Risultati per: Raccomandazioni sullo screening del diabete per gli adulti

Circulation, Volume 150, Issue Suppl_1, Page A4121454-A4121454, November 12, 2024. Introduction:Recent research has shown that AI is able to assess biological aging and cardiovascular disease (CVD) risk using chest radiographs. However, the lack of explainability of such deep learning algorithms hinders clinical utility and adoption. This motivates the current study which searches for and tests the use of machine extractable quantitative features in chest radiographs to predict CVD risk in population screening.Method:Chest radiograph measurements characterizing cardiomediastinal geometry, aortic calcification and tortuosity were handpicked for development of a segmentation-based feature extraction algorithm. The algorithm was applied on the PLCO lung screening dataset for analysis. The association between measurement-based imaging features, clinical characteristics (age, sex, BMI, smoking status, hypertension, diabetes, liver disease) with CVD mortality and 10-year major adverse cardiovascular events (MACE) were analysed by using proportional hazard regression, with feature selection done by LASSO.Result:Of 29,453 eligible subjects, 5693 subjects from a single study centre were used for fitting of all models. The median follow-up time was 19 years. A total of 32 imaging features were extracted and analysed. For both 10-year MACE and CVD mortality, model using imaging features, age, and sex performed similarly to model using conventional risk factors, and a deep learning chest radiograph CVD risk model. Two imaging features, mediastinal width at valve-level [HR 1.36 (1.23-1.50)] and maximal lateral displacement of descending aorta [HR 1.29 (1.18-1.42)] were found to be prognostic. To the best of our knowledge, these features have not been reported previously.Conclusion:Quantitative imaging features can predict CVD risk in chest radiograph similar to deep learning models while providing feature interpretability and explainability. Two novel imaging features prognostic of CVD risk were found and shown to be complementary to conventional risk factors.

Circulation, Volume 150, Issue Suppl_1, Page A4146283-A4146283, November 12, 2024. Objective:The incidence of cognitive decline following coronary artery bypass grafting (CABG) is well-documented, significantly impacting patient morbidity, mortality, and quality of life. We conducted a systematic review that examines cognitive outcomes in CABG randomized controlled trials (RCTs) to identify which cognitive assessments were used, their administration frequency, attrition rates, and their effectiveness in detecting perioperative cognitive changes in control groups.Methods:We conducted a search of MEDLINE, EMBASE, Cochrane Library, and PsycINFO for CABG RCTs that included cognitive assessments, from January 2005 to December 2023. Descriptive statistics were used to summarize the frequency, domains, and attrition rates of each cognitive task. For tasks assessed both pre- and post-operatively in at least three RCTs, control group scores and standard deviations were reported.Results:Out of 3337 screened studies, 2163 were CABG RCTs, and only 69 (3.2%) included cognitive evaluations (Figure 1). These trials involved 15,839 subjects (79% male, mean age 64.4, median follow-up time 90 days) and used 145 unique cognitive tasks. The Trailmaking Test Part B (40/69; 58.0%) and Part A (38/69; 55.0%) were the most frequently used. Only 7 tasks had means and standard deviations reported before and after surgery in more than three RCTs, and none detected significant pre- to post-operative changes. Attrition rates averaged 19.3%, with a wide range from 0% to 62%. Figure 2 demonstrates the decline in cognitive assessments in CABG trials over the years, with a sharp decline after 2014. Trials that assessed cogntion after 2014 tended to favor screening tasks (MMSE/MoCA) alone.Conclusion:Cognitive assessments are infrequent in CABG trials, and existing tests fail to consistently detect cognitive changes. To effectively evaluate and address cognitive impact after CABG, new assessment strategies that are resilient to attrition and practical for use in diverse trial settings are needed.

