tbuckley/cabot-search huggingface dataset:
Abstract 15247: Usefulness of Circulating Human Epididymis Protein 4 to Predict Outcomes After Transcatheter Aortic Valve Implantation
Authors: Carlos Giuliani, Hecht Sebastien, Jorge Nuche, Julio Ivan Farjat Pasos, Jeremy Bernard, Lionel Tastet, Rami Abu-Alhayja'a, Jonathan Beaudoin, Nancy Cote, Robert De Larochelliere, Jean-Michel Paradis, Marie-Annick A Clavel, Benoit Arsenault, Josep Rodes-Cabau, Philippe Pibarot
Journal: Circulation (2023)

Introduction: Plasma level of Human Epididymis protein 4 (HE4) has been shown to be associated with an increased risk of cardiac events in dilated and ischemic cardiomyopathies. Hypothesis: was to examine the prognostic value of HE4 in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: Three hundred sixty-two patients (mean age: 79.6 ± 8.2 years; 57.3% men) undergoing TAVI for severe aortic stenosis were prospectively enrolled in this study. The cohort was divided into two groups according to the median value of pre-intervention HE4 plasma levels (115 pmol/l). The primary endpoints were: 1) all-cause mortality and rehospitalization for heart failure (HF), and 2) composite endpoints of rehospitalization for HF and all-cause mortality. Results: Patients with higher HE4 plasma levels were older (81.2 ± 7.8 years vs 78 ± 8.3 years, p&lt;0.001) and presented with more global comorbidities (i.e.: diabetes mellitus, chronic heart failure, renal failure, Euroscore II, STS score and left ventricular ejection fraction; all p&lt;0.05). During a median follow-up of 2.5 (1.9-3.2) years, 34 (9.4%) patients were rehospitalized for HF, 98 (27.3%) patients died and composite endpoint 113 (31%). The 4-year survival rate was significantly lower in patients with higher HE4 plasma levels (44% vs. 71%; p&lt;0.001). In the multivariable Cox proportional hazard regression model adjusted for diabetes mellitus, chronic heart failure, coronary artery disease, chronic obstructive pulmonary disease, atrial fibrillation, Society of Thoracic Surgeons score, and left ventricular ejection fraction, patients with HE4 &gt;115 pmol/l was associated with a markedly higher risk of all-cause mortality (HR [95%CI]: 3.32 [1.96-5.60], p&lt;0.001). They also had higher 4-year rates of HF rehospitalization (13 vs 6%; log-rank p-value=0.015) and of the composite of HF rehospitalization and all-cause mortality (45 vs 18%; adjusted HR [95%CI]: 2.38 [1.50 - 3.78], p&lt;0.001). Conclusion: Elevated HE4 plasma levels are independently associated with a higher risk of all-cause mortality and HF rehospitalization following TAVI. This novel biomarker may be useful to enhance risk stratification and therapeutic decision-making.
