Risultati per: Screening della retinopatia diabetica

Circulation, Volume 146, Issue Suppl_1, Page A10257-A10257, November 8, 2022. Introduction:Transthyretin cardiac amyloidosis (ATTR-CA) has been associated with severe aortic stenosis (AS), with some studies finding up to 20% of patients who undergo transcatheter aortic replacement (TAVR) have ATTR-CA. New therapies for ATTR-CA have brought significant interest in identifying patients at high risk for this disease. The purpose of this study was to prospectively evaluate the yield of universal testing for ATTR-CA in older patients with severe AS.Methods:All patients ≥ 70 years with severe, native, and degenerative AS seen in valve clinic for evaluation of TAVR were referred for technetium-99m pyrophosphate cardiac scintigraphy (PYP scan). Diagnosis was made via a combination of planar grade, heart to contralateral lung ratio, and single positron emission computed tomography/computed tomography. Patients with a positive PYP scan were referred for appropriate laboratory testing to rule out AL amyloidosis. Clinical and echocardiographic factors were correlated with the PYP result.Results:Over a 12-month period, 787 patients with severe AS were screened of which 543 met the inclusion criteria. Of these patients, 298 underwent a PYP scan with 232 not undergoing the scan for logistical and scheduling issues during the pandemic. The positivity rate was 4.3% (13/298). Patients with a positive PYP scan had higher rates of carpal tunnel syndrome (54% vs 14%, p -18%) (100% vs 69%, p=0.044), low stroke volume index (≤35 ml/m2) (92% vs 42%, p

Circulation, Volume 146, Issue Suppl_1, Page A15026-A15026, November 8, 2022. Introduction:A novel technology utilizing artificial intelligence (AI) to provide real-time image-acquisition guidance, enabling novices to obtain diagnostic echocardiographic (echo) images holds promise to expand the reach of echo screening for rheumatic heart disease (RHD). We evaluated the ability of non-experts to obtain diagnostic quality images in patients with RHD using AI guidance (Caption Health) with color Doppler.Methods:This study was performed in Kampala, Uganda at the Uganda Heart Institute. Nurses and nursing students with no prior echo experience underwent one-day training in the use of AI guidance, which included a 7-view screening protocol with 2D and color Doppler images. Following training, all participants scanned 8-10 patients using AI guidance, half RHD and half normal. The same patients were scanned by two expert sonographers without the use of AI guidance. Each echo was evaluated by a panel of 4 expert echocardiographers blinded to the identity of the scanner (novice/exert) and diagnosis of the patient to provide quality assessment including (1) diagnostic quality to determine presence/absence of RHD, (2) more detailed valvular assessment, and (3) ACEP score 1-5 for each view.Results:Thirty-six novice scanners scanned a total of 50 patients, 25 with RHD and 25 controls. A total of 462 echocardiogram studies were obtained, 351 obtained by non-experts using AI guidance and 111 obtained by expert sonographers without AI guidance. Preliminary analysis of 394 interpretations showed that 95% of non-expert studies were of diagnostic quality to assess for RHD and mitral valve disease (vs 100% by experts, p=0.03), but only 56% of non-expert studies were of diagnostic quality to assess aortic valve disease (vs 97% by experts, p

Circulation, Volume 146, Issue Suppl_1, Page A14675-A14675, November 8, 2022. Introduction:Genome-wide association studies (GWAS) have discovered >300 associations for CAD. Few loci are functionally characterized and may represent new mechanisms of disease.Hypothesis:Can a high-throughput, unbiased transcriptional screen for all candidate GWAS genes identify the causal genes and biological pathways at CAD GWAS loci in endothelial cells (ECs)?Methods:We applied CRISPRi-Perturb-seq to knock down the expression of all genes within 500 Kb of coronary artery disease GWAS loci (2,300 genes in total) and measure their effects on the transcriptome using single-cell RNA-seq.Results:We identified 60 programs of co-expressed genes, which represent core cellular pathways (i.e. ribosome biogenesis) and EC-specific pathways such as flow response and angiogenesis. The EC-specific programs show the greatest contribution to CAD heritability. 6 EC-specific programs have the greatest number of CAD GWAS candidate genes. One of the EC-specific programs had genes regulated byKLF-transcription factors and was enriched for shear-stress response genes. The novel CAD candidate genes in this program included multiple known mediators of the cerebral cavernous malformation (CCM)-signaling complex. 9 known members of the CCM-signaling cascade and several potentially novel mediators of CAD clustered together in theKLFPerturb-seq topic. These included genetic variants in theCCM2,KLF4,RAC1, andHEG1loci as well as genes will a similar transcriptional profile but no prior connection to the CCM-signaling complex.Conclusions:High-throughput functional analysis of 2,300 genes proximal to CAD GWAS loci prioritized pathways—such as angiogenesis and EC migration—that are regulated by multiple risk SNPs. Our study identifies new genes that likely influence risk for CAD, identifies convergence of CAD genes into certain pathways in endothelial cells, and demonstrates a generalizable strategy to connect disease variants to functions.

