tbuckley/cabot-search huggingface dataset:
Abstract 14858: Revascularization Shows Beneficial Cardiovascular Outcomes in Severe Ischemic Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Shumail Fatima, Abu Hurera, Midori Torpoco Rivera, Ahmet Sezer, Gavin W Hickey
Journal: Circulation (2023)

Introduction: Revascularization approach is historically prioritized over optimal medical therapy (OMT) for patients with severe stable ischemic cardiomyopathy (ICM) with ejection fraction &lt; 35%. However, with advancement in OMT, recent studies have shown similar cardiovascular outcomes between the two strategies. Herein, we present a systematic review and meta-analysis examining the cardiovascular outcomes of revascularization strategies compared to OMT. Research Question: Is revascularization associated with improved cardiovascular outcomes in patients with severe stable ICM compared to OMT alone? Methods: PubMed, Embase, Cochrane, CT.gov, ICTRP were searched using the search terms “coronary artery bypass grafting (CABG)” or “percutaneous coronary intervention (PCI)” versus “OMT” and “ICM” or “heart failure (HF)” from inception till May 2023. Included studies compared all-cause mortality, cardiovascular mortality, HF-related deaths, acute myocardial infarction (AMI), stroke and HF hospitalization. Data were pooled into risk ratios (RR) using fixed-effects model. Results: 3 studies (n= 2050, Revascularization = 1026 and OMT= 1024) met our inclusion criteria. The follow-up period ranged from 3.4-9.8 years. Revascularization strategies primarily through CABG had protective effects for all-cause mortality (RR 0.91, 95% CI 0.84-0.98, p= 0.01, I2 0%, N= 3 studies), cardiovascular death (RR 0.83, 95% CI 0.74-0.93, p=0.00, I2 0%, N= 2 studies) and HF hospitalizations (RR 0.80, 95% CI 0.69-0.93, p= 0.00, I2 19.20%, N= 2 studies). No significant differences were observed in risks of HF related deaths, AMI and stroke between the two strategies. Conclusions: Revascularization primarily through CABG reduces all-cause and cardiovascular mortality as well as HF hospitalizations in severe stable ICM. Further studies are warranted to determine which patients can derive the greatest advantages from revascularization.
Abstract 16118: Vitamin D3 Significantly Decreases Vascular Stiffness, Improving Cognitive Impairment and Sarcopenia in a Frail, Elderly Population From Buenos Aires, Argentina
Authors: Mariano Duarte, Ignacio Davolos, Analia Aquieri, Javier Coyle, Adela Allevato, Maria A. Litta, Maria Clara Delucchi, Marcela Lecouna, Ciantia Giacobone, Eleonora Savio Galimberti
Journal: Circulation (2023)

Introduction: Aging is the leading risk factor for multiple chronic diseases especially cardio and cerebrovascular and for a decline in physical and mental function. Progressive stiffening arterial wall, cognitive impairment and sarcopenia are hallmarks of aging. Due to the pleiotropic actions that have been discovered in vitamin D (VD), which include vascular ,muscular and cognitive effects, we hypothesized that VD3 supplementation might decrease vascular stiffness and could have beneficial effect on mental status and sarcopenia in a frailty elderly population. Methods: We randomized 42 residents (78±6.5 yo; 24 females) from a public geriatric institution, to receive either 100,000 IU of VD3 or placebo (P) every 15 days for 6 months. Arterial stiffness (AS) was evaluated through central systolic pressure (cSYS), central pulse pressure (cPP), and the augmentation index (AIx) a measure of systemic AS derived from the ascending aortic pressure waveform; using Uscom® device. Cognitive function was evaluated using the Clock-Drawing Test (CDT), which is simple and effective for this population. Skeletal muscle strength/sarcopenia, were assess with the up and go test (UGT), muscle strength with hydraulic dynamometer, body mass index (BMI) and mini-nutritional assessment (MNA) test. Results: VD group showed a statistically significant decrease in AS vs P. VD Δ cSYS -12.3 mmHg, Δ cPP -6.7 mmHg mmHg and Δ AIx -17.8 %, for all three parameters: p&lt;0.05. The CDT score improved in VD group (4.3 to 5.9, p &lt;0.05) but there were no statistically significant differences in P group. Muscle strength in VD group improved significantly (from 15.1±9.4 to 18.7±3.8 Kg force/cm 2 , p&lt;0.05) vs no difference in P group. UGT improved with statistical significance in both VD and P group. The BMI and the MNA test were also favorable for VD group although they did not reach statistical significance. Conclusions: Vitamin D3 6-months supplementation improved vascular compliance by decreasing arterial stiffness, improved cognitive performance and sarcopenia indicators in this frail elderly people. Although this was a preliminary study, a larger number of patients studies should be conducted to validated these findings and to consider VD3 supplementation in this population.
