tbuckley/cabot-search huggingface dataset:
Abstract 4139644: Unraveling the Impact of Giant Cell Myocarditis in Cardiogenic Shock: A Comprehensive Analysis of Incidence, Mortality, and Hospitalization Costs from the National Inpatient Sample (2016-2020)
Authors: Bekure Siraw, Hong Thoai Nguyen, Hemraj Paudel, Juveriya Yasmeen, Khalid Hussein, Satish Bastola, Kirthi Somarouthu, Jose Medina-Inojosa, Mohammed Hussein
Journal: Circulation (2024)

Background: Giant Cell Myocarditis (GCM), a rare and aggressive inflammatory heart disease characterized by infiltration of the myocardium by multinucleated giant cells and extensive inflammation, represents a clinical conundrum, particularly in patients with cardiogenic shock (CS). Despite its rarity, GCM's devastating impact necessitates thorough investigation. To address this gap, our study harnesses comprehensive data from the National Inpatient Sample (NIS), aiming to unravel the incidence and mortality patterns of GCM in the context of CS. Methods: Utilizing data from the NIS spanning from 2016 to 2020, we identified admissions for CS. Diagnosis of GCM was defined with an ICD-10 CM code of I40.1 in patients who have had endomyocardial biopsy (captured using ICD-10 PCS codes of 02BK0ZX, 02BK3ZX, 02BK4ZX, 02BL0ZX, 02BL3ZX, 02BL4ZX, and 02BL4ZZ) during the index hospitalization. Survey weights were used to compute national estimates. Sociodemographic variables, medical comorbidities, procedures performed during the hospitalization, and outcomes of index hospitalizations were coded using corresponding ICD-10 codes. Descriptive statistics were used to summarize the study population. Results: Between 2016 and 2020, there were 114 admissions for GCM in the context of CS. The five-year incidence of GCM among CS admissions was 0.015%. The cohort's mean age was 48.4 years (SD 15.7), with males comprising 58.8% of the population. Racial and Ethnic composition included 69% Whites, 10% Blacks, and 8% Hispanics. Notably, 95.6% of these admissions occurred in urban teaching hospitals. Pulmonary artery catheterization for hemodynamic monitoring was employed in 23.7% of the cases. Temporary mechanical circulatory support devices were utilized in 56.1% of the admissions, including intra-aortic balloon pump in 28.9%, percutaneous ventricular assist devices in 8.8%, and extracorporeal membrane oxygenation in 21.9% of cases. Additionally, 36.9% of the patients required mechanical ventilation, and 34.8% underwent heart transplantation. The overall mortality rate was 23.7%. The median length of hospital stay was 24.6 days (IQR 16.5), and the median hospitalization cost was $955,128 (IQR $794,708). Conclusion: GCM complicating CS poses a formidable challenge with high mortality rates, length of stay, and cost of hospitalization despite intensive care interventions, emphasizing the urgency for advanced treatment modalities and tailored management approaches.
