrals were generated for every positive case, an acceptable false positive rate. Further economic evaluation is underway to understand the budgetary impact and cost-effectiveness of this program.

Circulation, Volume 150, Issue Suppl_1, Page A4138647-A4138647, November 12, 2024. Introduction/Background:We previously demonstrated that an open-source deep learning model (CXR-CVD Risk) can predict 10-year major adverse cardiovascular events (myocardial infarction&stroke), based on a chest radiograph image (CXR). As deep learning models are black boxes, establishing the biological processes the model captures to predict risk may help build understanding and trust in the model.Research Questions/Hypothesis:To test associations between deep-learning derived CXR-CVD Risk and markers of cardiovascular disease including coronary artery calcium (CAC) and stenosis ≥50% on CT, systolic blood pressure (SBP), ankle brachial index (ABI), and prevalent myocardial infarction and stroke.Methods/Approach:We conducted external validation of CXR-CVD-Risk in two cohorts: 1) 2,097 volunteers in the Project Baseline Health Study (PBHS) and 2) 1,644 Mass General Brigham Biobank (MGBB) patients. The CXR-CVD-Risk model estimated 10-year cardiovascular event risk (probability between 0 and 1) from a CXR image. We calculated linear associations with SBP, ABI, and the logarithm of coronary artery calcium and odds ratios for prevalent hypertension, myocardial infarction, stroke, and, in the MGBB, coronary artery stenosis ≥50%. Analyses were adjusted for age, BMI, sex, smoking status, and enrolling site.Results/Data:CXR-CVD-Risk was associated with CAC in both populations (PBHS: 1.11-fold increase, 95% CI: [1.07-1.16]; MGBB: 1.03-fold increase [1.01-1.05] in CAC per 1% increase in CXR-CV-Risk). CXR-CVD-Risk was also associated with SBP (0.59 mmHg increase [0.24-0.93] in SBP per 1% increase in CXR-CV-Risk), history of hypertension, history of myocardial infarction, and stroke. There was an inverse association with ABI (0.010 decrease [0.005-0.014] in ABI) in the PBHS. In the MGBB, CXR-CVD-Risk was associated with coronary artery stenosis ≥50% (OR = 1.004 [1.002-1.007]). All estimates are after covariate adjustment.Conclusion:This deep learning CXR risk score was associated with coronary artery disease (calcium score and stenosis ≥50%), CVD risk factors, and prevalent CVD. Opportunistic screening using CXRs in the electronic record can identify patients at high risk of CVD who may benefit from prevention.

Circulation, Volume 150, Issue Suppl_1, Page A4147292-A4147292, November 12, 2024. Background:Tissue hypoxia and chronic anemia associated with sickle cell disease (SCD) leads to structural and physiological alterations in the heart. Early detection of heart failure (HF) in patients with SCD can assist with timely interventions, but current methods (e.g., echocardiogram and heart MRI) are not easily accessible in resource-deprived settings. The integration of artificial intelligence (AI)-powered tools utilizing low-cost ECG data to increase the power to detect more patients eligible for early treatment, thus improving patient outcomes, and needs to be validated.Hypothesis:We hypothesize that ECG-AI models developed to detect incident HF in the general population can detect HF in SCD patients.Methods/Approach:We previously developed an ECG-AI model employing convolutional neural networks to classify patients with HF using a large ECG-repository at Wake Forest Baptist Health (WFBH). This model was developed using 1,078,198 digital ECGs from 165,243 patients, 73% White, 19% Black, and 52% female individuals, with a mean age (SD) of 58 (15) years. The hold-out AUC of this previous model in distinguishing ECGs of HF patients from controls was 0.87. In this study, we externally validated this ECG-AI model using SCD patients’ data from the University of Tennessee Health Science Center (UTHSC). Additionally, a logistic regression (LR) model was constructed in the UTHSC cohort by incorporating other simple demographic variables with the outcome of ECG-AI model.Results/Data:The UTHSC external validation cohort included data from 2,107 SCD patients (188 HF and 1,919 SCD patients with no HF), 98% were Black, 72% were female, with a mean age of 39 (14) years. Despite demographic differences between the validation (more Blacks) and derivation cohorts (lower age), our ECG-AI model accurately identified HF with an AUC of 0.80 (0.77-0.82) in the UTHSC SCD cohort. When incorporating ECG-AI outcome (an ECG-based risk value between 0 and 1), age, sex, and race in a LR model, the AUC significantly improved (DeLong Test, p

