tbuckley/cabot-search huggingface dataset:
Abstract 4139675: Short- and long-term impact of aspirin cessation in older adults: a target trial emulation.
Authors: Zhen Zhou, Katherine Webb, Mark Nelson, Robyn Woods, Michael Ernst, Rory Wolfe
Journal: Circulation (2024)

Background: The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD). Methods: Post-hoc analysis using a target trial emulation framework ( Table 1 ) applied to the immediate post-trial period (2017-2021) of a study of low-dose aspirin initiation in 19,114 adults aged 70 years and older (ASPREE; NCT01038583). Participants from Australia and US were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0 ( Fig 1A ). The two groups in the target trial were: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term), and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models. Results: We included 6,103 CVD-free participants (cessation: 5,427, continuation: 676). Participant selection flow chart is presented in Fig 1B . Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE and all-cause mortality (HRs, at 3 and 48 months respectively were, 1.23 and 0.73 for CVD; 1.11 and 0.84 for MACE; 0.23 and 0.79 for all-cause mortality, p &gt;0.05) but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p &lt;0.05) ( Fig 1C ). Similar findings were seen for all outcomes at 6 and 12 months, except for a lowered risk of all-cause mortality in the cessation group at 12 months ( Fig 1C ). Conclusions: Our findings support the safety of deprescribing prophylactic aspirin used for primary prevention in older adults.
Abstract 4139640: Differential progression of cardiac structure and function in transthyretin cardiac amyloidosis (ATTR-CA) following treatment with tafamidis and diflunisal
Authors: Rebecca Scharf, Alexander Schmidt, Ikram Ullah, Deepa Gopal, Omar Siddiqi, Frederick Ruberg
Journal: Circulation (2024)

Introduction: Transthyretin cardiac amyloidosis (ATTR-CA) is an important cause of heart failure for which tafamidis is the only FDA-approved therapy. Diflunisal is an NSAID that is also effective in improving cardiovascular outcomes in ATTR-CA and is utilized in regions where tafamidis is unavailable or cost-prohibitive. Data comparing the efficacy of these agents are lacking. Research Question: To compare longitudinal changes in cardiac structure by echocardiography and cardiac biomarkers among patients with ATTR-CA treated with tafamidis or diflunisal over 36 months. Methods: Among 425 sequential ATTR-CA patients seen at the Boston University Amyloidosis Center between 2016 and 2022, following exclusion for single visits (194) and for receiving TTR-silencer or multiple therapies (67), the final cohort was 164 patients: 109 were treated with tafamidis (ATTR-CA-T, 86% wild-type) and 55 with diflunisal (ATTR-CA-D, 54% wild-type). Echocardiographic wall thickness was re-measured by a single observer, while LVEF, global longitudinal strain (GLS, expressed in absolute value), NT-proBNP, troponin I, prealbumin, and creatinine were collected from the electronic health record at baseline and 36 months with differences between the measures calculated for each patient and compared using paired t-tests. Results: At baseline, while the ATTR-CA-D cohort was older and had a higher proportion of variant ATTR-CA (p&lt;0.001), the ATTR-CA-T cohort had more advanced disease as demonstrated by increased wall thickness, lower LVEF, worse GLS, higher creatine, and worse cardiac biomarkers (Table 1). After 36 months of treatment compared to baseline (n=23 for ATTR-CA-D and n=36 for ATTR-CA-T), the ATTR-CA-D group showed increase in septal thickness (0.5mm, p=0.04) and posterior wall thickness (0.6mm, p=0.006), while GLS (-5.6%, p&lt;0.001) and LVEF (-5.9%, p=0.02) were decreased. There were no significant echocardiographic changes after 36 months in the ATTR-CA-T group and cardiac biomarker change was similar. Conclusion: These data suggest that tafamidis may be more effective than diflunisal in arresting echocardiographic progression in ATTR-CA. Further studies are necessary to assess the association of these changes with cardiovascular outcomes.
Abstract 4139669: Evaluating Gender-Based Differences in Outcomes of Premature Coronary Artery
Authors: Abdul Wali Khan, Sayyeda Aleena, Karnav Modi, Zafar Ali, TALAL ASIF
Journal: Circulation (2024)