Abstract 4139591: Characterization of cardiac allograft vasculopathy on serial coronary angiography of heart transplant patients
Authors: Brian Huang, Jose Roberto Tello Ayala, Roukoz Abou-Karam, Eugene Pomerantsev, Joseph Garasic, Ioannis Mastoris, Gregory Lewis, Akl Fahed
Journal: Circulation (2024)

Background: Cardiac allograft vasculopathy (CAV) continues to be a major source of morbidity and mortality in heart transplant patients. Serial coronary angiography is the recommended modality to monitor for CAV after heart transplant. Research Question: We aimed to characterize the incidence and distribution of CAV on coronary angiography in heart transplant patients. Methods: In a cohort of 465 patients who had undergone orthotopic heart transplant at a single center, we identified 2451 associated coronary angiograms. Coronary stenosis lesions were extracted to perform CAV grading on each angiogram following the International Society of Heart and Lung Transplantation (ISHLT) grading system. Kaplan-Meier curves were generated for CAV incidence across gender and race. McNemar tests for paired proportions were used to compare involvement of different coronary arteries. Results: Among 465 patients (age 53.8±12.6 years, 26.9% female, 75.9% white), the mean±SD follow-up time was 5.8±4.5 years, with 2451 associated coronary angiograms (5.3±4.2 angiograms per patient). Over the follow-up period, 156 (33.5%) patients experienced CAV with an average time after transplant for CAV diagnosis of 4.2±3.5 years. CAV incidence ranged from 9.0% at the first angiogram at around one year from the transplant date, to 24.5% at the 5th angiogram at around 5 years from the transplant date. Of those diagnosed with CAV, 12 (7.7%) underwent PCI at time of initial diagnosis and 44 (28.2%) underwent PCI during the total follow-up period. At time of diagnosis, 137 (87.8%) patients had ISHLT Grade I, 14 (9.0%) patients had Grade II, and 5 (3.2%) had Grade III CAV. There were significant differences in vessel involvement with CAV at time of diagnosis – 3.8% presented with left main (LM), 66.0% with left anterior descending (LAD), 27.6% with left circumflex (LCx), and 39.1% with right coronary artery (RCA) involvement, including the branches of each. There was markedly more main vessel (88.4%) compared to branch vessel (26.3%) CAV reported, likely due to limitations of coronary angiography in visualizing small vessel CAV. CAV incidence and severity was not significantly different across sex or race. Conclusions: Within a large transplant patient cohort, CAV incidence was high and mostly reported in main vessels with the LAD being the most involved. Further work could be done to optimize earlier and more effective detection of CAV.
Abstract 4140380: Forecasting Heart Failure: Seasonal Alignment of Heart Failure Outcomes in New York
Authors: Prerna Gupta, Ellen Brinza, Prateeti Khazanie, Pamela Peterson, Michael Ho, David Kao
Journal: Circulation (2024)

Background: Seasonal variations have been observed in heart failure (HF) hospitalization. Our objective was to identify specific factors that could contribute to seasonal variability using a large longitudinal dataset of HF hospitalizations. Methods: Hospital discharge data was obtained for all hospitals in New York state from 1994-2007. Records with a primary diagnosis of heart failure. Year and month of admission were used as predictors to evaluate outcomes of in-hospital mortality, population-adjusted daily rate of hospital admissions, and length of stay (LOS) using univariable regression including a sinusoidal model to assess seasonality of HF outcomes. Observations were then adjusted for multiple medical covariables including acute diagnoses such as asthma, COPD, and pneumonia, average local monthly temperature, and humidity at each hospital using data from the Global Historical Climate Network to identify modifiers of seasonal variability. Results: Among 949,907 records, median age was 76 (IQR 65-84 years old), and 54% female (510,945 records). The population-adjusted rate of HF admissions increased by 1.1 admissions/day/year, whereas in-hospital mortality and LOS decreased by -0.3%/year and -0.3 days/year respectively (p&lt;0.001 for all). Seasonal trends were identified for daily HF admissions (February peak, p&lt;0.0001), mortality (January peak, p&lt;0.001) and LOS (January peak, p&lt;0.01). Cosinor analysis revealed significant periodicity for HF admission rate (amplitude ±0.9/admits/day/100,000 people, p&lt;0.001), in-hospital mortality (amplitude ±0.47%, p&lt;0.001), and LOS (amplitude ±0.23 days, p&lt;0.01). No other patient characteristics were significant modifiers of seasonality. Odds of mortality were highest in July rather than January when adjusted for average local temperature but not humidity. Conclusion: Adverse outcomes in patients hospitalized with HF were significantly worse in winter months even when adjusted for concurrent diagnoses such as pneumonia. Local ambient temperature was the strongest modifier of the observed seasonality. Given increasing frequency of extreme weather events, additional work to determine mechanisms of this and other environmental risk factors is urgently needed.