Circulation, Volume 146, Issue Suppl_1, Page A13225-A13225, November 8, 2022. Introduction:Frailty is a major risk factor for adverse health events in older adults with cardiovascular disease.Hypothesis:We sought to develop and validate a predictive model leveraging data available in the electronic health record to screen for frailty as defined by a prospective reference standard.Methods:We conducted a population-based cohort study using data from the Canadian Longitudinal Study of Aging (CLSA). From 2010-2015, the CLSA enlisted a diverse and multi-ethnic sample of community-dwelling adults 45-85 years of age. Comprehensive phenotyping was performed through interviews at participants’ homes and assessments at data collection sites. Frailty was quantified by the 47-item Frailty Index (FI) Examination, consisting of tests for age-related deficits in physical performance, body composition, cardiovascular and pulmonary physiology, cognitive and sensory function. After dividing our sample into training (80%) and test (20%) sets, we compared machine learning and linear regression models to predict the FI based on age, sex, comorbidities, and blood test results. We used the H2O AutoML platform (DAI 1.10.2) to iteratively determine the optimal model.Results:The cohort consisted of 30,097 adults with a mean age of 63±10 years and 51% females. The mean FI score was 0.28±0.08 (best-worst 0.07-0.70). The gradient-boosted machine learning model achieved an R2of 0.512 and a root mean squared error (RMSE) of 0.058 to regress FI scores, and an area under the curve of 0.766 to classify FI quintiles, selecting the following 10 variables in descending order of importance: age, chronic heart failure, hypertension, glycated hemoglobin, high-sensitivity C-reactive protein, high-density lipoprotein, red cell distribution width, vitamin D, female sex, and diabetes. The linear regression model achieved a similar R2and RMSE with all 62 input variables and a modest decline after selecting the top 10 input variables using a leaps-and-bounds algorithm.Conclusions:Frailty screening can be performed at scale for clinical or research purposes using common clinical and biochemical inputs. Our machine learning model predicted frailty with a manageable number of inputs and yielded pathophysiological insights about their relative importance.

Circulation, Volume 146, Issue Suppl_1, Page A9447-A9447, November 8, 2022. Introduction:Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients aged > 60 years. While the V122I variant that is associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the US (or 1.5 million people), the phenotypic penetrance of this allele remains incompletely defined owing to age-dependent expression and limited methods for disease ascertainment.Methods:The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study is a currently accruing multisite cohort designed to determine the prevalence of ATTR-CM using Tc-99m-Pyrophosphate imaging in older (age > 60 years) Black and Hispanic individuals with HF.TTRgenotype is determined by 4-exon targeted PCR, while functional, biochemical, and echocardiographic testing is performed. Data are presented here as an interim analysis performed using Kruskal-Wallis testing for the first 240 self-identified Black participants.Results:The prevalence of V122I was 6.7% (n=16 carriers of whom 7 had ATTR-CM), yielding a phenotypic penetrance of 44% (95% CI 20%, 70%) at a median age of 82 (IQR 74, 85) years. Allele carriers with ATTR-CM (Group 3) were older and more likely male, with lower 6-minute walk distance and LVEF, when compared to carriers without ATTR-CM (Group 2, Table) or wild-type, non-amyloid HF controls (Group 1). Other functional, biochemical, and echocardiographic parameters were predictably different between Group 3 and the other groups but similar between Groups 1 and 2 except for prealbumin levels (Group 1: 25 mg/dl vs. Group 2: 20.5 mg/dl, p < 0.05).Conclusion:The clinical penetrance of V122I among elderly Black individuals with HF and a median age of 82 years was 44%, suggesting that genotype alone is insufficient to infer ATTR-CM as the cause of HF in this clinical context. Prealbumin concentration may be useful to identify ATTR-CM in V122I carriers.