Background: Premature coronary artery disease (CAD) is an important cause of morbidity and mortality amongst the younger patient population and presents unique clinical challenges. Our study aims at evaluating gender and age-based differences in the presentation and outcomes among younger patients with premature CAD. Methods: Using the National Readmission Database, we identified patients admitted between 2016 and 2019 with a primary diagnosis of acute myocardial infarction (AMI). We focused our analysis on premature CAD, defined as males aged less than 45 and females aged less than 55 at, the time of the AMI diagnosis. We investigated potential differences in the type of AMI presentations, interventions received, and mortality rates among these premature AMI patients. Results: A total of 225,948 patients with premature CAD were identified, comprising 89,608 males and 136,340 females. ST-segment elevation myocardial infarction (STEMI) was a more common presentation among the younger population compared to older cohorts (33% vs. 26%, p&lt;0.001). Importantly, males exhibited a higher incidence of STEMI than females (40% vs. 28%, p &lt;0.001). Females with premature CAD were significantly less likely to undergo PCI compared to males (52% vs. 62%, p &lt;0.001), even after adjusting for STEMI (OR 0.77, p&lt;0.001). Additionally, female patients demonstrated higher mortality rates than males (2% vs. 1.6%, p &lt;0.001), persisting even after age adjustment (OR 1.15, p 0.017). No significant differences in the length of stay, incidence of cardiogenic shock, and implantable cardioverter defibrillator placement were noted between males and females. Conclusion: Our study showed that STEMI was more common in younger patients presenting with AMI. Males had higher STEMI rates, but females were less likely to undergo PCI after adjusting for STEMI. Females also had higher inpatient mortality. These findings highlight disparities that warrant further investigation to address potential gaps in care for young female AMI patients.
Abstract 4139550: Americans’ Views on Healthcare Coverage, Access, and Equity in the US: Implications for Cardiovascular Health
Authors: Sudheesha Perera, Rishi Wadhera, Dhruv Khullar
Journal: Circulation (2024)

Background: Increased healthcare coverage and access leads to better cardiovascular outcomes. Policymakers are currently assessing strategies to expand coverage and access through government programs, but Americans’ views on health care remain poorly characterized. Methods: We used the 2022 General Social Survey (GSS) to assess perceptions of US healthcare coverage, access, and equity. We examined responses to 3 questions for all respondents, and stratified by age, income, and political affiliation: (1) whether the rich have easier access to health care, (2) whether it is unfair that those with higher incomes can afford better health care, and (3) whether respondents would be willing to pay higher taxes to improve the level of health care for all. GSS survey weights were used to generate nationally representative estimates. Results: Our analyses included 3544 survey respondents (weighted mean [SD] age, 47.1 [17.9] years). The majority of US adults agreed that the rich have easier access to health care (79.5%, [95% CI 75.7%, 83.3%]). Overall, more than half of Americans believe that differential access based on income is unfair (56.5% [52.0%, 60.9%]), with significant variation based on political party affiliation (Democrats 70.8% [62.4%, 79.2%]) vs Republicans 34.0% [25.9%, 42.1%], p &lt; 0.001). In terms of expanding coverage, 10.7% [8.1%, 13.3%] of Americans were willing to pay higher taxes to improve the level of health care for all, with stronger support among Democrats than Republicans (20.3% [14.4%, 26.2%] vs 2.6% [0.6%, 4.5%], p &lt; 0.001). We found no statistically significant variation in responses based on respondent age and income. Conclusions: In this national study, we find that Americans’ views on healthcare coverage, access, and equity are divided along partisan lines. Despite broad agreement that access is inequitable, only 1 in 10 Americans are willing to pay higher taxes to increase health care coverage nationwide. These results may inform policy priorities around expanding care coverage – including preventative screening, guideline-directed therapies, and in-hospital care for cardiometabolic conditions – with the goal of improving cardiovascular health in the US.
Abstract 4139587: Age at First Diagnosis of Atrial Fibrillation and Longitudinal Cognitive Decline
Authors: Yujie Wang, Bin Wang, Han Cao, Mingkun Tang, Chen Yao, Ping Zhang, DONG LI
Journal: Circulation (2024)