Abstract 4138912: Clinical outcomes of cardiac synchronization with or without an implantable cardioverter defibrillator based on pooled data from 5 clinical trials: a patient-level meta-analysis
Authors: Ilya Shadrin, Lurdes Inoue, Gillian Schmidler, Michael MacKenzie, Daniel Friedman, William Abraham, John Cleland, Anne Curtis, Michael Gold, Valentina Kutyifa, Cecilia Linde, James Young, Anthony TANG, Sana Al-Khatib
Journal: Circulation (2024)

Background: Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with heart failure with reduced ejection fraction (HFrEF) and wide QRS. Whether CRT-defibrillators (CRT-D) reduce mortality more than CRT-pacemakers (CRT-P) remains controversial. Aims: To compare the clinical outcomes of CRT-D vs CRT-P using data from 5 landmark CRT trials, both overall and stratified by etiology of cardiomyopathy (ischemic vs non-ischemic), sex (male vs female), age (≥ 70 y/o vs &lt; 70 y/o), and QRS morphology (IVCD, LBBB, RBBB). Methods: We performed a meta-analysis of patient level data from 5 prospective CRT trials (MIRACLE, REVERSE, RAFT, COMPANION and MADIT-CRT). Inclusion criteria were CRT-P vs CRT-D status (randomized comparison only in COMPANION), age ≥ 18 y/o and LVEF ≤ 35%. Exclusion criteria included secondary prevention ICD, QRS &lt; 120ms, pacemaker upgrade, ventricular pacing indication, or missing data. Primary outcome was composite of time to heart failure hospitalization (HFH) or all-cause death. Secondary outcomes were time to HFH and death. Outcomes were analyzed using a frequentist Cox Proportional Hazards mixed effects model adjusted for 17 variables. Results: A total of 3407 patients met inclusion criteria. Relative to patients with CRT-P (n=843), those with CRT-D (n=2564) were of similar age (66 y/o, p=0.5), less often female (24% vs 34%, p&lt;0.001), and more often had ischemic cardiomyopathy (59.4% vs 52.4%, p&lt;0.001), Fig 1A. Primary outcome was similar across groups (HR 0.902 [0.752, 1.081], p=0.26), but all-cause mortality was lower with CRT-D vs CRT-P (HR 0.77 [0.603, 0.983], p=0.036), Fig 1B. Interaction analyses suggested lower all-cause mortality with CRT-D vs CRT-P in patients with non-ischemic cardiomyopathy (HR 0.502 [0.346, 0.726], p=0.0003) and patients age ≥70 y/o (HR 0.679 [0.502, 0.919], p=0.012), with significance preserved after Bonferroni correction (Fig 1B). Conclusion: In patients receiving CRT for HFrEF, those with CRT-D had lower all-cause mortality than patients with CRT-P, driven mainly by a lower mortality with CRT-D in older patients and those with non-ischemic cardiomyopathy. No significant interactions were noted between ICD&amp;sex or ICD&amp;QRS morphology.