Circulation, Volume 150, Issue Suppl_1, Page A4144973-A4144973, November 12, 2024. Background:Cardiac calcium, which includes coronary and extra-coronary calcification, is often incidentally found in chest CT scans performed for various reasons. Despite its prognostic value, manual quantification of cardiac calcium in non-gated chest CT images is labor-intensive.Goals:This retrospective study aims to perform automatic quantification and scoring of cardiac calcium in non-contrast-enhanced chest CTs. The objective is to determine associations between automatic calcium scoring and outcomes such as all-cause mortality, non-fatal myocardial infarction (MI), and non-fatal stroke.Methods:We conducted a nationwide cohort study using the Taiwan National Health Insurance Research Database (NHIRD) from 2016 to 2022. Patients under 20 years old, with a diagnosis of malignancy, or with outcome events before the CT acquisition were excluded. HeaortaNet 1.0, a validated AI model, was used for cardiac calcium scoring. Comorbidities were determined using ICD diagnostic codes for ≥2 consecutive outpatient visits within the year before the index date. Outcomes were censored at the first occurrence of mortality or relevant ICD codes for MI or stroke.Results:The retrospective cohort included 279,415 patients (56.37% male, mean age 60.31±16.54). All-cause mortality occurred in 12.82% of patients within a 3-year follow-up. The 3-year incidence rates of non-fatal MI and non-fatal stroke were 0.86% and 2.07%, respectively. Multivariate-adjusted Cox hazard ratios (95% confidence intervals) for any composite outcome were 1.51 (1.46-1.57), 2.09 (2.01-2.17), 2.63 (2.53-2.74), and 3.37 (3.24-3.50) for cardiac calcium scores of 1-100, 101-400, 401-1000, and >1000, compared to a score of 0. Adjusted Cox hazard ratios for all-cause mortality were 1.62 (1.56-1.69), 2.29 (2.19-2.39), 2.91 (2.78-3.04), and 3.80 (3.64-3.96) for scores of 1-100, 101-400, 401-1000, and >1000, compared to a score of 0.Conclusion:AI-enabled opportunistic screening of non-contrast chest CT for cardiac calcium scoring is associated with all-cause mortality and cardiovascular events. This is the first large-scale cohort study to use an AI model for comprehensive cardiac calcium screening.

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 A4144947-A4144947, November 12, 2024. Background:Right heart catheterization (RHC) is the gold standard for diagnosing heart failure with preserved ejection fraction (HFpEF). An FDA-approved artificial intelligence (AI) technology uses a four-chamber transthoracic echocardiogram (TTE) image to screen patients for HFpEF.Methods:We compared invasive hemodynamic data between patients screened for HFpEF by this TTE AI algorithm. We retrospectively collected data from two cohorts of patients with an ejection fraction (EF) ≥ 50% undergoing RHC for the evaluation of HFpEF. The most recent TTE was screened using the AI tool and reported as either suggestive or non-suggestive for HFpEF – labeled as “positive” or “negative,” respectively. Invasive hemodynamic parameters at rest and during exercise were collected. Positive and negative groups were compared using Student’s t-test and Mann-Whitney U test.Results:A total of 47 patients (82% women, 79% Black, average EF 62%) had a previous RHC, with 23 undergoing subsequent exercise RHC. There were 18 patients (38%) with a positive AI result and 29 (62%) negative. Positive patients had significantly higher rates of atrial fibrillation (38% vs 11%, p=.03), NT-proBNP levels (median 451 vs 117 ug/mL, p=.001), and H2FPEF (median 6 vs 4, p 15 mmHg, consistent with HFpEF, compared to only 14 of 28 (50%) negative patients. With exercise 6 of 7 (86%) positive patients had PCWP ≥ 25 mmHg, consistent with HFpEF, compared to 11 of 20 (55%) negative patients. At rest, positive patients had significantly higher PCWP, mean pulmonary arterial pressure (mPAP), and pulmonary vascular resistance (PVR). After exercise, there were no significant differences in PCWP or mPAP between the two groups, but thermodilution cardiac output was significantly lower in the positive patients.Conclusion:Patients identified as HFpEF positive by a validated TTE-guided AI tool were more likely to have HFpEF confirmed invasively, indicating its potential for risk stratification. However, the negative predictive value for HFpEF confirmed by invasive hemodynamics was low in this population.