Circulation, Volume 146, Issue Suppl_1, Page A12279-A12279, November 8, 2022. Introduction:Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-c) and very high risk of premature atherosclerotic cardiovascular (ASCVD) and aortic/supraortic valve heart diseases (VHD). The study aim was to examine clinical and biochemical trajectories of a cohort of HoFH patients since childhood.Methods:In this longitudinal study we assessed the incidence of manifest or subclinical ASCVD (coronary or carotid) and VHD as well as plasma lipids in a cohort of HoFH subjects during a 12.9 ± 9.6 years follow-up.Results:From the 868 individuals ≤19 y-old (at baseline) that were genotyped on a genetic cascade screening program, 420 (48.4%) had an FH mutation. From children bearing mutations, 12 were true homozygotes and 1 was compound heterozygote (53.8% females, mean age 7.5 ± 4.1 years at the first visit). During follow-up all were on statin and ezetimibe therapies, and the mean final dose of atorvastatin was 56 ± 27 mg/d (n=10); and rosuvastatin, 26 ± 17 mg/d (n=3). Initial and on treatment LDL-c were 655 ± 177 mg/dL and 399 ± 150 mg/dL, respectively, with a mean 39.1% reduction (-256 mg/dL). None were under LDL apheresis; 2 patients used mipomersen, 2 lomitapide, and 2 are currently using PCSK9 inhibitors. Subclinical cardiovascular disease, either coronary, carotid or in aortic valve, was identified in 38.5% (n=5; mean age 16.4 ± 9.8 years), whereas 30.8% had a clinical cardiovascular event (n=4; mean age 22.8 ± 6.8 years), with 2 deaths. Therefore, 69.3% had either subclinical or manifest cardiovascular disease.Conclusion:Despite early diagnosis and LDL-c reduction HoFH is still marked by an adverse and premature cardiovascular disease progression. Conventional lipid lowering therapies are not adequate to prevent ASCVD and VHD disease course.

Circulation, Volume 146, Issue Suppl_1, Page A10856-A10856, November 8, 2022. Introduction:Prior AF screening trials demonstrated low yield, highlighting the need for more targeted approaches. An AI algorithm was developed to identify ECG signatures of AF risk during normal sinus rhythm, which has been validated in diverse external populations.Hypothesis:An AI-guided, targeted screening approach could improve the diagnosis of AF.MethodsWe conducted a pragmatic decentralized trial to prospectively recruit patients with stroke risk factors but no prior AF. The AI algorithm was applied to the ECGs performed in routine practice and divided patients into high- or low-risk groups. The primary endpoint was AF lasting ≥ 30 seconds on a subsequent 30-day continuous cardiac rhythm monitor. In a secondary analysis, trial participants were 1:1 propensity score-matched to real-world controls derived from the eligible but unenrolled population.ResultsA total of 1,003 patients from 40 U.S. states completed the study, with a mean age of 74 [SD 8.8] years. Over a mean of 22.3 days of continuous monitoring, AF was detected in 6 (1.6%) of low-risk patients and 48 (7.6%) of high-risk patients (OR 4.98 [2.11-11.75], p

