tbuckley/cabot-search huggingface dataset:
Abstract 18751: Emerging Frontiers in Hypertension Management: Consensus on Novel Approaches for Optimal Control
Authors: MS Hiremath, Chandrashekhar Ponde, Rakesh Jaswal, Aditya Kapoor, Nakul Sinha, Vijay Trehan, Arabinda Saha, K Kannan, Eric Borges
Journal: Circulation (2023)

Introduction: To establish a comprehensive consensus statement on hypertension management, incorporating contemporary evidence and drawing from the valuable real-world experiences of Indian physicians and cardiologists Methods: A virtual collaborative educational initiative was convened in May 2023, through a series of 8 nationwide virtual interactive meetings (n=87) at the forefront of hypertension care (3B Consensus Group). The cumulative clinical experience was approximately 2,500-man-years, who rated their level of agreement for 10 questions with each item on a 5-point Likert scale. This was preceded by a contemporary evidence-based discussion on the contemporary updates for hypertension. Weighted mean for the Likert scale was calculated and consensus was pre-defined as a score &gt; 100. GraphPad 9.5.1 and ANOVA were used for statistical analysis. Results: The highest agreement score was for, hypertension is an important cardiovascular risk factor in CKD (127.1), bisoprolol with conventional treatment is efficacious for managing MI and cardiac insufficiency (126.8), because of considerable variability in BP response to different drugs, personalized treatment approaches are essential to optimize the effectiveness of BP reduction (118.3), research is warranted to explore the importance of salt awareness in patients with hypertension (117.4), beta blockers including bisoprolol in the treatment of MI complicated with cardiac insufficiency effectively reduce cardiotoxicity, enhance myocardial response (114.4), treatment guided by ABPM can enhance outcomes (102.7) (Figure). The highest mean response scores (±SD, 95% CI) for consensus were for strongly agree (52.6±28.6, 95% CI 32.1 to 73) followed by agree (50.8±13.4, 95% CI 41.2 to 60.4) Conclusions: The physicians and cardiologists establish hypertension management consensus, emphasizing cardiovascular risk, bisoprolol efficacy, personalized treatment, salt awareness, and ABPM
Abstract 16868: Genetic Regulation of Branched-Chain Amino Acid Levels Does Not Increase Type 2 Diabetes Risk
Authors: David I Agamasu, Mingjian Shi, Nataraja Sarma S Vaitinadin, Venkatesh L Murthy, Ravi V Shah, Minoo Bagheri, Jane F Ferguson, Jonathan Mosley
Journal: Circulation (2023)

Introduction: The branched-chain amino acids (BCAAs) valine, leucine, and isoleucine are associated with incident type 2 diabetes (T2D). Prior genetic studies have provided conflicting results as to whether the BCAAs are causally related to T2D but are limited by a small number of genetic instruments associated with BCAA levels. Hypothesis: We hypothesized that polygenic predictors that capture a broad set of genetic mechanisms regulating BCAA levels would clearly define the etiological relationship with T2D. Methods: We constructed and validated instrumental variables for each BCAA using well-powered datasets and tested their association with T2D using two-sample inverse variance weighted (IWV) Mendelian randomization (MR). Sensitivity analyses were performed to ensure the accuracy of the findings. We also tested whether instrumental variables for T2D, fasting insulin, and body mass index (BMI) were associated with BCAA levels. Finally, logistic regression was used to test whether a polygenic risk score (PRS) for T2D was associated with measured BCAA levels among 1220 participants in the Framingham offspring study (FOS) without prevalent T2D. Results: There were no significant associations with T2D for valine (beta=0.17 change in log-odds per standard deviation change in valine, [95% CI, -0.28 - 0.62], p=0.45), leucine (beta=0.19 [-0.30 - 0.68] p=0.45) or isoleucine (beta=0.02 [-0.54 - 0.59], p=0.94). In contrast, T2D was associated with each BCAA (valine: beta=0.08 per standard deviation change in levels per log-odds change in type 2 diabetes, [0.05 - 0.10], p=1.8x10 -9 ), (leucine: beta= 0.06 [0.04 - 0.09], p=4.5x10 -8 ) and isoleucine (beta= 0.06 [0.04 - 0.08], p=2.8x10 -8 ). The T2D associations were replicated in an independent population but not in a second population where T2D cases were removed. Similarly, a T2D PRS was associated with measured BCAA levels in the FOS study but not when incident T2D cases were removed. Positive associations were seen for fasting insulin and BMI, and the BCAAs by MR, and, in multivariable MR analyses, T2D and fasting insulin had independent associations with each BCAA. Conclusions: These data suggest that BCAAs are not mediators of T2D risk but may rather serve as biomarkers of T2D and higher insulin levels.