Abstract 18928: Phenotypic Manifestations of Polygenic Risk for Ischemic Stroke in Adults Free From Disease
Authors: Jacob L Barber, Prashant Rao, Michael Y Mi, Usman A Tahir, Prasun K Dev, Claude Bouchard, Clary B Clish, Jeremy M Robbins, Mark A Sarzynski, Robert E Gerszten
Journal: Circulation (2023)

Introduction: Ischemic stroke is a complex heritable disease with a substantial proportion of risk attributable to polygenic factors. Little is known about how polygenic risk for stroke may manifest as intermediate phenotypes. Hypothesis: Polygenic liability for ischemic stroke will be associated with cardiometabolic phenotypes even in young adults free from disease. Methods: Polygenic risk derived from a multi ancestry population (GIGASTROKE ~1.2 million SNPs) was applied to 454 White adults from the HERITAGE Family Study with imputed whole genome data available. Participants (mean age = 31.5 ±14.5 years, 51% female) underwent robust cardiometabolic profiling including deeply phenotyped cardiopulmonary exercise tests, body composition, lipid panels, inflammatory markers, and measures of glucose homeostasis. General linear models adjusted for age and sex were used to test the association between z-scored polygenic risk of stroke (SPRS) and 130 phenotypes. A false discovery rate of &lt;5% was used to determine significance. Results: SPRS did not associate with demographic traits or measures of body composition. SPRS was positively associated with several blood pressure related phenotypes with the strongest association between SPRS and systolic blood pressure response to acute exercise (β=0.01, p=2.86e-05), which persisted after adjustment for resting systolic blood pressure. Additionally, 19 total phenotypes were nominally associated (p&lt;0.05) with SPRS including multiple apoB related plasma lipid traits ( Table 1 ). Interestingly, SPRS was also inversely associated with hematocrit (β= -0.06, FDR=0.004). Conclusions: Genetic risk of ischemic stroke is associated with hemodynamic traits even in a cohort of relatively young adults free from overt cardiometabolic disease. Additionally, blood pressure response to acute exercise may represent an early manifestation of genetic liability to stroke.
