tbuckley/cabot-search huggingface dataset:
Abstract 14887: Sleep Disorders Increase the Risk for Calcific Aortic Stenosis
Authors: Nadim El Jamal, Thomas Brooks, Carsten Skarke, Garret A Fitzgerald
Journal: Circulation (2023)

Introduction: Circadian disruption has been implicated in the development of various cardiovascular diseases in several epidemiological studies. The role of molecular clocks in heart failure and vascular disease has also been extensively studied in animal and human models. However, studies assessing circadian rhythms in aortic valve disorders are lacking. We hypothesize that circadian disruption due to sleep disorders increases the risk for a diagnosis of calcific aortic stenosis (AS). Methods: We requested electronic health record (EHR) data from 8.8 million patients with ICD9 and ICD10 codes for sleep disorders and from 8.8 million patients without these diagnosis codes from the TriNetX Diamond network. We then ran cox proportional hazards models for the incidence of non-rheumatic aortic stenosis (ICD10 codes I35.0 and I35.2) after age 60 for patients diagnosed with sleep disorders (ICD10 G47-, ICD9 327-) before age 60 compared to patients with no sleep disorder diagnosis before age 60. We adjusted the models to include sex, BMI, and ICD codes for hypertension, hyperlipidemia, diabetes, and chronic kidney disease. We excluded patients with congenital aortic valve disorders, and patients with aortic valve procedures but no AS. Results: In our adjusted models, patients with any sleep disorder were at a significantly higher risk for being diagnosed with AS after age 60 (Figure). Analysing each individual sleep disorder we find that sleep apnea, hypersomnia, and narcolepsy are the main drivers for the association compared to other sleep disorders. The differences in adjusted and un-adjusted models indicate that a portion of the effect may be driven by cardiometabolic and renal risk factors. Conclusions: Circadian disruption due to a diagnosis of a sleep disorder increases the risk for developing AS. While some disorders are independent risk factors, in others the higher risk might be driven by the presence of known cardiometabolic and renal risk factors.
Abstract 12653: Plasma LTBP-2 is Associated With Myocardial LTBP-2 and Poor Prognosis in Dilated Cardiomyopathy
Authors: Kazuto Nishiura, Tetsuro Yokokawa, Tomofumi Misaka, Shohei Ichimura, Yusuke Tomita, Shunsuke Miura, Takeshi Shimizu, Takamasa Sato, Takashi Kaneshiro, Masayoshi Oikawa, Akiomi Yoshihisa, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2023)

Introduction: Cardiac extracellular matrix proteins provide structural support to the heart function and are associated with fibrosis in dilated cardiomyopathy (DCM). Latent transforming growth factor beta-binding protein 2 (LTBP-2) is a type of extracellular matrix protein, but the significance of LTBP-2 in patients with dilated cardiomyopathy is still unclear. Objective: To elucidate the significance of LTBP-2 in dilated cardiomyopathy. Methods: Plasma LTBP-2 levels were measured by Enzyme-linked immunosorbent assay in 131 DCM patients who underwent endomyocardial biopsy and 44 controls who had no history of cardiac diseases. Immunohistochemistry for LTBP-2, LTBP-1 (another LTBP family member), and Elastica-Masson staining were performed in endomyocardial biopsy specimens. DCM patients were followed up for cardiac death or ventricular assist device (VAD) implantation. Results: DCM patients had elevated plasma LTBP-2 levels compared to controls (104 vs. 57 ng/mL, P &lt; 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen (R = 0.311, P &lt; 0.001). Myocardial LTBP-2-positive fraction was positively correlated with myocardial LTBP-1-positive fraction (R = 0.444, P = 0.014) and fibrosis fraction estimated by Elastica-Masson staining (R = 0.387, P &lt; 0.001). In the Kaplan-Meier analysis, the high plasma LTBP-2 concentration group and the high myocardial LTBP-2-positive fraction group had more cardiac deaths or VAD implantations than low groups (P = 0.008 and P &lt; 0.001, respectively). Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with cardiac death or VAD implantation. Conclusion: Plasma LTBP-2 reflects myocardial LTBP-2 and can be a biomarker to predict adverse outcomes in DCM patients.
Abstract 17889: Impact of Continuous Positive Airway Pressure for Severe Sleep Apnea on Very Late Recurrence in Patients Receiving Catheter Ablation of Atrial Fibrillation
Authors: Nobuaki Tanaka, Masato Okada, Koji Tanaka, Yuko Hirao, Shinichi Harada, Naoko Miyazaki, Masatsugu Kawahira, Kohei Iwasa, Yasushi Koyama, Kenshi Fujii, Watanabe Heitaro, Yoshitaka Iwanaga, ATSUNORI OKAMURA, Katsuomi Iwakura
Journal: Circulation (2023)