Circulation, Volume 150, Issue Suppl_1, Page A4142502-A4142502, November 12, 2024. Background:AI-ECG is a cost-effective tool for left ventricular dysfunction (LVD) screening. However, its cost-effectiveness for other forms of structural heart disease (SHD) is unknown. While AI-ECG is inexpensive, a drawback is low positive predictive value (PPV), which leads to high costs from unnecessary follow-up tests. Therefore, strategies to improve the yield of AI-ECG-based screening are needed.Aim:To evaluate the cost savings of a stepwise approach to SHD screening with AI-ECG followed by POCUS compared to AI-ECG alone.Methods:286 adult outpatients undergoing AI-ECG were selected at random. Participants received same-day POCUS and had a recent TTE (our gold standard for SHD). We evaluated four SHDs: aortic stenosis (AS), cardiac amyloidosis (CA), HCM, and LVD. The costs of AI-ECG ($75) and TTE ($1,305) were obtained from Healthcare Bluebook. The cost of POCUS ($100) was estimated independently. Cost savings were analyzed for simultaneous screening for all forms of SHD and screening for individual SHDs.Results:AI-ECG identified potential SHD in 125 patients, but only 39 were true positives by TTE (31% PPV). In AI-ECG positive patients, POCUS demonstrated findings of SHD in 52/125. Compared to TTE, this stepwise approach yielded 32 true positives and 20 false positives (62% PPV). The cost per patient diagnosed with SHD was $4,733 with AI-ECG alone but decreased to $3,182 with stepwise screening (33% cost savings). Screening for individual SHDs resulted in cost reduction from $18,724 to $6,315 (66% savings) for AS, $21,023 to $12,230 (42% savings) for CA, $9,883 to $6,175 (38% savings) for HCM, and $4,019 to $3,582 (11% savings) for LVD.Conclusions:Stepwise screening for SHD with AI-ECG followed by POCUS significantly reduces costs compared to AI-ECG alone. We also suggest a model for parallel screening for multiple SHDs, which is likely more cost-effective than screening for individual SHDs.

Circulation, Volume 150, Issue Suppl_1, Page A4144283-A4144283, November 12, 2024. Introduction:Pulmonary arterial hypertension (PAH) remains an underrecognized, fatal disease. Limited awareness, non-specific symptoms, and late referral to accredited PH centers all contribute to an overall poor prognosis. The previously validated Virtual Echocardiography Screening Tool (VEST) uses 3 routine transthoracic echocardiogram (TTE) parameters (left atrial size, transmitral E:e’ and systolic interventricular septal flattening) to recognize a high PAH likelihood. A positive VEST score has been shown to have 80% sensitivity and 76% specificity for PAH hemodynamics, while a VEST score of +3 has 92.7% specificity for PAH hemodynamics with a positive predictive value of 88.0%.Aim:We aimed to implement a novel algorithm via our electronic medical record (EMR) as an automated VEST calculator to identify patients with a high likelihood of PAH.Methods:An automated EMR VEST calculator was applied retrospectively to 4,952 patients who underwent TTE with TR velocity >/= 2.9 m/s at an accredited PH center from 12/2021-8/2023. Automated EMR VEST scores were validated by comparison to 60 manually scored echocardiograms. Those with VEST score of +3 (highest risk for PAH) underwent chart review to identify whether they were seen by a PH specialist.Results:There was 100% correlation between the automated EMR VEST scores and the manual results.Of the 4,952 patients, 1,655 had a positive automated EMR VEST score, and 355 had a score of +3, predicting the highest likelihood of PAH and warranting urgent referral to an accredited PH center. Of those patients with a +3 score, 103 (29.0%) were never seen by a PH specialist (Fig 1).Conclusion:VEST is a validated, noninvasive and accessible screening tool for identification of patients with a high likelihood of PAH likely to benefit from early referral to a PH center. We present a novel, accurate, and automated EMR algorithm for determination of the VEST score to prompt urgent referral for PH expert evaluation and timely initiation of complex medical therapies. These findings highlight the potential of future artificial intelligence and machine-learning applications for improved recognition of life-threatening PAH.

Circulation, Volume 150, Issue Suppl_1, Page A4144083-A4144083, November 12, 2024. Background:The AI-CVD initiative aims to extract all useful opportunistic screening information from coronary artery calcium (CAC) scans and combines them with traditional risk factors to create a stronger predictor of cardiovascular diseases (CVD). These measurements include cardiac chambers volumes (left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV), and left ventricular mass (LVM)), aortic wall and valvular calcification, aorta and pulmonary artery volumes, torso visceral fat, emphysema score, thoracic bone mineral density, and fatty liver score. We have previously reported that the automated cardiac chambers volumetry component of AI-CVD predicts incident atrial fibrillation (AF), heart failure (HF), and stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). In this report, we examine the contribution of other AI-CVD components for all coronary heart disease (CHD), AF, HF, stroke plus transient ischemic attack (TIA), all-CVD, and all-cause mortality.Methods:We applied AI-CVD to CAC scans of 5830 individuals (52.2% women, age 61.7±10.2 years) without known CVD that were previously obtained for CAC scoring at MESA baseline examination. We used 10-year outcomes data and assessed hazard ratios for AI-CVD components plus CAC score and known CVD risk factors (age, sex, diabetes, smoking, LDL-C, HDL-C, systolic and diastolic blood pressure, hypertension medication). AI-CVD predictors were modeled per standard deviation (SD) increase using Cox proportional hazards regression.Results:Over 10 years of follow-up, 1058 CVD (550 AF, 198 HF, 163 stroke, 389 CHD) and 628 all-cause mortality events accrued with some cases having multiple events. Among AI-CVD components, CAC score and chamber volumes were the strongest predictors of different outcomes. Expectedly, age was the strongest predictor for all outcomes except HF where LV volume and LV mass were stronger predictors than age. Figure 1 shows contribution of each predictor for various outcomes.Conclusion:AI-enabled opportunistic screening of useful information in CAC scans contributes substantially to CVD and total mortality prediction independently of CAC score and CVD risk factors. Further studies are warranted to evaluate the clinical utility of AI-CVD.