Abstract 13493: Autoimmune Myopericarditis: A Rare Presentation of Acute Myeloid Leukemia
Authors: Farrah Gaston, Amitoj Sachdeva, Dario Manley-Casco, Anwaruddin Syed, Harshavardhan Ghadiam
Journal: Circulation (2023)

Description of Case: A 51-year-old female with a past medical history of hypertension and type II diabetes mellitus presented with chest pain for 2 days that improved with sitting up and leaning forward. This was associated with exertional dyspnea and dizziness. EKG showed diffuse ST-T elevations with PR depression. The patient had a WBC Count of 1.37 X 10 9 /L, Troponin (normal 0.028 ng/ml) was 1.466&gt;1.539&gt;1.105&gt;1.105, CRP 27.35 mg/ml, ESR was 77 mm/h. The patient’s symptoms were concerning for acute pericarditis versus acute coronary syndrome. Echocardiogram showed no regional wall motion abnormality and a small pericardial effusion. Cardiac magnetic resonance imaging demonstrated myopericarditis. The infectious workup was negative. Further workup showed positive antinuclear antibody and positive smooth muscle antibody/ribonucleoprotein. Flow cytometry indicated 1% blast with immunophenotypic atypia and neutropenia. Bone marrow aspiration and biopsy confirmed 6-7% myeloblast and pathology revealed high-grade myeloid neoplasm transforming into acute myeloid leukemia (AML). The patient was initiated on ibuprofen and colchicine for myopericarditis and is currently undergoing chemotherapy. Discussion: The etiology of pericarditis includes infection, malignancy, autoimmune disease, myocardial infarction, and cardiac surgery. In one study involving 784 patients, the etiology of pericarditis was only identified among 17% of cases, with 5% of those being autoimmune and 5% of those being neoplastic. Our patient had a rare presentation of AML and this case serves as a reminder to clinicians about the importance of thorough investigation when patients present with pericarditis without a clear attributable cause to identify an underlying disease and prevent treatment delay.
Abstract 18651: Case Report: Transcatheter Edge-to-Edge Repair in a 59-Year-Old Patient With Mitral Regurgitation and Challenging Anatomy
Authors: Fathima Shafra Mubarak, Henry Seligman, Mohammed Majid Akhtar, Alison Duncan, Ali Vazir, Lauren Connolly, Katherine Good, George Asimakopoulos, Ee Ling Heng, Robert D Smith
Journal: Circulation (2023)

Re-intervention for patients with mitral valve disease is a growing challenge. We present a 59-year-old male with a history of a congenitally bicuspid aortic valve. He had valve and root replacement for aortic regurgitation in his 30s and two subsequent sternotomies for prosthesis failure and endocarditis. After admission with acute pulmonary edema, there was persistent NYHA class II-III dyspnea. Echo showed severe (grade IV) mitral regurgitation due to the dehiscence of a 32mm mitral annuloplasty ring. The coaptation point of the leaflets was posterior to the posterior aspect of the ring. No regurgitation was observed through the ring’s central orifice, but the tissue was seen on its posterior aspect, suggesting torn posterior leaflet or healed vegetation. The left ventricle was mildly dilated, and the LVEF was 53%. The right ventricle was moderately dilated with severe functional tricuspid regurgitation with a normally functioning aortic valve prosthesis. After extensive discussion, due to his multiple previous surgeries and challenging anatomy, the patient was deemed unsuitable for surgical treatment. There is some limited registry data to support TEER as a safe and feasible alternative to surgery in this cohort. He underwent successful implantation of two clip devices in the A2/P2 and A2/P2b positions via a trans-septal approach under a general anesthetic. Femoral venous access was used. Some useful learning points relate to the challenges posed by the unusual anatomy in terms of imaging and trajectory. No MVARC complications. Postoperatively the LVEF was 55% with a mean transvalvular gradient of 5mmHg and only mild (grade I) transvalvular MR. At three months the patient reported an improvement of overall functional status. This successful case of “clip-in-ring” TEER illustrates one of the expanding indications for existing trans-catheter valvular therapies as well as the potential for creative application of TEER in helping patients with high surgical risk.