Abstract 15749: Long-Term Vascular Events in Pregnant Women With Congenital Heart Disease: The Magee Obstetric Maternal and Infant (MOMI) ACHD Substudy
Authors: Anita Saraf, Paola Pastena, Morgan Hindes, Kathryn Berlacher, Arvind Hoskoppal, Janet M Catov, Andreas P Kalogeropoulos
Journal: Circulation (2023)

Introduction: Data on long-term post-delivery risk for vascular events, including cerebrovascular and thromboembolic (TE) events, among women with adult congenital heart disease (ACHD), are limited. Hypothesis: Risk for vascular events remains elevated in the long-term after delivery in pregnant women with ACHD. Methods: Data from the University of Pittsburgh Medical Center clinical data warehouse were linked to all deliveries from 2004 to 2020 in pregnant women with ACHD (N=430) and without ACHD (N=876), who were included in the Magee Obstetric Maternal and Infant (MOMI) study. Women were matched at the delivery level for age, delivery year, and race. Ischemic and TE vascular events were captured until 8/31/2022. Cerebrovascular events were captured with codes I6X.X (ICD-10) and 43X.X (ICD-9); venous TE events with I82.X, I26.X, 453.X, and 415.X; arterial TE with I74.X, I75.X, 444.X, and 445.X; and acute coronary events with I20.X, I21.X, I24.X, 410.X, and 413.X. Kaplan-Meier (K-M) estimates were used for incidence and compared with Cox proportional hazards models. Results: Baseline characteristics and pregnancy outcomes are presented in Table 1 . After a median of 5.1 (2.8, 8.8) years, women with ACHD experienced 24 cerebrovascular events (5-year K-M: 5.2%), compared to 8 events (5-year K-M: 0.3%) in controls (HR 7.00; 95%CI 3.14 - 15.6; P&lt;0.001), and 8 venous TE (5-year K-M: 2.6%) vs. 11 (5-year K-M: 1.0%) events, (HR 1.69; 95%CI 0.68 - 4.18; P=0.26), Fig. 1 . There were no arterial TE events. Only 1 woman (with ACHD) experienced an acute coronary event. Conclusions: Women with ACHD remain at elevated risk for cerebrovascular but not venous TE events in the long-term after delivery.
Abstract 14479: Compound Heterozygosity With Two Novel Mutations in MYBPC3 as a Cause of Severe and Early-Onset Hypertrophic Cardiomyopathy
Authors: Jose. M Sanchez-Moreno, CARMEN CARRERAS BLESA, Maria del Mar Rodriguez Vazquez del Rey, Juan Jimenez-Jaimez, Rosa Macias Ruiz, Francisco J Bermudez-Jimenez, Maria Dolores Garcia Roa, Laura Diaz Rueda, Ivonne J Cardenas, Francesca Perin
Journal: Circulation (2023)

Case presentation: A 8-year-old male was diagnosed with severe hypertrophic cardiomyopathy (HCM) after a cardiac arrest from which he was successfully defibrillated. Maximal wall thickness was 23 mm (z-score 6.36) on echocardiography. An implantable cardioverter defibrillator (ICD) was implanted and atenolol was started. After 4 ventricular fibrillation-terminating ICD shocks in the following 2 months, further treatment is under consideration. A genetic test identified the likely pathogenic intronic variant (c.1927+337G&gt;T) in the MYBPC3 gene. An additional variant in the same gene (p.Arg817Gly), of uncertain significance but potentially relevant for the phenotype, was also found. His 10-year-old sister was also diagnosed with severe HCM, genetic test identified the two previously referred variants and ICD was also implanted. In the 4-year-old one sister, who is apparently healthy, only the likely pathogenic intronic variant (c.1927+337G&gt;T) was found. Regarding their parents, both with no evidence of cardiomyopathy, c.1927+337G&gt;T variant was identified in the father, while p.Arg817Gly was present in the mother. Discussion: This clinical case is noteworthy as an example of compound heterozygosity in which each parent donates one alternate allele, being these alleles located at different loci within the same gen, which emphasizes the importance of family genetic testing. The variant of uncertain significance p.Arg817Gly appears to be a disease modifier, causing the phenotype to be expressed early and severely in the presence of the probably pathogenic intronic variant c.1927+337G&gt;T in MYBPC3. This deep intronic variant has not been described previously but was found in thirteen index cases referred for HCM and a history of familial sudden death at an early age, being overrepresented in the cohort of HCM in the north of Spain. Being a carrier of both these two novel variants appears to cause an extremely aggressive childhood-onset phenotype.