Introduction: Evidence is limited to suggest possible associations between the age at first diagnosis of AF and cognitive decline. The two main goals of this study were: 1) to examine if a younger age at which AF onset occurs is linked to a higher rate of longitudinal cognitive decline; and 2) to ascertain whether AF duration may have a cumulative effect on cognitive decline over time. Methods: We retrospectively analyzed the Atherosclerosis Risk in Communities Study (ARIC) data from 1990 to 2013. Three cognitive tests were utilized to evaluate cognitive function: the Delayed Word Recall Test (DWRT), the Digit Symbol Substitution Test (DSST), and the Word Fluency Test (WFT). We divided participants into AF onset age groups (≤55, 56-65, and &gt;65 years old) and used follow-up data to investigate the impact of AF onset age on 14-year cognitive deterioration. We also used data from all previous visits to visit 4 to classify AF duration. The association was estimated using the Generalized Estimating Equations (GEE) model. Results: Table 1 demonstrates the effect of varying the AF onset age and duration on the estimated cognitive change over 14 years of follow-up using our linear models. Participants who experienced their first episode of AF before age 65 showed a significantly higher loss in global cognitive Z score, the DWRT, but not in the DSST (after adjustments) or the WFT. Notably, participants with AF durations longer than 6 years exhibited a larger reduction in overall cognitive Z score, the DWRT, and the DSST. However, only AF durations over 9 years were significantly linked with the WFT. We also found no evidence that physical activities, smoking status, or alcohol consumption were additional risk factors for long-term cognitive impairment. Conclusion: Our investigation of cognitive decline across 14 years in patients in the ARIC cohort found that earlier onset of AF was linked with faster longitudinal cognitive deterioration. Furthermore, a longer AF illness history was linked to a higher rate of cognitive decline. However, when examining various cognitive scores, the age of onset and disease duration had slightly varied effects.
Abstract 4139613: Orthotopic Heart Transplant in a Patient with Chronic Lymphocytic Leukemia: Challenges in Management
Authors: Ankitha Radakrishnan, Apurva Sharma, mehdi oloomi, Maria Giovanna Trivieri, barry love, Raymond Benza
Journal: Circulation (2024)

Description of Case: A 67-year-old female with a long-standing history of chronic lymphocytic leukemia (CLL, stage 0) on surveillance protocol, end stage heritable cardiomyopathy (titin mutation positive) with ejection fraction 15% and severe mitral regurgitation was referred to our center for advanced therapy evaluation. On evaluation, right heart catheterization showed normal filling pressures but decreased cardiac index (RA 4, PCWP 8, CI 1.6), so she was started on milrinone and listed for transplant as UNOS status 4 exception after extensive discussion regarding advanced therapies in the setting of her low-grade malignancy with favorable outcome. She underwent orthoptic heart transplantation (OHT) with DCD donor and ex-vivo perfusion. The preoperative total leukocytes count was 71,700/μl with mild anemia but no thrombocytopenia. Retrospective crossmatch was notable for flow cytometry crossmatch positive but CDC negative. The post-operative course was significant for an increase in total leukocyte count to 110,000/μl in absence of fever or infective source but was complicated with SVC stenosis at anastomotic site and thrombosis of the SVC and innominate vein necessitating thrombectomy and stent placement in the SVC. She also had bilateral pleural effusions for which she had bilateral chest tubes for three weeks post-transplant. Standard immunosuppression without induction was given and graft function was preserved with biopsies negative for rejection. Discussion: This case describes a successful OHT in a patient with long-standing chronic lymphocytic leukemia with a favorable outcome. OHT is the most effective therapy for end-stage heart disease, however historically cancer patients were considered ineligible for this therapy, given the increased risk with post-transplant immunosuppression. Though literature is limited, it is suggested that a careful selection of patients may have favorable outcome with slightly increased risk of cancer. These patients are at increased risk of infections and complications related to immunosuppression, which may exacerbate the immunocompromised state and potential rapid progression of underlying malignancy. Hematologic malignancies increase thromboembolism risk, as seen with this patient. A multi-disciplinary team approach involving oncology and infectious disease is integral for optimizing care in this complex population.
Abstract 4139725: Minimal Radiation Use for Aortic Valvuloplasty During Pregnancy
Authors: Angela Li, Eihab Ghantous, Jenica Thangathurai, Jeannette Lin, Jamil Aboulhosn
Journal: Circulation (2024)