Abstract 15808: Sodium Glucose Co-Transporter-2 Inhibitors and Clinical Outcomes in Cancer Patients Treated With Anthracyclines
Authors: Ayman R Fath, Mostafa Aglan, Amro Aglan, Mahmoud Kabbani, Abdullah Eldaly, Anatole Trakhtenbroit, Prince Otchere
Journal: Circulation (2023)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been proven to improve clinical outcomes in heart failure (HF). However, there remains a paucity of data on the potential cardioprotective impact of SGLT2i in cancer patients receiving anthracyclines. Aim: To evaluate if SGLT2i use is associated with improved outcomes in anthracycline-treated cancer patients. Methods: Using TriNetX Global Research Network from 2013 to 2021, patients diagnosed with cancer and receiving anthracycline therapy were identified and categorized into those who were taking SGLT2i versus those who were not. A 1:1 propensity score matching was used to control for baseline characteristics between the two groups. Patients were followed for 2 years. The primary endpoint was all-cause mortality and secondary endpoints were new-onset HF, acute HF exacerbation, myocardial infarction, new-onset atrial fibrillation/flutter, and all-cause hospitalization. Results: A total of 82,369 anthracycline-treated cancer patients were identified. After propensity score matching application, 1,412 patients were included in our analysis (706 patients in each group). Patients on SGLT2i had lower rates of all-cause mortality (OR: 0.7 [95% CI: 0.56, 0.88]; P=0.002), acute HF exacerbation (OR: 0.64 [95% CI: 0.41-1]; P=0.048), and new-onset atrial fibrillation/flutter (OR: 0.52 [95% CI: 0.33, 0.8]; P=0.003) compared to those not on SGLT2i. The incidence of myocardial infarction, new-onset HF, and all-cause hospitalization were similar between the two groups (Figure). Conclusion: Among cancer patients receiving anthracyclines, SGLT2i were associated with lower rates of mortality, acute HF exacerbations, and new-onset atrial fibrillation/flutter and similar rates of myocardial infarction, new-onset HF, and hospitalization.
Abstract 13785: QT Prolongation and QT Variability Predict New-Onset Atrial Fibrillation in the General Japanese Population
Authors: Yuichi Ninomiya, Shin Kawasoe, Takuro Kubozono, Akihiro Tokushige, Kei Enokizono, Hiroyuki Kamada, Issei Yoshimoto, Yoshiyuki Ikeda, Hironori Miyahara, Koichi Tokushige, Mitsuru Ohishi
Journal: Circulation (2023)

Background: The QT interval, an electrocardiogram (ECG) parameter, can be corrected for heart rate to obtain the QTc, an indicator of ventricular repolarization widely used as a predictor of ventricular arrhythmia. Although prolonged QTc and atrial fibrillation (AF) development are linked, there are few reports of QTc variability and AF development. Purpose: To identify a relationship between QTc prolongation and variability and new-onset AF in the general Japanese population. Methods: This retrospective study evaluated the annual health check-up data of 103,304 adults (50,438 males; age, 54±15 years) without AF at baseline, between April 2005 and October 2018. Most participants underwent annual health examinations as recommended by the Japanese health welfare policy. The QTc times were calculated with the Bazett formula (QTc=QT/√RR), using the mean QT and RR intervals. QTc variability was evaluated as the difference between the maximum and minimum QTc values at multiple checkups. AF was diagnosed using a 12-lead surface ECG. The strength of the association between QTc prolongation and variability and new-onset AF was determined using logistic regression analyses. Multivariate analyses were adjusted for clinical variables (age, sex, obesity, hypertension, dyslipidemia, diabetes, estimated glomerular filtration rate, and habitual drinking). Results: The median follow-up time was 6 years. During follow-up, 341 (0.3%) new AF cases were recorded. Univariate analysis revealed a significant increase in new-onset AF in the QTc prolongation (odds ratio [OR] per 10 ms, 1.08; 95% confidence interval [CI], 1.03-1.13; p&lt;0.001) and the QTc variability (OR per 10 ms, 1.15; 95% CI, 1.07-1.23; p&lt;0.001). After adjusting for clinical variables, multivariate analysis revealed that QTc prolongation and variability were significantly associated with new-onset AF (OR per 10 ms, 1.09; 95% CI, 1.04-1.14; p&lt;0.001) (OR per 10 ms, 1.16; 95% CI, 1.09-1.24; p&lt;0.001). Conclusions: QTc prolongation and variability are associated with an increased risk of new-onset AF in the general Japanese population. Although they have been reported to be involved with the autonomic nervous system, the mechanism of this causal relationship requires further investigation.