Abstract 12761: Pathogenic Genetic Variants in Patients With Heart Transplant Due to Ischemic and Non-Ischemic Cardiomyopathy
Authors: Mahsima Shabani, Brett B Heimlich, Hannah Poisner, Yan Ru Su, Alexander G Bick
Journal: Circulation (2023)

Introduction: Current clinical guidelines recommend offering genetic testing to all patients diagnosed with non-ischemic cardiomyopathy (NICM), particularly in patients with a strong family history. The utility of genetic testing more broadly in patients with end-stage heart failure requiring heart transplant (HT) is unknown. Hypothesis: Among patients with HT, prevalence of cardiovascular disease (CVD)-associated pathogenic/likely pathogenic (P/LP) variants is higher in those with NICM than those with ischemic cardiomyopathy (ICM). Methods: We performed targeted DNA sequencing of 120 mendelian CVD genes in 124 consented patients with a HT, enrolled in the Vanderbilt Cardiac Catheterization Lab Cohort between 2003 and 2021. DNA sequence variation was annotated as P/LP based on ACMG criteria. Results: Out of 124 participants with HT, 70 had NICM and 51 had ICM. 22.8% of the NICM group harbored a P/LP variant in TTN (n=5), LMNA (5), MYH7 (1), RYR2 (1), RBM20 (1), COL1A2 (1), PKP2 (1), and CASQ2 (1). 19.6% of ICM participants harbored a P/LP variant in LDLR (2), RYR2 (1), TTN (1), SDHA (1), MYH7 (1), SGCD (1), MYL3 (1), CASQ2 (1), and COL1A2 (1). In NICM and ICM patients with a P/LP variant, 94% and 100% had a family history of CVD, respectively. By comparison in those without a P/LP variant, 59% and 73% had a family history of CVD. Out of 124 patients, only 13 had genetic testing through their clinical care, all of which occurred post-transplantation. 5/13 of these patients had a P/LP variant. Conclusions: This retrospective study showed a significant yield of genetic testing in HT patients. Notably, the overall prevalence of P/LP variants was nearly identical between NICM and ICM patients, with a higher rate of CM-related variants in the NICM group. We suggest that a genotype-first approach of screening all HT patients for genetic mutations enables earlier identification of actionable variants in HT probands and their family members than the current phenotype-guided approach.
Abstract 16332: Atrial Fibrillation Monitoring in Patients on Ibrutinib
Authors: Ruchi Patel, Arushi Singh, Zhiying Meng, Abigail Baldridge, Nausheen Akhter
Journal: Circulation (2023)

Introduction: Ibrutinib increases risk of atrial and ventricular arrythmias, especially atrial fibrillation (AF). No guidelines exist for arrhythmia monitoring, but experts suggest 24h Holter assessments for patients at risk of new or recurring AF or with CHA2DS2-VASc score ≥2. We sought to describe current practices in cardiac event monitoring in high risk or symptomatic patients on ibrutinib. Methods: We performed a single-center retrospective analysis of 168 ibrutinib-treated patients with no prior AF or atrial flutter (AFL). Patients were followed from 2013 to 2022. Event monitor data was obtained by a single reviewer through chart review. Results: Among 168 patients followed over a median of 6.4 years, 44 developed AF/AFL (25%) with 31 (70%) with paroxysmal AF. Mean (SD) age at ibrutinib initiation was 66 (11.1) years. Fewer than half (n=50; 30%) were female. Event monitoring was performed for 31 (18.4%) patients, 18 (58%) during treatment and 13 (42%) after treatment completion ( Table 1 ). The most common monitoring reasons were palpitations (10, 32%) and assessing AF burden (9, 29%). Cardiologists outside electrophysiology and cardio-oncology ordered the most monitors (17, 55%). Monitors most captured unspecified SVT (11, 36%) or no significant findings (9, 29%). Monitors most likely resulted in no management changes (19, 61%). The most common management changes were: placement of DC-PM (3, 10%), discontinuing anticoagulation (AC) (3, 10%) and diagnosis of AF (3, 10%). Of note, 14 monitors were done after AF diagnosis of which 7 (50%) showed no AF. Conclusions: Even with increased risk of arrythmias, use of monitors was low across a cohort of 168 patients. Notably, 3 monitors were used to discontinue AC and 3 monitors found new AF. Recent studies show most AF/AFL in ibrutinib users occurs within the first 6 months of initiation which may inform decisions in screening. Further guidance and standardization are needed for the use of monitors in the ibrutinib population.