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 A4141994-A4141994, November 12, 2024. Background:Screening trials for atrial fibrillation (AF) have produced mixed results; however, it is unclear if there is a subset of individuals for whom screening would be effective. Identifying such a subgroup would support targeted screening.Methods:We conducted a secondary analysis of VITAL-AF (NCT03515057), a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup that would benefit from screening (i.e., heterogenous screening effects). First, we use a potential outcomes framework to develop an effect-based model. Specifically, we predicted the likelihood of AF diagnosis under both screening and usual care conditions using LASSO, a penalized regression method. The difference between these probabilities was the predicted screening effect. Second, we used the CHARGE-AF score, a validated AF risk model. We used interaction testing to determine if the observed diagnosis rates in the screening and control arms were statistically different when stratified by decile of the predicted screening effect and predicted AF risk.Results:Baseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). On average, screening did not significantly increase the AF diagnosis rate (2.55 vs. 2.30 per 100 person-years, rate difference 0.24, 95%CI -0.18 to 0.67). Patients in the highest decile of predicted screening efficacy (n=3026, 10%) experienced a large and statistically significant increase in AF diagnosis rates due to screening (6.5 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28; interaction p-value 0.038) (Figure 1). In this group, the mean age was 84 years and 68% were female. Participants in the highest decile of AF risk using the CHARGE-AF score did not have a statistically significant increase in AF diagnosis rates due to screening (Figure 2). Predicted screening effectiveness and predicted AF risk were poorly correlated (Spearman coefficient 0.13).Conclusions:One-time screening may increase AF diagnoses in a subgroup of older adults with the largest predicted screening effect. In contrast, predicted AF risk was a poor proxy for predicted screening efficacy. These data caution against the assumption that high AF risk is necessarily correlated with high screening efficacy. Prospective studies are needed to validate whether AF screening is effective in the subgroup identified in this study.

Circulation, Volume 150, Issue Suppl_1, Page A4145524-A4145524, November 12, 2024. Introduction:White-coat hypertension (WCH) and masked hypertension (MH) complicate accurate blood pressure (BP) monitoring. While ambulatory BP monitoring (ABPM) is effective, its high cost and limited availability are significant barriers.Hypothesis:We hypothesized that a machine learning (ML) model using clinical data from a single outpatient visit could accurately predict WCH and MH.Aims:This study aimed to develop and validate ML-based prediction models for WCH and MH using accessible clinical data to improve diagnostic efficiency and accessibility.Methods:We enrolled patients from two hypertension cohorts, after excluding those with incomplete data. Patients were classified by office BP and ABPM readings per American Heart Association guidelines. ML models, including Multi-layer Perceptron （MLP）, Support Vector Machine (SVM), and Tabular Prior-Data Fitted Network (Tab-PFN), were developed. Input parameters included demographic data (age, gender, height, weight, smoker), and office BP (OBP) and heart rate measurements. Principal Component Analysis (PCA), kernel PCA (kPCA), or t-distributed stochastic neighbor embedding (t-SNE) were used to improve class separability.Results:The study population comprised 1481 participants with a mean age of 47.6 years (SD 13.6), 65% of whom were male and 20.1% were smokers. OBP measurements showed a mean systolic BP (SBP) of 128.7 mmHg (SD 15.4) and a mean diastolic BP (DBP) of 84.2 mmHg (SD 11.6). ABPM showed a mean 24-hour systolic BP of 122.5 mmHg (SD 11.8) and diastolic BP of 79.3 mmHg (SD 10.1). The inclusion of demographic and OBP data, along with advanced resampling and dimensionality reduction techniques, significantly improved the model’s predictive ability. The final TabPFN model achieved the best performance with recall, precision, F1 score, and accuracy of 0.747, 0.931, 0.829, and 0.807 for WCH, and 0.713, 0.954, 0.816, and 0.907 for MH.Conclusion:Our ML-based model effectively predicts WCH and MH using accessible clinical data, offering a cost-effective alternative before applying ABPM.