Abstract 18918: Outcomes of Patients With Transcatheter Aortic Valve Replacement (TAVR) and Cardiac Resynchronization Therapy (CRT): A Retrospective Analysis
Authors: Rohan Umrani, Martin Matsumura, Yaser Khalid, Trinava Roy, Neethi Dasu, Kirti Dasu
Journal: Circulation (2023)

Introduction: Many patients with TAVR have a pre-existing reduced LVEF &lt;35% and left bundle branch block (LBBB) requiring CRT-D for potential improvement in LV function and secondary prevention of sudden death. Few studies have examined patient outcomes in this specific subpopulation. The aim of our study was to see if this patient population had worse outcomes compared to patients with TAVR without CRT-D. Hypothesis: We hypothesized that patients undergoing CRT would have better outcomes. Methods: Patients aged &gt;18 years with TAVR and CRT versus TAVR alone were identified from the United States National Inpatient Sample (2015-2020). ICD 9 and 10 codes were utilized and multivariate regression analysis was used to estimate the odds ratios of in-hospital mortality, average length of stay (LOS), and hospital charges (TOTHC), after adjusting for age, gender, race, insurance, and hospital demographics (type, size, region, and teaching status). Propensity matching was performed using the Kernel method. Weighted analysis utilizing Stata 17 MP was performed. Results: This study identified approximately 324,563 patients with TAVR, of which 2,613 patients had CRT. The analysis revealed mortality (OR: 2.59, p&lt;0.025, CI: 1.13-5.94), length of stay (LOS) (+5.69 days, p&lt;0.0001, CI: 4.44-6.95), and TOTHC ($165,520, p&lt;0.0001, CI: 134,551-196,489) were increased for patients with TAVR and CRT compared to patients with only TAVR. Secondary analysis is described in Table 1. Conclusions: Our study revealed that patients with TAVR and CRT had worse outcomes including increased mortality, LOS, and TOTHC. Despite CRT, this patient subpopulation had worse outcomes compared to those with only a TAVR. We suspect that these patients either have a poor functional status at baseline or CRT may not have as much benefit for patients with TAVR. Further studies are required to further evaluate this patient population.