Abstract 17394: Minimally Invasive Delivery of Synthetic Cardiac Stromal Cells Improves Heart Repair in Pigs
Authors: Yuan Li, Ke Huang, Ke Cheng
Journal: Circulation (2023)

Introduction: Myocardial infarction (MI) is the primary manifestation of cardiovascular events. Synthetic cardiac stromal cells (synCSCs) were shown to promote cardiac repair after MI. Minimally invasive delivery of synCSCs embedded in hyaluronic acid (HA) hydrogel via intrapericardial cavity (iPC) injections in a porcine model may provide a unique dataset for cardiac regeneration therapeutics. Hypothesis: Minimally invasive delivery of synCSCs via iPC injection will improve pig cardiac function and cardiomyocyte (CM) proliferation. Methods: A pig MI model was created using coronary balloon occlusion, and Yorkshire male pigs underwent video-assisted thoracoscopic surgery for iPC injections. Cardiac function studies were conducted using MRI to measure left ventricle ejection fraction (LVEF) and the infarct area. Histology and immunohistochemistry (IHC) analyses were performed to investigate CM proliferation. Single nucleus RNA-sequencing (snRNA-sq) analysis was performed to identify key gene features and phenotype changes that may be affected by the synCSC treatment. Results: The iPC injection of synCSCs embedded in HA hydrogel improves cardiac function, enhances cardiomyocyte proliferation, and induces phenotype alteration in the pig MI model. MRI analysis depicts significantly attenuated infarct size and improved LVEF at Day 28 in the synCSC group. Histology shows reduced fibrotic percentage and improved infarct wall thickness. IHC analysis shows a significant increase in cardiomyocyte proliferation. SnRNA-seq elucidates immature cardiomyocytes with higher proliferation gene features. Conclusion: The results show significant improvements in pig cardiac function and CM proliferation. Interestingly, immature cardiomyocytes of a different phenotype emerged in the therapeutic group. These findings provide an unprecedented dataset to facilitate the clinical translation of cardiac tissue regeneration therapeutics.
Abstract 18373: Differential Effects of Hypertension and Aneurysm on Stiffness Properties of the Abdominal Aorta
Authors: Mario Figueroa, John Gedney, Victoria Mattia, Ying xiong, Rupak Mukherjee, Jeffrey A Jones, Jean Marie Ruddy
Journal: Circulation (2023)

Introduction: The serum and glucocorticoid inducible kinase-1 (SGK-1) can contribute to matrix remodeling in murine models of hypertension (HTN) and abdominal aortic aneurysm (AAA), a potential biomechanical link between these aortopathies. Utilizing aortic stiffness as a marker of pathologic remodeling. Hypothesis: We hypothesize that HTN causes an SGK-1 dependent increase in aortic stiffness to amplify AAA growth. Methods: AngiotensinII (AngII) infusion induced HTN in C57Bl/6 mice (WT;1.46mg/kg/day) with subset groups treated + periadventitial CaCl2 to induce AAA and + infusion of the specific SGK-1 inhibitor EMD638683 (2.5mg/kg/day;n=2-4 each). Abdominal aortic ultrasound was conducted on Day 0 and Day 21 to measure stiffness parameters (radial strain(RS), distensibility(D), pulse propagation velocity(PPV)). Aortic diameter (AoD) was obtained by ultrasound and systolic blood pressures (SBP) were measured by Coda tail cuff. Results: This HTN model has consistently resulted in &gt;30% increase in SBP and AAA induction did not effect SBP. Although the WT+AngII+AAA mice had 66+8% increase in AoD, dilation was not amplified beyond that of the WT+AAA mice (72+7%, p=NS). Treatment with EMD had no impact on SBP, but did significantly reduce AAA growth (WT+AAA+EMD=29+5%; WT+AngII+AAA+EMD= 24+3%), therefore despite ongoing mechanical tension, SGK-1 inhibition abrogated a pathway necessary for degenerative remodeling. Accordingly, aortic stiffness was differentially altered in HTN versus AAA. As indictors of increased stiffness, D decreased with HTN (p&lt;0.05 vs Day 0) and RS decreased with AAA (p&lt;0.05 vs Day 0), but SGK-1 inhibition had no effect, indicating that the matrix remodeling driving these mechanical parameters was not SGK-1 dependent. Conversely, PPV was increased in both aortopathies (WT+AAA, WT+AngII, WT+AngII+AAA; each p&lt;0.05 vs Day 0) but EMD infusion prevented elevation in PPV, suggesting SGK-1-dependent preservation of contractility. Conclusions: Although concurrent induction of HTN and AAA did not amplify AAA growth, these aortopathies differentially impacted aortic stiffness. Tracking PPV as an indicator of pathologic SGK-1 activity may represent a pharmacological target to abrogate dysfunctional aortic remodeling.