Abstract 4139893: Observed to Expected GDMT prescription after HFrEF hospitalization for Medicare beneficiaries: A Candidate Hospital Quality Measure
Authors: Thomas Cascino, Hechuan Hou, Dennie Kim, Francis Pagani, Keith Aaronson, Kylee Funk, Lourdes Cabrera, Ahmad Hider, Russell Funk, Geoffrey Barnes, Daphne Watkins, Donald Likosky, Jeffrey McCullough
Journal: Circulation (2024)

Background: Despite well-known morbidity and mortality benefits, implementation of guideline-directed medical therapy (GDMT) for HFrEF patients remains suboptimal. Understanding the center-level variation in observed-to-expected GDMT prescribing could support targeted improvement initiatives. Hypothesis: The risk-adjusted observed to expected (O/E) ratio for GDMT prescribing would vary between hospitals and be associated with mortality and readmissions. Methods: This cohort study included 100% of Medicare fee-for-service beneficiaries admitted for HFrEF and discharged between Jan 2009 and Dec 2017. Patients were excluded if they were readmitted or died within 60 days of discharge. The primary outcomes were: (1) prescription filling of ≥2 of 3 classes of GDMT (proposed quality measure of GDMT; SGLT2i not yet approved for HFrEF) within 60 days and (2) composite endpoint of death and readmission within 61-120 days post-discharge. The exposures of interest were: (1) center O/E GDMT prescription ratios to evaluate interhospital hospital variability and (2) GDMT quality measure prescription. Risk adjustment was performed via logistic regression, conditioning on demographics, comorbidities, neighborhood distress score, and pre-admission medication utilization. Results: In total, 296,900 patients were treated at 1,917 hospitals. Patients had a mean (SD) age of 77 (12) years and were 47.0% female (n=139,398). BB, ACE/ARB, and MRA were filled by 56.5%, 48.5%, and 21.2% of patients, respectively. In total, 42% were prescribed and filled ≥2 GDMT classes. Interhospital variability existed in O/E GDMT prescription (Figure). The adjusted difference in GDMT quality metric prescribing was 23.2% between top and bottom quartile hospitals (52.6% and 29.5%). GDMT prescription was associated with a 5.98% (95% CI -5.5 - -6.46%) lower probability of risk-adjusted death or readmission per patient in the subsequent two months. Conclusions: Large-scale interhospital variability exists in GDMT prescribing for HFrEF patients. While optimal GDMT is indicated for all HFrEF patients, assessing center-level O/E GDMT prescribing enables comparisons against achievable performance benchmarks and should be considered a potential quality indicator.
Abstract 4139407: Association of Aortic Valve Calcium with Albuminuria: The Multi-Ethnic Study of Atherosclerosis
Authors: Ashkan Abdollahi, Maryam Sani, Mahsima Shabani, Bruna Scarpa, Michael Blaha, Colin Wu, Bharath Ambale-Venkatesh, Matthew Budoff, Jordan Strom, Jerome Rotter, Wendy Post, Roger Blumenthal, David Bluemke, Joao AC Lima, Seamus Whelton
Journal: Circulation (2024)

Background: Higher aortic valve calcium (AVC) burden is associated with an increased risk of cardiovascular disease (CVD) and non-CVD. Despite shared risk factors between AVC and chronic kidney disease (CKD), the association of AVC with incident albuminuria is unknown. Methods: We examined 5,464 MESA participants who had AVC quantified by cardiac CT at Visit 1 (2000-02), an eGFR of ≥60 mL/min/1.73 m 2 , a normal spot urine albumin to creatinine ratio (ACR) (&lt;30 mg/g at baseline), and at least 1 follow up ACR measurement. AVC was analyzed as a log transformed variable, due to its right skewed distribution, and categorized as 0, 1-99, and ≥100. Incident albuminuria was defined as ACR ≥30 mg/g. We performed multivariable Cox proportional hazard regression along with mixed-effect linear regression models to examine the association of AVC with incidence, and progression of albuminuria per 5 years follow up, respectively. Models adjusted for baseline eGFR, sociodemographic and CVD risk factors, with further adjustment for coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype. Results: At MESA Visit 1, participants had a mean age 61.6±9.9 years, 2894 (53%) were women, and 616 (11%) had AVC &gt; 0. During a median follow up of 14.2 years, 921 (17%) developed albuminuria. There was a significantly increased rate of incident albuminuria with higher AVC values (p &lt; 0.001) ( Figure ). In multivariable adjusted models, a higher risk of incident albuminuria was observed when AVC was examined as a continuous variable (per log-unit [AVC+1]) HR 1.05; p = 0.03 and for participants with AVC ≥100 HR 1.43; ( p = 0.02) compared to AVC=0, but not for participants with AVC 1-99 (HR 1.13; p = 0.29). A significant progression in log transformed ACR was observed for AVC as a continuous variable (β 0.03; p &lt; 0.001) along with participants who had AVC 1-99 (β 0.13; p &lt; 0.001), and AVC ≥100 (β 0.16; p = 0.001), compared to AVC=0. The associations between continuous AVC and incident albuminuria remained after further adjusting for CAC score ( p = 0.04), Lp(a) ( p = 0.03), and the APOE-ε4 genotype ( p = 0.04). The signal was consistent for ACR progression after further adjusting for CAC score ( p &lt; 0.01), Lp (a) ( p &lt; 0.01), and the APOE-ε4 genotype ( p &lt; 0.01). Conclusions: In a multi-ethnic cohort of participants free of CVD and CKD at baseline, AVC was independently associated with a higher risk of incident albuminuria and progression of ACR.