Abstract 18906: Post-COVID Hemodynamic Pathophysiology: Prevalence of Dysfunctional Breathing and Preload Insufficiency Using Novel Invasive Cardiopulmonary Exercise Testing
Authors: Bianca Honnekeri, Mohak Gupta, Deborah Paul, Kenneth A Mayuga, Adriano Tonelli
Journal: Circulation (2023)

Introduction: The pathophysiologic mechanisms underlying persistent post-COVID cardiorespiratory symptoms remain understudied, despite the significant worldwide prevalence. Invasive cardiopulmonary exercise testing (iCPET) is a novel investigation that can inform our understanding of underlying hemodynamic abnormalities. Research Question: What is the prevalence of dysfunctional breathing (DB) and preload insufficiency (PI) in post-COVID patients who undergo iCPET? Methods: We studied hemodynamic characteristics in a cohort of 52 post-COVID patients who underwent iCPET in a sitting bicycle. The protocol augments CPET with continuous hemodynamic and laboratory data from pulmonary artery catheterization and arterial line. PI is defined as abnormally low right atrial pressure during exercise and reduced peak cardiac output percentage of predicted. DB is characterized by exercise-induced oscillatory ventilation. Results: The study cohort had a mean age of 40.8 years, and 36 of the 52 patients (69.2%) were female. iCPET revealed the prevalence of only DB as 15.4%, only PI as 34.6%, both DB and PI as 34.6%, and neither DB nor PI as 15.4%. These 4 sub-groups were subsequently compared for analysis. Notably, the cardiac output percentage of predicted at peak exercise was significantly different between the 4 groups (95.4%, 81.2%, 85.1%, 102.9%; p=0.007). The differential between baseline (sitting) and peak (maximal exercise) right atrial pressure was also significantly different between the 4 groups (0.00, 0.056, 0.333, 4.875; p=0.026). Our study suggests that PI and DB are common entities noted in symptomatic post-COVID patients, and may co-occur. Conclusion: This study is a first step towards understanding the altered hemodynamics that drive common symptoms in post-COVID patients. iCPET yields physiologic mechanistic information that could inform targeted interventions.
Abstract 18674: Deep Phenotyping Arrhythmogenic MVP With Imaging and Genotyping Reveals Important Shared Genetic Etiology With Arrhythmia and Cardiomyopathy Genes
Authors: Ghaith Sharaf Dabbagh, Ruchi Agnihotri, Gurpreet Kaur, Gregory Fazio, Matthew Singleton, Jefferson Lee, Brian Schuler, Adnan Malik, Edmond Obeng-Gyimah, C. Anwar Chahal
Journal: Circulation (2023)

Introduction: Mitral valve prolapse (MVP) has a high population prevalence 2-4% with an arrhythmogenic subtype presenting with premature ventricular complexes (PVC) ventricular tachycardia (VT) and sudden death. There is a continued search for markers of MVP to help risk stratify patients. Hypothesis: Arrhythmogenic MVP shares genetic etiology with Mendelian causes of arrhythmia and cardiomyopathy Methods: Consecutive adult patients with arrhythmogenic MVP patients prospectively evaluated Results: A total of 33 cases (age 55±15 years, female 51.5%) presented with history of hypertension (33%), diabetes (3%), coronary disease (12%), atrial fibrillation (45%), bileaflet MVP (58%) and syncope (18%). ECG findings include inverted T-waves in inferior leads in 6%, pleomorphic PVC in 6%, Ventricular couplets in 51.5%, non-sustained VT in 73% and sustained VT in 33%; High PVC burden was seen in 55% of cases with burden 15±14%. Echocardiography noted LV ejection fraction of 55±8%, mitral regurgitations in 70% (severe 18%, moderate 27%, mild 24%), mitral annular disjunction in 39%, and Pickelhaube sign in 9% of cases. Cardiac magnetic resonance showed LVESV 113±119mm, LVEDV 117±70mm, and late Gadolinium enhancement in 48% with highest prevalence in basal inferolateral segment. PET-CT performed in 17 cases and showed fluorodeoxyglucose uptake in 24% cases, mostly in basal inferolateral segment as well. Genetic testing was performed in 23 cases and reported a putative pathogenic variant in 21.7%: FLNC (Exemplar case, Figure 1 ) cause of dilated cardiomyopathy, TBX5 cause of Holt-Oram syndrome, DSP cause of arrhythmogenic cardiomyopathy , TTN causes of dilated cardiomyopathy, MTO1 cause of mitochondrial hypertrophic cardiomyopathy. Conclusion: Full evaluation of arrhythmogenic MVP with multimodality imaging and genetic testing reveals high burden of fibrosis, inflammation, and candidate pathogenic variants.