Background: Sleep apnea (SA) represents a risk for arrhythmia recurrence following catheter ablation (CA) of atrial fibrillation (AF). Continuous positive airway pressure therapy (CPAP) is the established standard treatment for moderate to severe SA. While CPAP exhibits promise in reducing AF recurrences post-CA, the evidence is not entirely consistent. The impact of CPAP for severe SA on very late recurrence post-CA of AF has not been elucidated. Methods: This study employed a retrospective, single-center, observational design. Data were derived from SA screening tests routinely performed in patients scheduled for CA of AF in our facility. We defined severe SA as an apnea-hypopnea index (AHI)≥30 by a home sleep apnea test or polysomnography. After excluding patients already diagnosed with sleep apnea before CA, we enrolled 461 consecutive severe SA patients. We divided them into two groups according to whether they had more than 1-year usage of continuous positive airway pressure after CA (CPAP group) or not (non-CPAP group). CPAP usage was monitored through telemonitoring and regular follow-up visits at our outpatient clinic every three months. Very late AF recurrence was defined as AF recurrence more than 1-year after the index CA. Results: The age was 65±10 years, 17.6% were females, and 60.1% had non-paroxysmal AF. The mean AHI was 37.4±15.3. The CPAP group included 32.8% (n=151) and non-CPAP group 67.2% (n=310). The AF recurrence rates within 1-year post-CA were similar between the two groups (CPAP group vs. non-CPAP group, 17.2% vs. 15.8%, log-rank p=0.88). However, the very late AF recurrence rate was lower in the CPAP group than non-CPAP group (CPAP group vs. non-CPAP group, 5.6% vs. 15.4%, log-rank p=0.0089). Conclusion: Among the untreated severe sleep apnea patients at the time of the catheter ablation of AF, CPAP treatment during 1-year post-CA was associated with fewer AF recurrences beyond 1-year post-CA.
Abstract 17962: Lenalidomide Associated Coronary Thrombosis
Authors: Varshitha Kondapaneni, Krithika Muthyala, Nikky Bardia, Mariam Riad, Bassam Omar, Christopher Malozzi
Journal: Circulation (2023)

Background: Immunomodulatory drugs (IMiDs) including lenalidomide, are associated with improved outcomes in multiple myeloma (MM), despite a small risk of vascular thrombosis. Case: A 49-year-old male with dyslipidemia, insulin-dependent diabetes and MM presented with chest pain radiating to both shoulders. He was diagnosed with IgA Kappa MM two and half years ago, and received 6-month induction chemotherapy with RVD (lenalidomide, bortezomib and dexamethasone), followed by stem cell transplant; currently maintained on Lenalidomide 10 mg daily. Other medications included Ozempic, Tresiba, atorvastatin and Xarelto for a remote history of deep vein thrombosis. Electrocardiogram (EKG) showed inferoposterior myocardial infarction (Fig. A). Vital signs were stable and physical exam was unremarkable. Labs revealed normal renal function, mild anemia and peak troponin of 117,556 pg/ml. Decision-making: He underwent prompt left heart catheterization which revealed proximal occlusion of a dominant left circumflex coronary artery (LCX) with thrombus throughout (Fig. B). Other vessels had mild disease. Decision was to proceed with primary percutaneous coronary intervention (PCI), including clot extraction and addition of eptifibatide for 12 hours given the large thrombus burden, the extensive ischemic changes on EKG and the active chest pain. He underwent successful thrombectomy and deployment of 2 drug-eluting stents in the LCX, resulting in TIMI 3 flow (Fig. 3). He recovered well and was discharged on previous meds in addition to Eliquis (to replace Xarelto), clopidogrel and aspirin. Conclusion: IMiDs have improved outcomes in MM patients, at a small expense of increased venous, and less commonly arterial, thrombosis. Patients should be monitored closely, preferably under the care of an experienced cardiooncologist, with strict control of their cardiac risk factors and consideration of antiplatelet therapy to avoid potential coronary thrombosis.
Abstract 18672: Impact of Enhanced Artificial Intelligence on Clinic Burden From False Alerts of Insertable Cardiac Monitors
Authors: Jagmeet Singh, Andrew Radtke, Sarah Rosemas, Kevin T Ousdigian
Journal: Circulation (2023)