Introduction: Valvular heart disease affects approximately 1% of pregnant women, with left-sided obstructive lesions such as severe symptomatic aortic stenosis (AS) carrying the highest risk. In AS patients of childbearing age, 95% have bicuspid aortic valve (BAV). For preconception intervention, percutaneous balloon aortic valvuloplasty (PBAV) is often favored over surgical valve replacement. This decision becomes more nuanced when a symptomatic patient is pregnant, as we need to weigh the benefits of relieving obstruction with the risks of fetal radiation exposure. Description of Case: 32 year old female with BAV presented pregnant at 10 weeks gestation with new symptomatic severe AS, mean gradient 49 mmHg, aortic valve area (AVA) 0.72 cm2. She reported dyspnea with minimal exertion and an episode of presyncope. After multidisciplinary meeting between congenital cardiology, obstetrics and cardiac anesthesia, decision was made to pursue PBAV. At 17 weeks gestation, she was placed under general anesthesia, after which a TEE was performed for aortic annulus sizing. A 10 Fr x 80 cm sheath was placed in the left femoral artery for catheter and wire exchange without need for fluoroscopy. Under TEE guidance, we crossed the stenotic valve via retrograde approach. Based on measured annulus size, we advanced a 20 mm VIDA balloon across the aortic valve and inflated the balloon to nominal volume with simultaneous rapid pacing. There was mild-moderate AS with moderate aortic regurgitation after PBAV, AVA 1.27 cm2. Total radiation exposure was 5 mGy with maximum collimation, low fluoroscopy frame rates and use of "fluoro-store". Patient tolerated procedure well without complications and was seen in follow up visit with significantly improved exercise capacity. Discussion: Studies have shown that interventions should be avoided during the first trimester of pregnancy when there is highest risk of fetal radiosensitivity, and to limit radiation exposure dose to less than 50 mGy. Our case demonstrates that transcatheter interventions can be safely performed during early second trimester of pregnancy with minimal radiation exposure and optimal results, with the use of multimodality imaging guidance and good radiation safety habits. It should be noted that any intervention can still pose a non-negligible risk to mother and fetus and should only be performed in symptomatic patients refractory to medical therapy, with consensus by a multidisciplinary cardio-obstetrics team.
Abstract 4139533: Epigenetic Factors Predict Incident Heart Failure with Preserved Ejection Fraction
Authors: Yan Sun, Gregorio Linchangco, Qin Hui, Maryam Rahafrooz, J Michael Gaziano, Peter Wilson, Lawrence Phillips, Jacob Joseph
Journal: Circulation (2024)