Abstract 18143: Sudden Death in Heart Failure (HF) With Preserved Ejection Fraction: Clinical Profile and Role of Atrial Fibrillation (AF) and HF NYHA Class
Authors: Rangadham Nagarakanti, April Slee, Sanjeev Saksena
Journal: Circulation (2023)

Introduction: Clinical risk factors for sudden death(SD) in patients with HFpEF have not been hitherto well characterized nor is the impact of concomitant atrial fibrillation (AF) on SD risk in HFpEF defined. Methods: We evaluated 1765 HFpEF subjects from the TOPCAT Americas trial to identify potential clinical markers for SD risk. We also examined the role of AF presentation, comparing pts in sinus rhythm (SR, n=1319) to pts in AF at study entry with two different AF presentations (Any AF or AF on baseline ECG) during a mean follow up period of 2.9 years. Results: AF on baseline ECG was independently associated with excess CV mortality (HR 1.46, 95% CI 1.10-1.95, P = 0.009). SD occurred in 77 pts (4.4%) of all HFpEF subjects. 20 SD victims had concomitant AF on baseline ECG (26 % of all SD). SD events were significantly more frequent in males (p=.002), in black or other minority ethnicity (vs. white; p&lt;0.001), diabetics (p=0.024), lower eGFR (p=0.035) and vascular disease (p=0.044). Multivariate Cox analysis identified significant increased SD risk in people with reduced eGFR (HR 0.98, CI: 0.97 to 1.00, p=0.005), reduced risk in females (HR 0.40, 95% CI 0.24,0.65, p&lt;0.001) and increased risk in smokers (HR: 2.16, 95% CI: 1.03 to 4.54, p=0.042). In unmatched or propensity score matched cohorts, neither Any AF or AF on ECG was independently associated with increased SD risk (Figure; p&gt;0.2). SD risk was also similar in early and advanced NYHA class HF. Conclusions: 1. SD risk in HFpEF is influenced by gender, race, lifestyle and systemic comorbidities. 2. In contrast to HF with reduced EF, SD risk is not impacted by concomitant AF, its presentation or HF NYHA class.