Background: AccuRhythm AI is a suite of cloud-based classification algorithms that filter and suppress false pause alerts and atrial fibrillation (AF) episodes transmitted by insertable cardiac monitors (ICMs). An enhancement to the AF algorithm (AI v2) reduces false AF alerts by 50% relative to the original AI (AI v1) but the impact of this improvement on clinic experience is unknown. Aim: Determine the projected annual impact of AI v2 on Pause and AF alerts in a real-world patient population. Methods: Real-world data were obtained from de-identified LINQ II ICM patients with ≥3 months of follow-up. Previously published performance of each AI algorithm broken out by patient reason for monitor were projected onto the data. Results were extrapolated to the average 200-ICM clinic. The study endpoints were true alert retention, false alert suppression, and clinic review burden reduction. Results: The dataset consisted of 16,301 ICMs with mean follow-up of 7 months. Reasons for monitor were Known AF (25%), Suspected AF / Cryptogenic Stroke (40%), Syncope (23%), and Other (12%). The mean number of alerts per patient-year was 17.9 AF and 4.3 Pause. Projection of AI v2 resulted in minimal loss (0.9%) of true AF and Pause alerts, annually, with no loss in Pause and 1.0% in AF. AI v2 reduced annualized false AF and Pause alerts by 91% (97.4% false Pause and 88.1% false AF reduction) relative to the ICM and 35% relative to AI v1. This translates to 401 and 22 annual review hours saved for a 200-ICM clinic, respectively. Conclusion: The AF enhancement provides a meaningful reduction to the average ICM clinic’s review burden by eliminating most false Pause and AF alerts while maintaining nearly all true alerts.
Abstract 13963: Redefining the Assessment of “Therapeutic” Platelet Response to Acetylsalicylic Acid
Authors: Udaya Tantry, Kevin Bliden, Parshotam Kundan, Danielle Kraft, Rueshil Parekh, Sahib Singh, Aravind Dilli Babu, Anika Shah, Paul A Gurbel, Rahul Chaudhary
Journal: Circulation (2023)

Background: Despite extensive investigations, the optimal assessment of the “therapeutic response” to acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between serum thromboxane (Tx)B 2 ; arachidonic acid (AA)-induced platelet aggregation (PA) by light transmittance aggregometry (LTA); aspirin reaction units (ARU) by VerifyNow aspirin test (VN), and pharmacokinetics (PK). Methods: Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy volunteers. ASA response was defined as &gt;95% inhibition of serum TxB 2, &lt;550 ARU by VN test and ≤20% AA-induced PA. Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. Results: ASA Response measured by VN, and AA-induced PA was achieved within 30 minutes of ASA administration. A good correlation was observed between VN ARU and 1 mM AA-induced maximum PA (r=0.80, p&lt;0.001), serum TxB 2 (r=0.76, p&lt;0.001), and inhibition of serum TxB 2 (r=0.87, p&lt;0.001). The relation between platelet aggregation and TxB 2 inhibition appears to be dichotomous, with only modest inhibition of TxB 2 (~50% inhibition) associated with marked inhibition of platelet aggregation. ROC curve analyses indicated that ≤558 ARU and ≤7% AA-induced PA were associated with &gt;95% inhibition of TxB 2 . A plasma ASA 686 ng/mL cut-off was associated with &gt;95% inhibition of serum TxB 2 , ≤7% 1 mM AA-induced PA by LTA, and ≤585 ARU. Conclusion: Our study demonstrated an important relationship between PD and PK parameters measured immediately following oral ASA and cutoff values for VN assay and LTA that is associated with &gt;95% inhibition of serum TxB 2 . We demonstrated that ~50% inhibition of TxB 2 is required to reach high levels of platelet function inhibition.
Abstract 17976: Delivery of Allogeneic Mitochondria Accelerates Revascularization in a Murine Model of Peripheral Arterial Disease and Reverses Metabolic Signatures of Endothelial Senescence
Authors: Colwyn Headley, Caroline Hu, Gladys Chiang, Beu Oropeza, Philip S Tsao, Ngan F Huang
Journal: Circulation (2023)