Background: Heart failure (HF) is a life-threatening aging-related syndrome with growing impact on the global population. It is estimated that &gt;8 million adults in the US will be living with HF by 2030. HF with preserved EF (HFpEF), defined by an ejection fraction ≥50%, frequently has delayed diagnosis and limited treatment options. HFpEF progression can be affected by both gene and environment via different molecular pathways, which can be assessed by epigenetic factors measured by DNA methylation (DNAm). Methods: The DNAm levels of peripheral blood cells at enrollment into the Million Veteran Program (MVP) were profiled using the Illumina’s EPIC array. After excluding samples with low quality or discordant sex, and merging with the phenotypic data, the multi-ancestry (~70%, 24%, 5.4%, and 0.6% are European, African, Hispanic, and Asian Americans, respectively) epigenetic association study in the MVP included 1658 with incident HFpEF and 33926 controls without any record of HF. Incident HFpEF was defined as the presence of a diagnostic code for HF after enrollment into MVP and a measured left ventricle ejection fraction ≥50% within 90 days of first appearance of HF diagnosis code. For each DNAm site, the association with HFpEF was examined in a multiple regression model adjusted for age, sex, race/ethnicity, calculated cell type proportions, and potential batch effects. Epigenome-wide significance (EWS) threshold (p&lt;6.6×10 -8 ) corrected for multiple testing was used to identify DNAm sites associated with incident HFpEF. Results: We identified 106 EWS DNAm sites associated with incident HFpEF across 22 chromosomes, including the most significant DNAm in chromosomes 9 ( AQP3 , p=2.50×10 -27 ), 17 ( SOCS3 , p=3.39×10 -26 ), 19 ( SBNO2 , p=2.64×10 -25 ), 6 ( FGD2 , p =1.49×10 -24 ), and 18 ( NDUFV2 , p=1.57×10 -24 ). Most of the identified DNAm (92 out of 106, 86.8%) showed negative association with incident HFpEF. After additional adjustment for body mass index and diabetes status, the associations of 54 and 47 DNAm sites remained EWS with incident HFpEF. DNAm age (years) predicts incident HFpEF (OR 1.045, 95% CI 1.039-1.052, p=6.52×10 -14 ) independently from chronological age. Conclusion: The significant epigenetic associations with incident HFpEF suggest the crucial role of epigenetic regulation in the pathogenesis of HFpEF. These findings may lead to novel targets for treatment and prevention which could eventually reduce the burden of HFpEF among the growing aging population.
Abstract 4139610: A Curious Complete Heart Block with Carfilzomib
Authors: Mohammed Shah, Naveed Rahman, Talal Al-Mohamad, Sejal Batra, Apurva Vyas
Journal: Circulation (2024)

Carfilizomib is a proteasome inhibitor used in the treatment of multiple myeloma. The incidence of arrhythmias according to one pooled analysis was 13.3%, mostly linked to mild supraventricular arrhythmias. We present a case of carfilzomib-induced complete heart block (CHB). A 66-year-old male with a history of restrictive lung disease on 2 liters (L) oxygen, moderate aortic stenosis and multiple myeloma presented with shortness of breath and mild chest discomfort that started earlier that day. His most recent chemotherapy with carfilzomib, cyclophosphamide, and dexamethasone was 3 days prior to arrival. Oxygen requirements increased to 15L. Laboratory findings showed elevated high sensitivity troponins (600s), elevated brain natriuretic peptide (800), creatinine of 1.86 above baseline of 0.9. Chest x-ray revealed pulmonary edema. Initial electrocardiogram (EKG 1) showed 2nd degree, type 1 atrioventricular block, which was new compared to a prior EKG. Subsequent EKGs showed alternating bundle branch blocks with LBBB and RBBB (EKG 2) that progressed to eventual complete heart block (EKG 3). Echocardiogram revealed an ejection fraction of 55-59% without wall motion abnormalities and unchanged valve pathologies. The patient was treated for acute heart failure with diuretics and fluid restriction. Cardiac catheterization was deferred as he did not have classic anginal symptoms. Oncology recommended discontinuation of carfilzomib. Electrophysiology recommended implantation of a permanent pacemaker (PPM) due to persistent complete heart block, which he successfully underwent, improving his symptoms. The general arrhythmogenic effects of carfilzomib are established, however there is limited data on the specific types of arrhythmias. This case suggests that carfilzomib can result in CHB. Additional monitoring or early discontinuation of carfilzomib should be considered to prevent severe conduction abnormalities resulting in morbidity and potential mortality. Further research is necessary to elucidate underlying mechanisms and risk factors associated with carfilzomib-induced conduction abnormalities and whether they resolve with discontinuation of the medication.