Abstract 18703: No Time for Horseplay: A Case on a Traumatic Septal Defect
Authors: Talhah Z Siraj, Anjula Chib, Sasha Sharifi, Sophia Thang, Vivek Menon, Paul Volansky, MANDAR JAGTAP DO, Mehul Patel
Journal: Circulation (2023)

Background: A 74-year-old male with no past medical history presented to the clinic due to shortness of breath that had worsened over the past two weeks. He reports being “knocked over by a horse” about one month before and experienced chest pain immediately afterwards. A new holosystolic murmur was found prompting further evaluation. A walking test showed his oxygen saturation dropped from 98% to 81% on room air and was in respiratory distress. TTE revealed a large VSD of 1.5 cm with a left to right shunt, a dilated right ventricle measured at 4.9 cm, and severe pulmonary hypertension. Coronary angiography ruled out a prior myocardial infarction. RHC revealed an increase of oxygen saturation from the right atrium at 68.6% to 92% in the right ventricle. The patient was transferred to a facility where he underwent successful surgical VSD closure. He was discharged to rehab on post-operative day 8. He presented to the clinic one month later reporting resolution of his symptoms. Discussion: This patient with no past cardiac history presented with progressive dyspnea that was later identified to be caused by a trauma he experienced one month prior. The incidence of traumatic VSDs is quite low. Most VSDs are congenital in nature however few are reported to be trauma related. Trauma so intense that could cause a rupture in the septal muscle is quite intriguing. Prompt work up with imaging modalities such as TTE is the best next step for any trauma-related symptoms. Shared decision making with the patient and a multidisciplinary team will help to decide on a percutaneous or surgical repair of the defect. This case demonstrated a systematic approach to a unique presentation of a typically congenital condition.
Abstract 16988: Conventional and Regionally Distinctive Risk Factors for First-Onset Myocardial Infarction in Bangladesh. The Bangladesh Risk of Acute Vascular Events (BRAVE) Study
Authors: Rajiv Chowdhury, Aliya Naheed, Md Mostafa Monower, Sara Shahzad, Rubhana Raqib, Ishrat Tasmin, Sarah Spackman, Lisa Pennells, Adam Butterworth, John Danesh, Emanuele Di Angelantonio
Journal: Circulation (2023)

Background: South Asians may be particularly susceptible to premature myocardial infarction (MI) owing both to classic cardiovascular risk factors and distinctive practices more common in South Asian populations. Hypothesis: Identifying modifiable risk factors for MI in South Asian populations should inform prevention strategies. Goal: To study conventional risk factors and several distinctive South Asian characteristics and practices in relation to the likelihood of first-ever MI in Bangladesh. Methods: In a case-control study involving 8,133 first MI cases and 8,122 controls, we calculated odds ratios (ORs) for MI (adjusted, when appropriate, for age, sex, smoking status, history of diabetes, history of hypertension, family history of MI, and LDL-cholesterol) and assessed their potential public health impact using population attributable fractions (PAFs). Results: The mean (SD) age of first MI was 53 (11) years. Adjusted ORs (95% CIs) were 2.75 (2.53-2.99) for cigarette smoking, 2.33 (2.08-2.60) for parental history of MI, 2.26 (2.07-2.48) for history of hypertension, 1.79 (1.61-1.98) for history of diabetes, and 1.61 (1.55-1.67) per 1-SD higher LDL-cholesterol. The highest PAFs (95% CIs) were for current cigarette smoking (48.9% [46.1%-51.6%]), higher LDL-cholesterol (32.4% [30.2%-34.4%]) and history of hypertension (14.7% [13.2%-16.1%]). As for regionally distinctive practices, ORs were 4.05 (3.15-5.21) with biri smoking, 2.04 (1.48-2.81) with chewing tobacco, and 1.26 (1.05-1.51) with parental history of first cousin marriage. Conclusion: In a large case-control study, we confirmed the relevance of several conventional risk factors to risk of first-onset MI in the Bangladesh population. We also identified significant associations with MI of practices distinctive to South Asian populations, including indigenous modes of tobacco consumption and parental first-cousin marriage, apparently independent of conventional risk factors. These findings should help identify opportunities for cardiovascular disease prevention in South Asia that embrace both conventional and regionally distinctive risk factors.