Circulation, Volume 146, Issue Suppl_1, Page A13817-A13817, November 8, 2022. Previous studies from India reported management of diabetes (diagnosed: 53%, treated: 41%) among adults 15-49 years, a fraction of those suffering from disease. This study aimed to provide nationally-representative estimates of (i) the proportion of all adults (18+ years) with prediabetes and diabetes mellitus (DM), and (ii) the heterogeneity in their cascade of care by natal sex, age, and urbanicity.Methods:Using data from non-pregnant women (n = 959,468) and men (n = 935,829) in the National Family Health Survey-V (2019-21), we estimated the sex-specific prevalence of prediabetes and DM (see footnotes ofFigure), and among adults with diabetes, the self-reported care cascade (ever screened, diagnosed, taking medication, under control defined by normoglycemia). All estimates incorporated the complex survey design and were stratified by urban versus rural or by age group (18-39, 40-64, 65+).Results:Nationally, the prevalence of prediabetes and DM were 11.3% (95%CI: 11.1,11.4) and 6.5% (95%CI: 6.4, 6.6) respectively. Prediabetes was similar in urban areas (vs rural areas) among men (%; 12.9 vs 12.0) and women (%; 11.1 vs 10.1). DM was higher in urban areas (vs rural areas) among men (%; 8.8 vs 5.6) and women (9.0 vs 5.3). Both prediabetes and DM were higher with increasing age. Screening in the total population was 30%, and was higher in urban areas, among women and higher with age. Among those with DM, only 72%, 51%, and 29% reported being diagnosed, taking medication, and under control, respectively. Diagnosis, treatment and control were also higher in urban areas, women, and older age groups (Figure).Conclusions:Despite the high prevalence of diabetes, there is a high unmet need in screening, diagnosis, treatment and control of disease nationally, and this is pronounced in rural adults. Moreover, the prevalence of prediabetes is high in rural areas, and those under 40 years, requiring a comprehensive approach for prevention and management.

Circulation, Volume 146, Issue Suppl_1, Page A14935-A14935, November 8, 2022. Introduction:The electrocardiogram (ECG) contains information about age-related changes in cardiovascular physiology, which have been linked with the frailty syndrome.Hypothesis:We sought to develop and validate a predictive model leveraging the 12-lead ECG to screen for frailty as defined by a prospective reference standard.Methods:We conducted a population-based cohort study using data from the Canadian Longitudinal Study of Aging (CLSA). From 2010-2015, the CLSA enlisted a diverse and multi-ethnic sample of community-dwelling adults 45-85 years of age. Comprehensive phenotyping was performed through interviews at participants’ homes and assessments at data collection sites. Frailty was quantified by the 110-item Frailty Index (FI) Composite, consisting of self-reported comorbidities, blood tests, physical performance tests, body composition tests, cardiovascular and pulmonary tests, cognitive and sensory tests. After dividing our sample into training (80%) and test (20%) sets, we developed an end-to-end deep neural network to predict the FI score based on the 12-lead ECG time series.Results:A total of 26,700 ECGs with paired FI scores were evaluated. For classification of FI quintiles, a bidirectional long short-term memory (BiLSTM) neural network with a cross-entropy loss function achieved a 5-fold mean area under the receiver operating characteristics curve (AUROC) of 0.70 and area under the precision-recall curve (AUPRC) of 0.36. Predictive performance was superior for classification of the first (most robust) quintile that had AUROC 0.79 and AUPRC 0.46, and the fifth (most frail) quintile that had AUROC 0.79 and AUPRC 0.56, as compared to the middle quintiles that had AUROC 0.60-0.69 and AUPRC 0.27-0.29.Conclusions:Our deep learning model can be used to screen for high or low levels of frailty based on the readily available 12-lead ECG. Additional research is underway to gain insights into other representations of the ECG signal and relative importance of the ECG features.