Abstract 4139017: Carotid Plaque Score by Ultrasound and its Prediction of Carotid Plaque Burden by MRI and Cardiovascular Events
Authors: Christopher Chew, Zeina Dardari, Alexander Razavi, Khurram Nasir, Kunihiro Matsushita, Francesca Santilli, Augusto Lavalle, Gerhard Albrecht, Vijay Nambi, Amer Johri, Bruce Wasserman, Omar Dzaye, Michael Blaha
Journal: Circulation (2024)

Introduction: Imaging modalities are crucial for enhancing atherosclerotic cardiovascular disease (ASCVD) risk assessment. With total plaque burden recently recognized as perhaps a superior predictor for ASCVD, there has been a shift toward measuring carotid plaque burden rather than only stenosis on carotid artery ultrasound (CA US). We aimed to assess the association between carotid plaque burden detected by CA US and carotid artery magnetic resonance imaging (CA MRI) and their predictions for ASCVD events. Methods: Participants free of known ASCVD who underwent CA US at Visit 4 and/or CA MRI within the ARIC cohort were included. A composite carotid plaque score (CPS, ranging 0-6) was derived from CA US based on plaque presence in the left and right common, bifurcation, and internal carotid arteries. CA MRI measures included total wall volume, maximum wall thickness, maximum stenosis, and lipid core area. Adjusted linear regression was used to identify prospective associations between the CPS and natural log-transformed CA MRI measures. Proportional hazard Cox analyses were used to determine the associations between the CPS/CA MRI measures and ASCVD events. Results: In this analysis, 6,149 participants had CA US data available, 1,456 participants had CA MRI data available, and 877 had both. The mean time between CA US and CA MRI was 9 years. The mean age at CA US was 63 years old, 58% were women, and 1,568 participants had an ASCVD event with a median follow up time of 20 years. The presence of carotid plaque on CA US was significantly associated with composite ASCVD events and stroke only. The CPS had stepwise higher HRs across increasing intervals (Table 1a) and was significantly associated with natural log-transformed CA MRI measures after adjustment (Table 1b) . C-statistics for models predicting composite ASCVD events and stroke were similar for both CA US and CA MRI. Conclusion: The CPS had an independent association with both ASCVD events and stroke alone. It had a similar significant association with key CA MRI measures, suggesting that the CPS may predict future carotid plaque on CA MRI. Thus, the CPS may be a simpler yet effective method to quantify subclinical carotid plaque and improve ASCVD risk assessment.