Abstract 18924: Structural and Electrical Remodeling Differences in Ischemia-Reperfusion versus Non-Reperfusion Myocardial Infarction
Authors: masahiro sekigawa, Jonathan Salas, David Callans, Francis E Marchlinski, Robert Gorman, Cory Tschabrunn
Journal: Circulation (2023)

Background: Structural and electrical remodeling following myocardial infarction (MI) can result in the development of arrhythmogenic substrate and ventricular tachycardia (VT). Various clinical factors such as reperfusion status, and occluded coronary distribution can impact the size of post-infarction scar. Objective: To investigate the structural and electrical remodeling characteristics in 2 different porcine models of MI. Methods: Fourteen swine underwent anterior infarction via 180min balloon occlusion followed by reperfusion (IR Group, n=7) or chronic total occlusion by embolizing the mid-LAD with a coil (CTO Group, n=7). Cardiac MRI and electroanatomic substrate mapping (Thermocool ST-SF) and high-resolution activation mapping (Pentaray 2-6-2mm) was performed in all subjects 8-9 weeks following infarction. Low bipolar voltage area (&lt;1.5mV), very low bipolar voltage area (&lt;0.5mV), and CMR LGE intensity volume reconstruction (inHeart Medical) were assessed. Programmed stimulation from the Ventricular apex was performed for VT inducibility assessment. Results: The CTO group had more extensive low bipolar voltage area (CTO: 36±6cm 2 vs. IR: 23±12cm 2 , p=0.04) and dense low bipolar voltage areas (CTO: 20±7cm 2 vs. IR: 7±6cm 2 , p=0.01). LV EDV was similar (CTO: 122±14ml vs. IR: 136±38ml, np) and there was no significant difference in LVEF (CTO: 28±4% vs. IR: 26±4%, np) and CMR LGE scar volume (CTO: 12±3ml vs. IR: 12±4ml, np). Voltage mapping demonstrated clear significant differences in substrate size and LV Endocardial CMR LGE intensity was more homogeneous in the CTO group than the IR group (Figure). Monomorphic VT was inducible in all 14 subjects. A total of 19 VTs were induced in CTO group (range 1-4, TCL 241±33ms) and 12 in IR group (range 1-2, TCL 208±17ms). Conclusions: Creation of a chronic infarct results in a significantly larger area of abnormal arrhythmogenic substrate than 180 minutes of ischemia-reperfusion.
Abstract 17034: Outpatient Effort to Improve Medication Uptitration and Maintenance (OPTIMUM)
Authors: May Xac, Jeffrey P Chidester, Leiandie Hulet, Megan Kelly, Elizabeth Moss, Christina Chang, Jennifer Jones, Paige Della-Penna, Alpesh Amin, Nicholas Hendren, Sandeep R Das
Journal: Circulation (2023)

Introduction: Guideline-directed medical therapy (GDMT) reduces morbidity and mortality for patients with heart failure with reduced ejection fraction (HFrEF) starting as early as 30-days from initiation. Rapid GDMT titration programs have been shown to be effective in clinical trials. We evaluated the feasibility of a rapid GDMT clinical program in a safety-net population with HFrEF. Methods: Patients admitted to a large urban safety net hospital with newly diagnosed HFrEF (LVEF &lt;40%) were eligible for the program. Patients with end-stage renal disease, history of cardiogenic shock, or current homelessness were excluded. The 6-week program consisted of alternating in-person heart failure clinic visits and virtual visits with a multidisciplinary team of pharmacists, nurses, and physicians to adjust medications and to provide heart failure education. Intensities of GDMT prescription at the start of the program and at 3 months were compared using an institutional GDMT score ranging from 0-11 which accounts for drug classes (beta-blocker, ACE/ARB/ARNI, MRA, SGLT2i) and percent of target doses prescribed (Figure, panel A). Results: This pilot enrolled 20 patients (mean age 58.0 +/- 15.6 years, 35% women, 25% Black, 75% Hispanic). At enrollment, patients had an average GDMT score of 5.5 on 2.9 classes of GDMT. At week 6, 15 (75%) patients were prescribed all 4 classes of GDMT with a 2.7 increase in the GDMT score for an average score of 8.2 (Figure, panel B).This was sustained at 3 months. There were no safety events requiring ED visits or hospitalization during the program duration. Conclusions: In a safety-net health system caring for the urban poor, rapid GDMT up titration was feasible and resulted in increased GDMT intensity without clinical adverse events. Our experience supports the development of rapid GDMT titration programs even in clinical settings and patient populations which differ from those enrolled in clinical trials.