Circulation, Volume 146, Issue Suppl_1, Page A11199-A11199, November 8, 2022. Introduction:Postpartum depression (PPD) affects 1 in 5 women in the United States and is associated with cardiovascular disease. Disparities in PPD screening have not been well studied. We investigated the level of self-reported screening, diagnosis of PPD, and disparities in screening.Methods:We utilized data from participants enrolled in the AHA Research Goes Red Registry, an online research platform powered by Verily, who responded to the Fertility and Pregnancy survey. Of the 3128 women who had responded as of May 2022, 311 participants were self-identified as postpartum women and were included in this analysis. The definition of postpartum in the survey was“I have been pregnant within the last 12 months”. The survey included questions on PPD screening and diagnosis. We used chi-squared testing to examine differences by race-ethnicity, education, income, and proximity to healthcare in PPD screening.Results:Among the 311 postpartum women (mean age: 33.3 ± 4.8 years), 83% recalled being screened for PPD. Of the 311 women, 15% reported a diagnosis of PPD, of which 92% received treatment. There were no significant differences in PPD screening by race-ethnicity: non-Hispanic White (82%), non-Hispanic Black (83%), Asian (88%), Hispanic (80%) (p=0.91), possibly limited by sample size (Fig 1a). Similarly, there were no significant differences by educational status (p=0.22) (Fig 1b) or income (p=0.53) (Fig 1c). Women who lived in a big city with access to many hospitals had higher proportion of screening (88%), while rural area dwellers had the least (74%, p=0.54) (Fig 1d).Conclusion:Among this multiracial cohort of postpartum women, the prevalence of self-reported screening and diagnosis of PPD was 83% and 15%, respectively. The prevalence of screening did not significantly differ by race-ethnicity, education, income, and proximity to healthcare. Future larger studies were suggested to explore screening of PPD by race and other social determinants of health.

Circulation, Volume 146, Issue Suppl_1, Page A13601-A13601, November 8, 2022. Introduction:Truncating variants inTTN(TTNtvs) are the largest genetic cause of dilated cardiomyopathies (DCM). In populations, genetic variation inTTNis pervasive and penetrance estimates for DCM are low, even when carriers are limited to those withTTNtvs in exons with “percentage spliced in” index > 90 (hiPSI), a representation of constitutive cardiac expression. Patients with cardiomyopathies (CM) often carry a large number of other cardiac conditions, such as atrial fibrillation (Afib). We sought to confirm this association and determine whether the presence of Afib and a hiPSITTNtv predicted CM.Results:Leveraging clinicogenomic data from ~450,000 individuals in two health systems, we show support for associations with both CM and Afib at the population level. We perform a sliding window analysis ofTTNtvs and confirm the association is specific to hiPSI exons, with no meaningful associations in exons with less cardio expression. The combination of hiPSITTNtv carrier status and early Afib diagnosis (dx before age 60) finds a subset ofTTNcarriers at high risk for CM (34% prevalence) – this risk is 3.5 fold higher than that of all hiPSITTNtv carriers (9% prevalence) and 5-fold higher than non-carriers with early Afib (5% prevalence, p=4.8e-56 after controlling for age and sex). Further, Afib either predates or is concurrently diagnosed with CM in 72% of those with both diagnoses.Conclusion:CM and Afib are linked in hiPSITTNtv carriers and may represent progressive manifestations of structurally-based heart failure. Our retrospective analysis suggests hiPSITTNtv screening (~0.5% of cohorts) in conjunction with routine monitoring for arrhythmias may be an effective strategy to improve outcomes and reduce the incidence of severe cardio outcomes in the population.

Circulation, Volume 146, Issue Suppl_1, Page A14324-A14324, November 8, 2022. Introduction:Untreated obstructive sleep apnea (OSA) is a major cause of uncontrolled atrial fibrillation (AF). It represents a high prevalence and incidence, as well as significant cause of mortality. Uncontrolled AF with recurrent emergency department (ED) visits and inpatient admissions poses a burden to patient quality of life and increased risk of cardiovascular events, in addition to healthcare costs.Hypothesis:We aim to reduce ED visits and hospitalizations for General Internal Medicine resident clinic patients with OSA and uncontrolled AF over the next year by 10%.Methods:We identified approximately 382 patients with inclusion criteria of age 18-70 years with a history of both AF and OSA without documented CPAP use. Interventions included a week long educational session to all residents starting March 2022, standardizing CPAP device ordering/monitoring, and patient education. A protocol for sleep study ordering and CPAP titration was implemented across clinics. The next phase is inpatient screening and referrals.Results:Prior to our intervention date, 14.7% of our study population presented with uncontrolled AF in the past year. Since our interventions, 2.4% have presented with uncontrolled AF.Conclusions:Our preliminary interventions have shown a numerical trend towards decreasing rates of uncontrolled AF in patients with OSA at our institution. Our interventions are ongoing with periodic evaluation of outcomes. Our findings support the need for a comprehensive approach targeting both providers and patients.