Circulation, Volume 150, Issue Suppl_1, Page A4140494-A4140494, November 12, 2024. Background:Primary care after pregnancy is recommended, especially for individuals with recent adverse pregnancy outcomes (APOs, such as preeclampsia or gestational diabetes), who are at increased risk for future heart disease. Health-related social needs (HRSNs) are recognized barriers to care, yet their pregnancy-related prevalence and associations with care are unknown. We sought to (1) describe the pregnancy-related prevalence of HRSNs, and (2) assess associations between pregnancy-related HRSNs and subsequent linkage to primary care.Methods:We analyzed electronic health record data for individuals with prenatal care and delivery (2018-2021) at our urban safety-net hospital. HRSNs were assessed via a routine screener, and we summarized individual responses during pregnancy through 6 weeks post partum as: any positive, all negative, or never screened. Postpartum linkage to primary care was defined as a completed primary care visit after 6 weeks through 1 year post partum. We analyzed the prevalence of HRSNs and their associations with linkage to primary care, using adjusted log-linked binomial regression models. In stratified models we assessed for effect modification by APO history and other variables.Results:Of 4941 individuals in our sample, 53% identified as Black non-Hispanic and 21% as Hispanic, 68% were publicly insured, and 93% completed ≥1 HRSN screening. Nearly 1 in 4 screened positive for any HRSN, most often food insecurity (14%) or housing instability (12%), and 53% linked to primary care. Compared with those who screened negative for all HRSNs (n=3491), linkage to primary care was similar among those who screened positive for any HRSNs (n=1079; adjusted risk ratio, aRR 1.04, 95% confidence interval, CI: 0.98-1.10) and lower among those never screened (n=371; aRR 0.77, 95% CI: 0.68-0.86). We found no evidence of effect modification by APO history, race/ethnicity, insurance, language, or Covid-19 pandemic exposure.Conclusions:In this diverse postpartum sample, we identified a 24% prevalence of pregnancy-related HRSNs and 53% subsequent linkage to primary care. Linkage to primary care was not associated with HRSN screening result (positive versus negative) but was significantly negatively associated with being missed by HRSN screening. Further research is needed to better understand HRSN screening practices and who is missed by screening, and to identify modifiable barriers to postpartum primary care especially after APOs.

Circulation, Volume 150, Issue Suppl_1, Page A4135476-A4135476, November 12, 2024. Purpose:When the heart is exposed to stresses such as myocardial infarction or hypertension, it undergoes compensatory hypertrophy in response. However, continuation of the stress causes this compensatory mechanism to fail, and eventually systolic dysfunction or decompensated heart failure occur. As the hypertrophy of individual cardiomyocytes has been observed in this process, controlling cardiomyocyte hypertrophy is a potential target the prevention and treatment of heart failure. In this study, we constructed a high throughput screening (HTS) assay using cardiomyocyte hypertrophy as an index parameter. Compounds that inhibit cardiomyocyte hypertrophy were selected from our low molecular compound library.Methods and Results:In the primary screening, cultured rat primary cardiomyocytes were treated with each compound at a final concentration of 1 µM and then stimulated with 30 µM phenylephrine (PE) for 48 hours. These cells were subjected to fluorescent immunostaining with α-actinin, and cardiomyocyte area was measured using an ArrayScan™ system. The hypertrophy inhibition rate (%) of each compound was calculated as [(PE(+) – compound) / (PE(+) – PE(-))] × 100. The compounds with a hypertrophy inhibition rate greater than 50% and less than 150% were selected as hit compounds. In the secondary screening, these hit compounds were evaluated based on the dose-dependency of cardiomyocyte hypertrophy inhibition and the inhibition of the mRNA levels of the cardiac hypertrophy response genes ANF and BNP using real-time PCR. From the 269 low molecular-weight compounds in the original compound library, eight were selected through the primary and secondary screenings. Among them, we focused on Reference Number 409 (RFN-409). Western blotting indicated that RFN-409 inhibited PE-induced p38 activation. Next, we investigated the effect of RFN-409 on heart failure. Eight-week-old male C57 BL/6J mice were subjected to transverse aortic constriction (TAC) surgery and then randomly assigned to intraperitoneal treatment with RFN-409 (3, 10 mg/kg) or vehicle for eight weeks. RFN-409 at 10 mg/kg significantly prevented TAC-induced increase in left ventricular posterior wall thickness and decrease in left ventricular fractional shortening.Discussion:RFN-409 suppressed TAC-induced development of heart failure, at least partially by inhibiting p38 activity. These findings suggest that RFN-409 may be an effective agent for heart failure therapy.

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.