Abstract 17226: Role of <i>BMPR2</i> Mutation in the Development of RV Failure in Rat Experimental Pulmonary Hypertension
Authors: Kazunobu Ohya, Hirofumi Sawada, Yoshihide Mitani, NAOKI TSUBOYA, Mami Takeoka, Noriko Yodoya, Hiroyuki Ohashi, Hiromasa Ito, Ryuji Okamoto, Kaoru Dohi, Tomoji Mashimo, Kazuo Maruyama, Masahiro Hirayama
Journal: Circulation (2023)

Introduction: BMPR2 mutations are the major genetic risk factor for pulmonary arterial hypertension (PAH) and are associated with increased disease severity and worse survival. Although worsening disease severity and prognosis in BMPR2 mutation carriers has been explained by more severe pulmonary vascular disease (PVD), recent reports suggest that BMPR2 mutations affect right ventricular (RV) myocardium and its function independently of PAH. However, mechanism of dysfunctional RV in BMPR2 mutations carriers are unknown.[Hypothesis]Rats with Bmpr2 mutation have impaired RV function independently of PVD compared to wild-type (WT) rats. Methods: Bmpr2 mutant rats were generated by CRISPR/Cas9 genome editing. Monocrotaline (MCT)-PH model was generated in mutant rats and WT littermates and changes in RV function over time with disease progression were assessed by echocardiography and catheterization in rats with (n=23) or without tadalafil treatment (n=88) Results: In untreated setting, there were no significant differences in RV systolic pressure (RVSP) and RV function between the two groups on 21 days after MCT, whereas RV-fractional area change (FAC) and cardiac index (CI), assessed at later disease stage (23 to 25 days), were significantly lower in Bmpr2 mutant rats than in WT (RV-FAC: WT 41.0±8.3 vs Bmpr2 mutant 27.5±11.5%, p&lt;.0001; CI: 413.2±114.0 vs 263.0±92.9ml/min/kg, p&lt;.0001) at comparable RVSP (64.5±11.6 vs 66.7±8.0mmHg) but higher total pulmonary resistance index (TPRI: 0.16±0.06 vs 0.27±0.09mmHg/ml/min/kg, p&lt;.0001). In rats with tadalafil treatment, Bmpr2 mutant rats had significantly lower RV-FAC (34.4±8.2 vs 23.6±5.4%, p&lt;.05) and more severe RV myocardial fibrosis compared to WT littermates despite no significant differences in RVSP (75.4±8.7 vs 71.0±8.2mmHg) and TPRI (0.19±0.06 vs 0.22±0.08mmHg/ml/min/kg) on 30 days after MCT. Conclusion: In untreated setting, RV dysfunction in Bmpr2 mutant was associated with increased afterload due to exacerbation of vascular lesions; rats treated with PDE5i and with prolonged survival had reduced RV function at comparable afterload, indicating the importance of managing RV function under treatment of PAH.