Circulation, Volume 146, Issue Suppl_1, Page A11937-A11937, November 8, 2022. Introduction:Isolated cardiac sarcoidosis (ICS) poses a diagnostic challenge due to its patchy myocardial involvement and low yield of endomyocardial biopsy (EMB). The diagnosis is often suggested by (18)F-fluorodeoxyglucose (FDG) avidity on positron emission tomograpy (PET) scan. Genetic cardiomyopathies (some of which may be FDG-avid) often present with similar clinical manifestations as ICS, so we evaluated a systematic screening strategy in which all patients with suspected ICS were offered genetic testing.Methods:We reviewed all patients in our Multi-Disciplinary Sarcoid Consortium for those given a diagnosis of ICS by the referring provider based on FDG-PET scans with myocardial but no systemic FDG avidity. These patients were offered genetic testing with commercially available genetic cardiomyopathy and arrhythmia panels (168 genes).Results:Of 110 patients referred, 16 met inclusion criteria, 1 had EMB-proven ICS, 1 did not consent, and 14 were referred for genetic testing. Ten patients (71%) also underwent cardiac MRI, of which 9 had late gadolinium enhancement. Mean age was 61.7±11.6 years, 12 (86%) were male. Mean ejection fraction at time of presentation was 43±10%. Four patients (29%) had presented with atrio-ventricular block, 12 (86%) with ventricular arrhythmias and 12 (86%) with left ventricular systolic dysfunction. Eight (57%) had EMB without granulomas (6 had not undergone EMB). Of these 14 patients, 5 (36%) had pathogenic mutations: 2 inLMNA,2 inTPM1,and 1 inMYBPC3. All 5 patients’ clinical phenotype was consistent with their genotype and 3 had previously been immunosuppressed without clinical improvement or resolution of FDG avidity.Conclusions:Genetic cardiomyopathy is often misdiagnosed as “isolated cardiac sarcoid.” A screening strategy of genetic testing all patients with isolated myocardial FDG avidity on FDG-PET scans had a 36% yield for pathogenic mutations and should be considered as part of routine clinical care.

Circulation, Volume 146, Issue Suppl_1, Page A14221-A14221, November 8, 2022. Introduction:Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Novel therapies for transthyretin (TTR) CA elevate the need for early identification when treatment has the greatest efficacy. The TTR CA score (TCAS) was recently developed to predict the likelihood of TTR CA in patients undergoing 99mTc-pyrophosphate scintigraphy (PYP) scanning. Its simple inputs could be easily extracted from the electronic health record (EHR), suggesting possible use as a quick, EHR-based screening tool. We perform the first external validation of the TCAS using only EHR-extracted data. We hypothesized that a screening algorithm like TCAS could be generalizable and feasible to implement using our EHR.Methods:EHR data were extracted on all patients at a large academic medical center who underwent PYP scans between 2017 and 2022. PYP scan was considered positive if the patient was part of our institution’s registry of patients with confirmed CA. Inputs – age, sex, echocardiogram wall thickness and ejection fraction, and hypertension diagnosis codes – were converted to TCAS scores. Area under the receiver operating characteristic curve (AUROC) was calculated to analyze predictive performance. Using a TCAS ≥6 as the threshold for high-risk, performance characteristics were calculated.Results:Of 365 patients who underwent PYP scan, 335 had sufficient records to calculate a TCAS. Of these 335 patients, 69 (20.6%) had positive PYP scans. Median TCAS was 5 (interquartile range 4,7). The AUROC was 0.826, with a sensitivity of 87.0%, specificity of 63.9%, positive predictive value of 38.5%, and negative predictive value (NPV) of 95.0%.Conclusions:External validation of the TCAS supports its strong predictive performance with comparable AUROCs to the initial study (0.84-0.89). Clinically, with its high NPV, the TCAS has potential to serve as a simple, low-cost screen to avoid costly PYP scans. We demonstrate the ability to extract all inputs from the EHR, without need for manual chart review or calculation, suggesting that the TCAS could function as an EHR-based screening tool. Low-cost screening tools are needed to identify patients who would benefit from TTR CA workup with PYP scanning, facilitating treatment at earlier disease stages.