Abstract 4140259: Bioresponsive Liposomal Nanoparticle-based Co-Delivery of tPA and DNase I Lyses tPA-Resistant Neutrophil Extracellular-Rich Clots
Authors: Shruti Raghunathan, Dante Disharoon, Keren Hu, Hanyang Wang, Selvin Hernandez, Anirban Sen Gupta
Journal: Circulation (2024)

The nonsurgical standard of care for thrombosis is the administration of tPA. However, 40% of occlusive thrombi resist lysis by tPA. These resistant thrombi include both arterial and venous types, particularly those linked to ischemic stroke and deep vein thrombosis. Clot recalcitrance to tPA therapy is largely due to neutrophil extracellular traps (NETs), protein-rich extrusions of DNA that generate in blood clots following neutrophil recruitment and activation. However, the mechanism by which NETs contribute to tPA resistance remains unexplored. To investigate NET-dependent tPA recalcitrance, we developed several microfluidic models for NET-rich blood clots. In these models, NET-rich blood clots were characterized by a core-shell structure, with NETs most tightly intercalated in the shell, and thicker fibrin colocalized with NETs. Correspondingly, only the shell exhibited significant resistance to tPA therapy in fibrinolysis assays. We observed that neutrophil elastase (NE), the primary enzymatic component of NETs, reduced the efficacy of tPA while DNase I increased its efficacy in the absence of NETs. Therapeutic concentrations of tPA took 12.3±2.7 min to breach the tPA-resistant shell, which is significantly longer than the in vivo half life of tPA (5 minutes). DNase I, an enzyme that degrades NETs, restored tPA efficacy, allowing breach of the shell within 2.5 ± 1.2 min. Building on these findings, we hypothesized that localized co-delivery of tPA and DNase using nanoparticles could remediate clot recalcitrance while minimizing iatrogenic effects and protecting the drugs from degrading in circulation. We engineered tPA-loaded nanoparticles (tPA-NPs) decorated with a fibrin-targeting peptide, and DNase-loaded nanoparticles (DNase-NPs) decorated with a NE-targeting peptide. A thrombin-cleavable substrate was incorporated into tPA-NPs such that they degraded upon exposure to thrombin, and an NE-cleavable substrate was incorporated into DNase-NPs such that they degraded upon exposure to NE. Upon triggered release, the nanoparticles achieved a concentration of 2 µg/mL tPA and NET-lytic activity equivalent to 50 IU/mL DNase I respectively. In functional assays, the combination of DNase-NPs and tPA-NPs triggered complete clot dissolution within 12 min (n=4, p&lt;0.05). In conclusion, the functionalized drug delivery system achieved localized co-delivery of tPA and DNase, resulting in complete lysis of clots that are recalcitrant to traditional therapies.
Abstract 4139628: Postoperative Risk Stratification For Complex Congenital Heart Disease Based On Age-adjusted NT-proBNP
Authors: Huayan Shen, Zhou Zhou
Journal: Circulation (2024)

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is extensively utilized in the prognosis of cardiovascular disease for adults, but its clinical significance for pediatric cardiology is poorly understood. Objectives: This study aimed to explore the prognostic value of age-adjusted NT-proBNP (zlog-proBNP) in pediatric patients with CCHD. Methods: This retrospective study included 2681 patients with CCHD (median age at surgery, 10.6 months; male, 59%), and the median follow-up time was 3.0 years (range, 1 day–6.2 years). The primary endpoint was death, and the composite events were death and unplanned cardiac reintervention. NT-proBNP level was measured within 24 h after surgery and transformed into zlog-proBNP. Results: NT-proBNP level increased to a median absolute value of 3970 (interquartile range [IQR], 1352–9095), and a median zlog-proBNP value of 3.83 (IQR, 2.93–4.44) on postoperative day 1, reaching its peak at approximately 12h. Compared with patients with low zlog-proBNP value (≤1.96), those with very high zlog-proBNP value (&gt;5; hazard ratio [HR] for death, 9.78 [3.17-30.22, p &lt;0.001]; HR for composite events, 3.64 [1.95-6.79, p &lt;0.001]) had higher risk of death and composite events, followed by patients with high (&gt;3.8 to ≤5; HR for death, 5.27 [1.79-15.53, p =0.003]; HR for composite events, 2.28 [1.29-4.03, p =0.004]) and moderate (&gt;1.96 to ≤3.8; HR for death, 3.83 [1.31-11.17, p =0.014]; HR for composite events, 1.53 [0.87-2.69, p =0.139]) zlog-proBNP values. Conclusions: Zlog-proBNP demonstrates substantial prognostic significance in patients with CCHD, warranting particular clinical attention in those with a zlog-proBNP value &gt;5.