Abstract 16147: Racial and Ethnic Differences in the Diagnostic Yield of Cardiomyopathy, Aortopathy, and Arrhythmia Genetic Testing and Frequency of Family Variant Screening
Authors: Spencer V Carter, Justin L Grodin, Vicente Morales Oyarvide, Eric D Peterson, Sadiya S Khan, Dianalee McKnight, Ana Morales, Emily Russell, Yi-Lee Ting, Ann Marie M Navar
Journal: Circulation (2023)

Introduction: Genetic testing for individuals with inherited cardiovascular conditions can guide treatment and aid in family screening. However, the diagnostic yield of pathogenic or likely pathogenic (P/LP) variants may differ by race and ethnicity because of a lack of diversity in population-based genomic databases. Methods: We evaluated the diagnostic yield (% tests with P/LP variants) of genetic testing for cardiomyopathy, aortopathy, and arrhythmia among probands undergoing testing at a large commercial laboratory (Invitae Corp.) from 9/2015-7/2022 for the most common racial and ethnic groups: Hispanic, Non-Hispanic (NH) Black, and NH White individuals. We used multivariable logistic regression to evaluate for differences in diagnostic yield by race and ethnicity adjusting for age, sex, payer, and number of genes tested. The ratio of the number of persons undergoing family variant testing (FVT) to the number with positive tests was determined, with Chi-square tests to evaluate for differences by group. Results: We identified 129,565 persons undergoing diagnostic genetic testing (n=9,157 Hispanic, n=16,287 NH Black, and n=78,740 NH White). Compared with White persons, the odds of a positive test were higher in Black and Hispanic persons for cardiomyopathy (OR 1.2, 95% CI 1.2-1.3, p &lt;0.001 and OR 1.3, 95% CI 1.2-1.4, p &lt;0.001, respectively) and aortopathy (OR 2.1, 95% CI 1.8-2.5, p &lt;0.001 and OR 1.9, 95% CI 1.7-2.2, p &lt;0.001, respectively), and higher for Hispanic persons for arrhythmia (OR 1.2, 95% CI 1.1-1.3, p &lt;0.001). The ratio of FVT to positive tests was significantly (p &lt; 0.001) lower for Black and Hispanic persons than White persons for cardiomyopathy (0.32, 1.19, and 1.51, respectively), aortopathy (0.77, 1.62, and 2.34, respectively), and arrhythmia (1.47, 2.23, and 3.33, respectively). Conclusion: Despite being underrepresented in population genomic databases, the diagnostic yield of genetic screening for cardiomyopathy and aortopathy was higher in Black and Hispanic persons compared with White individuals. The relative frequency of family variant testing was lower in Black and Hispanic than in White persons, indicating an opportunity to improve cascade screening in these groups.