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 A4145962-A4145962, November 12, 2024. Introduction:Obstructive sleep apnea (OSA) affects nearly a billion adults worldwide, and is associated with an increased risk of coronary artery disease, heart attack, heart failure, and arrhythmias – notably atrial fibrillation (AF). Low cost, point of care mobile electrocardiograms (MobileECGs) record and detect heart rhythm abnormalities in 30 seconds. This study aims to assess the effectiveness of the KardiaMobile (AliveCor) MobileECG device as an AF screen in the OSA patient population.Methods:The MobileECG Sleep Study enrolled 500 adult University of Florida Health patients in an observational study between March 2021 and March 2024. After providing consent and completing a brief survey regarding pre-existing health conditions and overall sleep health, a trained research assistant performed the AF screening with the KardiaMobile ECG device. ECG readings were marked for previously undetected abnormalities (potential AF, tachycardia, bradycardia, etc.) and statistically analyzed to determine stroke risk using the CHA2DS2-VASc scoring system. CHA2DS2-VASc criteria includes congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female).Results:A total of 500 participants were enrolled over a 3 year period at University of Florida Health Sleep Center. Of which 276 (55.2%) were female and 224 (44.8%) were male, with a mean age of 56.34 (SD 15.74) and a mean weight of 222.50 (SD 63.25). Of those tested, 68 (13.6%) had irregular, previously undetected AF readings. Patients with irregular AF readings using the KardiaMobile ECG device had CHA2DS2-VASc scores of t(68) = 2.15, p = .042, d = 0.26 indicating an intermediate risk for stroke. Oral anticoagulation is recommended for a score of ≥ 2 if the patient has no contraindication. After prior 12-lead ECG data for patients is obtained the determinations will be compared to the KardiaMobile ECG readings using Cohen’s Kappa.Conclusion:MobileECGs offer a rapid, point of care screening tool for AF in an outpatient sleep clinic setting. Early detection of AF in the OSA patient population can result in improved outcomes and reduced instances of stroke events through anticoagulation therapy guided by CHA2DS2-VASc scores. Further research is necessary to understand the long term impact of surveillance AF screening in high risk patient populations on mortality and cost of healthcare.

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 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 A4131622-A4131622, November 12, 2024. Introduction:Chronic liver disease affects more than 1.5 billion adults worldwide, but the majority of cases are asymptomatic and undiagnosed. Echocardiography is broadly performed and visualizes the liver; however, this information is not diagnostically leveraged.Hypothesis and Aims:We hypothesized that a deep-learning algorithm can detect chronic liver diseases using subcostal echocardiography images that contains hepatic tissue. To develop and evaluate a deep learning algorithm on subcostal echocardiography videos to enable opportunistic screening for chronic liver disease.Methods:We identified adult patients who received echocardiography and abdominal imaging (either abdominal ultrasound or abdominal magnetic resonance imaging) with ≤30 days between tests. A convolutional neural network pipeline was developed to predict the presence of cirrhosis or steatotic liver disease (SLD) using echocardiogram images. The model performance was evaluated in a held-out test dataset, dataset in which diagnosis was made by magnetic resonance imaging, and external dataset.Results:A total of 2,083,932 echocardiography videos (51,608 studies) from Cedars-Sinai Medical Center (CSMC) were used to develop EchoNet-Liver, an automated pipeline that identifies high quality subcostal images from echocardiogram studies and detects presence of cirrhosis or SLD. In a total of 11,419 quality-controlled subcostal videos from 4,849 patients, a chronic liver disease detection model was able to detect the presence of cirrhosis with an AUC of 0.837 (0.789 – 0.880) and SLD with an AUC of 0.799 (0.758 – 0.837). In a separate test cohort with paired abdominal MRIs, cirrhosis was detected with an AUC of 0.726 (0.659-0.790) compared to MR elastography and SLD was detected with an AUC of 0.704 (0.689-0.718). In the external test cohort of 66 patients (n = 130 videos), the model detected cirrhosis with an AUC of 0.830 (0.738 – 0.909) and SLD with an AUC of 0.768 (0.652 – 0.875).Conclusions:Deep learning assessment of clinically indicated echocardiography enables opportunistic screening of SLD and cirrhosis. Application of this algorithm may identify patients who may benefit from further diagnostic testing and treatment for hepatic disease.

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 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 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 A4143538-A4143538, November 12, 2024. Introduction:Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease that may result in heart failure (HF), arrhythmias, and valvular disease. Our aim was to develop (1) screening criteria to identify high-risk patients for ATTR-CM and (2) our own predictive tool of ATTR-CM.Methods:This was a prospective observational registry at 2 academic sites in Canada. We designed screening criteria to identify high-risk patients in HF, atrial fibrillation, transcatheter valve clinics, and in cardiologist’s offices from January 2019-December 2022. Patients >60 years were included if one of several screening criteria was met and they were referred for pyrophosphate scan by the cardiologist. Univariate and multivariate logistic regression were used to identify predictive clinical, imaging, and biochemical characteristics.Results:In total, 2500 patients were screened, and 200 patients were enrolled with a follow-up duration of 3 years. The mean age was 78 years and 65% were male. Forty-six (23%) had a diagnosis of ATTR-CM and 7 (4%) were diagnosed with AL-amyloidosis. ATTR-CM patients were older (83±7 vs. 77±8; p