Circulation, Volume 146, Issue Suppl_1, Page A9822-A9822, November 8, 2022. Background:Data mining of electronic health records (EHR) has been used as a strategy to identify patients with undiagnosed familial hypercholesterolemia (FH). Most studies have been limited by the absence of both phenotypic and genotypic data in the same cohort.Methods:Using a subset of the Geisinger MyCode Community Health Initiative (MyCode) cohort with both exome sequencing and EHR data (n=130,257), we ran two FH screening algorithms to determine genetic and phenotypic diagnostic yields: the Mayo Clinic algorithm (Mayo), which identifies those with LDL-C levels >190 mg/dL, and FIND FH®, the Family Heart Foundation’s machine learning model, to identify individuals with phenotypes suggestive of FH. With 29,243 excluded by Mayo (for secondary causes of hypercholesterolemia, no lipid value in EHR), 52,034 excluded by FIND-FH (insufficient data to run the model), and 187 excluded for prior FH diagnosis, a final cohort of 59,729 participants screened by both algorithms was created. Genetic diagnosis was based on the presence of a pathogenic or likely pathogenic (P/LP) variant in 3 genes implicated in FH via genomic screening. Charts from 180 variant negative participants (60 controls; 120 identified by FIND FH and/or Mayo) were reviewed to calculate Dutch Lipid Clinic Network scores; a score >5 defined probable or definite FH.Results:Mayo flagged 10,415 subjects; 164 (1.6%) had an FH P/LP variant. FIND-FH flagged 573; 28 (4.9%) had an FH P/LP variant giving a net yield from both algorithms of 167/240 (70%). Confirmation of a phenotypic diagnosis was constrained by lack of EHR data on physical findings or family history (high cholesterol, premature atherosclerotic disease) required for score calculation. Phenotypic FH by chart review was present by Mayo and/or FIND-FH in 13/120 vs 2/60 not flagged by either (p< 0.09).Conclusion:After excluding those with a prior FH diagnosis, applying two recognized phenotypic FH screening algorithms to the eligible MyCode cohort identified 70% of those with a P/LP FH variant. Limitations to this approach include participant exclusions for each algorithm, a low yield of positive genomic screening for Mayo, and a low yield of participants for FIND FH. Phenotypic diagnosis was rarely achievable due to missing data.

Circulation, Volume 146, Issue Suppl_1, Page A12318-A12318, November 8, 2022. Introduction:Pre-eclampsia (Pec) and gestational hypertension (GHT) are potential explanations for the female preponderance of heart failure with preserved ejection fraction. How and when to use this information clinically is unclear.Hypothesis:We hypothesized that subclinical disturbances of left ventricular (LV) structure and function (stage B heart failure, SBHF) are more common at 5-10 years post-partum in women with a history of Pec compared with women with GHT or uneventful pregnancies.Methods:The proportion of SBHF were compared between 25 women with Pec, 16 with GHT or normal pregnancy. Sub-group analysis comparing patients with and without hypertension at follow-up were also conducted.Results:Among 41 participants (age 40±6 years), followed at 9 years, SBHF was reported in 35% participants with Pec and 53% with GHT (p=0.32). Diastolic blood pressure was significantly higher in patients with SBHF than without (94±21 vs. 81±13 mmHg, p=0.035), and a similar trend was observed with systolic blood pressure (147±42 vs. 128±22mmHg, p=0.099). SBHF was observed in 6 (55%) of 11 pts with hypertension at follow-up, but only in 7 (32%) of 22 without (p=0.27). Mean LV end-diastolic volume (117.2±19.1 vs. 93.3±13.1mL,p=0.03), LV end-systolic volume (51.9±7.5 vs. 42±7 mL,p=0.04), LV mass index (73±8.6 vs. 67.3±14.6mmHg, p=0.41), E/e’ (Sept: 9.7±2.7 vs. 7.5±1.7,p=0.009; Lat: 7.4±2.6 vs. 5.5±1.7,p=0.02) were higher in participants with hypertension than without.Conclusions:9 years after pregnancy, SBHF was prevalent in pts with both previous Pec and GHT, but was not significantly different between the entities. Echocardiographic screening may add little to blood pressure follow-up in the identification of HF risk.