Abstract 17728: Distribution and Predictors of Left Atrial Low Voltage Areas in Patients With Atrial Fibrillation Undergoing Catheter Ablation
Authors: Alireza Oraii, Munveer Thind, Masahiro Sekigawa, Erica Zado, Rajat Deo, Andrew Epstein, David S Frankel, Saman Nazarian, Francis E Marchlinski
Journal: Circulation (2023)

Background: Low voltage areas (LVAs) in the left atrium (LA) are associated with a higher likelihood of non-pulmonary vein triggers for atrial fibrillation (AF), and ablation of LVAs has been shown to reduce AF recurrence. This study aimed to assess the distribution and predictors of LVAs in a large cohort of patients undergoing AF ablation. Methods: This study included patients who underwent first AF ablation at the Hospital of the University of Pennsylvania between November 2020 and December 2022. Patients with prior LA ablation, cardiac surgery, sarcoidosis, or amyloidosis were excluded. All patients underwent voltage mapping with multipolar mapping catheters and pulmonary vein isolation. LVAs were defined as contiguous areas with a bipolar voltage &lt;0.5mV. The associations between preprocedure risk factors, echocardiographic findings, and LVAs were assessed using univariable logistic regression. All variables with a p value &lt;0.1 were entered in a stepwise, backward, multivariable model. Results: A total of 857 consecutive patients (mean age: 64.7 years, 34% women, 33% non-paroxysmal AF) were included. LVAs were identified in 132 (15.4%) patients, of whom 72% had LVAs in posterior wall, 47.7% in roof/anterior, 43.9% in septum, 24.2% in floor/inferior, and 16.7% in lateral wall. The multivariable model showed that age (OR per 1 year increase 1.05, 95% CI 1.03-1.08), heart failure/left ventricular cardiomyopathy (OR 2.1, 95% CI 1.4-3.3), sinus node dysfunction (OR 3.7, 95% CI 1.8-7.3), persistent/permanent AF (OR 3.2, 95% CI 2.1-4.9), and severe LA enlargement on echocardiography (OR 1.9, 95% CI 1.1-3.5) were independent predictors of LVAs. Conclusion: LVAs are identified in 15% of patients undergoing first AF ablation and are typically located along the posterior and anteroseptal LA. Presence of LVAs can be anticipated using a readily available preprocedure risk assessment. This information may influence preprocedure planning and choice of ablation strategy.
Abstract 15631: A Precision Medicine Approach to Predicting Pathogenicity Among Population Variants in Hypertrophic Cardiomyopathy-Associated Genes in the UK Biobank
Authors: Leonie M Kurzlechner, Courtney Bair, Gabrielle Monaco, Manasa Gurumoorthi, Ghaith Sharaf Dabbagh, Sujata Kishnani, Hanna J Tadros, Ravi Shah, Viraj Patel, Anwar A Chahal, Andrew P Landstrom
Journal: Circulation (2023)

Introduction: Genomic and precision medicine have opened the door to predictive genetic testing to identify those at risk of cardiac disease before its development. This is important for hypertrophic cardiomyopathy (HCM), the most prevalent heritable heart muscle disease. A major hurdle to accurate predictive testing is the markedly higher prevalence of HCM-associated variants than of disease. New approaches are needed to discern which disease-causative, “actionable,” variants. Objective: To develop and validate a precision medicine approach for predicting pathogenicity of population-identified HCM-associated variants. Methods: We used phenotypic and genotypic data from the UK Biobank (UKBB). We filtered for missense variants in “definitive” (ClinGen) HCM genes. Our novel precision medicine tool, DiscoVari , provides signal-to-noise (S:N) analysis comparing disease to population variant frequency to identify pathogenic genetic ’hotspots’. We used reverse phenotyping to correlate evidence of HCM and sequelae (sudden death, heart failure, ventricular arrhythmias, atrial fibrillation, chest pain, pacemaker/ICD) to S:N hotspots. Variants were re-evaluated using American College of Medical Genetics and Genomics (ACMG) criteria; those in S:N hotspots met PM1 criteria. Results: Variants of uncertain significance (VUSs) in HCM genes had a prevalence of 21.8% in the UKBB, with PM1 determining variant call in 25.7% [24.9-26.6] of HCM-gene variants. Using SN enriched for HCM (0.35% with HCM without PM1 and 0.83% with PM1, p &lt; 0.01). InterVar did not enrich for HCM (0.71% with HCM with PM1 and 0.51% without PM1). DiscoVari reduced the likely pathogenic/pathogenic (LPP) variant burden in individuals without HCM (11.8% compared to InterVar (25.9%, p &lt; 0.0001). DiscoVari enriched for LPP variants in those with HCM (36.1%, p &lt; 0.0001) compared to healthy individuals, while InterVar did not. Conclusion: VUSs are common in HCM genes in the population and PM1 is crucial for accurate variant classification. Incorporating DiscoVari S:N into ACMG guidelines improves prediction of variants associated with HCM, or subclinical cardiomyopathy.