Abstract 17122: Role of a Dedicated Program in Early Recognition and Treatment of Transthyretin Cardiac Amyloidosis
Authors: Ashwin Pillai, Sabeena Arora, Abhishek Jaiswal
Journal: Circulation (2023)

Introduction: Clinical recognition of Transthyretin Cardiac amyloidosis(ATTR-CA) is rising. Lack of treatment options with disease reversing agents makes early diagnosis and institution of treatment crucial to clinical improvement. A dedicated ATTR-CA program might facilitate such goals. Aim: We report our early experience with initiation of a cardiac amyloidosis program on diagnostic and therapeutic intervals and clinical outcomes. Methods: Retrospective review of patients who are being treated with Tafamidis in our cardiac amyloidosis management program(CAMP) from March 2019 through May 2022 Results: 55 patients with ATTR-CA (47-male) aged 80±9 years; 45 with clinical HFpEF and NYHA class 2-3 limitations and at least one prior hospitalization related to heart failure(HF) were seen in our CAMP(Figure). Initial mean LVEF was 50±12%. 42 had LVH and 11 had biventricular hypertrophy. Mean LV septal &amp; posterior wall thickness were 1.54±0.37cm &amp; 1.44±0.29cm respectively. The median interval between onset of HF and diagnosis, and from diagnosis to initiation of Tafamidis were 4 months (Inter Quartile Range[IQR] 1-9) and 1 month (IQR 0-3) respectively. For HF management, 35 patients were maintained on loop diuretics, 34 on mineralocorticoid receptor antagonists, 21 on SGLT2 inhibitors, 12 on beta blockers, 7 on ARNIs, 6 on ACEI/ARBs, and 1 on digoxin. Medications were tolerated well with no reported adverse effects. At follow-up, 16 patients reported NYHA class 1, 15 class 2, 14 class 3 limitations. 3 patients required PCI after enrollment in the program. Follow-up echocardiograms were available for 36 patients with a mean EF of 50±11%. Conclusions: Given the irreversible nature of ATTR-CA, early diagnosis and initiation of treatment is vital to improving long-term outcomes. Instituting a dedicated CAMP results in shorter diagnostic and therapeutic lag times than those historically described.
Abstract 16716: Clinical Parameters Associated With Temporary Transvenous Pacing for Patients Presenting With Complete Heart Block
Authors: Nishad Barve, Rahul Prasad, Rohan Prasad, Gauranga Mahalwar, Nicole Mae Lao, Hanad Bashir, Caroline Mangira, Indiresha Iyer
Journal: Circulation (2023)

Introduction: Patients presenting with Complete Heart Block (CHB) are emergently referred for placement of a temporary transvenous pacemaker (TTVP) for hemodynamic stability. Data on the immediate management and outcomes of such patients are lacking. Methods: Data collected through retrospective chart review of patients presenting to the Emergency Department (ED) at 3 regional referral hospitals from 10/2017 to 9/2022 with a diagnosis of new CHB; included age, sex, clinical, laboratory and ECG data, medications, interventions and length of stay(LOS). Results: There were 230 patients (106 women), mean age 77 years. Of these 94 were on beta blockers, 55 on calcium channel blockers. Syncope, dizziness and dyspnea were common symptoms. Pause &gt; 3 seconds was seen in 50 patients. Sympathomimetics were used in 55 patients and 179 patients were admitted to the ICU. There was no statistical difference in demographics, clinical features, ICU utilization and LOS. A TTVP was placed in 72(31%) and a Permanent Pacemaker (PPM) prior to discharge in 182 patients, a median of 1 day from ED presentation. By site, there were 71, 74 and 85 patients of whom TTVP was placed in 38%, 15% and 40% and a PPM in 76%, 82% and 79% in the 3 regional centers. The median LOS was 3 days. Univariate logistic regression was used to assess for predictors of TTVP placement (SAS® Version 9.4, Cary, NC). Syncope, Initial SBP, Shock, Pause &gt; 3 seconds, Acute MI, and Serum K were associated with higher odds of patients getting TTVP. SBP &gt; 160mmHg was associated with lower odds of needing TTVP. Conclusions: TTVP was infrequently needed (31%) among patients presenting to the ED with CHB. Initial SBP, Shock, Acute MI, Pause &gt; 3sec and Serum K were associated with TTVP placement. Higher SBP was associated with lower odds of needing a TTVP. There seems to be a difference in TTVP utilization rate between centers. Prospective data related to the acute management of CHB is needed to identify variations in utilization of TTVP between centers.