Introduction: Peripheral arterial disease (PAD) is characterized by limb ischemia and biological therapeutics to treat PAD are limited. PAD associated with mitochondrial dysfunction in both endothelial cells and skeletal muscle. Hypothesis: Therefore, we hypothesized that mitochondrial transplantation (mito-transfer) can alleviate the cellular abnormalities linked to mitochondrial dysfunction in PAD. Methods: Mitochondria from allogeneic fibroblasts were transferred into human microvascular endothelial cells (ECs) of varying passages (p5-14) by centrifugation. After mito-transfer (24h), the metabolic activity and proliferative capacity of ECs were respectively quantified by extracellular flux analysis and EdU incorporation into DNA. Results: Compared to non-manipulated ECs, mito-transferred ECs had lower oxygen consumption rates (OCR) related to mitochondrial respiration (basal, maximal, and spare respiratory capacity, and mitochondrial ATP production). No significant differences were observed in the extracellular acidification rates related to the glycolytic activity of ECs. However, the ATP index (ratio of mitochondrial ATP/ glycolytic ATP) of late passage (p10) ECs significantly decreased after mito-transfer. Furthermore, compared to non-manipulated ECs, mito-transferred ECs of late passage (p10-14) showed a 25% increase in proliferation. Mito-transfer to the ischemic limb induced a 2-fold increase in limb perfusion after 14 days (Fig. 1). Conclusions: Collectively, these data show that EC aging is associated with increased oxidative phosphorylation metabolism and that mito-transfer decreased the senescence-associated oxidative glucose metabolism of ECs, enhanced EC proliferation, as well as accelerated revascularization in PAD. Mito-transfer is a promising strategy to treat PAD to improve revascularization and mitochondrial function.
Abstract 17049: Specific Subspecies of High Density Lipoprotein are Associated With Arterial Stiffness in Youth With and Without Diabetes
Authors: Tomas Vaisar, Carissa Thornock, Scott Isom, Elizabeth T Jensen, Catherine Pihoker, Ralph Dagostino, Paul P Wadwa, Elaine M Urbina
Journal: Circulation (2023)

Introduction: Early vascular aging (EVA), a risk factor for cardiovascular disease (CVD), is evident in youth with diabetes. The mechanisms responsible for EVA are not well understood. Causal relationship of HDL-C with CVD is doubtful, but HDL particle concentration (HDL-P) and HDL function (cholesterol efflux capacity, CEC) are associated with incident and prevalent CVD independent of HDL-C. We investigated whether these metrics associate with EVA in youth. Methods: We studied three cohorts of youth with T1D (n=173), T2D (n=214) and healthy controls (n=116). We quantified total HDL-P and 6 HDL subspecies by differential ion mobility, serum HDL CEC (total and ABCA1-specific), and investigated their association with arterial stiffness (tonometric carotid-femoral pulse wave velocity, PWV) with multivariate regression. Results: PWV was not associated with total HDL-P in any of the three groups, but was associated positively with concentration of extra-small (xsHDL, 7.6nm, r=0.22, P=0.004) in T1D, small (sHDL, 8.2nm) particles in T1D (r=0.31, P&lt;0.0001) and T2D (r=0.17, P=0.02), and negatively with large HDL particles (lHDL, 11.5 nm) in T1D (r=-0.19, P=0.01). None of the HDL subspecies associated with PWV in healthy subjects. The association of sHDL with PVW remained significant after adjustment for age, sex, BMIz, mean arterial pressure (MAP), and diabetes status when analyzing T1D and controls or T2D and control subjects (Table 1). Both HDL-CEC metrics were significantly associated with higher PWV in T1D cohort but not T2D cohort, however, in multivariate models neither remained significant after adjusting the model for MAP (Table 1). Conclusions: A specific population of small HDL particles, but not HDL CEC, is associated with EVA, a predictor of CVD, independent of traditional risk factors and distending pressure (MAP). How the small HDL particles relate to EVA and whether they may be a novel target for intervention to prevent EVA in youth remains to be investigated.
Abstract 14172: Surgical Aortic Valve Replacement Using Contemporary Mechanical versus Bioprosthetic Valves in Patients Aged 50 to 70 Years: Long-Term Outcomes
Authors: Ayman R Fath, Amro Aglan, Abdullah S Eldaly, Bishoy Abraham, Ahmed Almomani
Journal: Circulation (2023)

Background: Choosing either a mechanical or a bioprosthetic valve during surgical aortic valve replacement (AVR) in middle-aged patients is still controversial, especially with contemporary advancements in valve technology. Aims: To evaluate long-term survival and major morbidity in patients aged 50-70 years undergoing AVR using contemporary mechanical and bioprosthetic valves. Methods: A retrospective study was performed using the TriNetX global database to identify patients aged 50 to 70 years who had primary isolated surgical AVR from 2014 to 2020. Patients who had transcatheter AVR, concomitant, or prior cardiac surgery were excluded. Patients were stratified into 2 groups: mechanical and bioprosthetic. A 1:1 propensity-score matching was performed to control for baseline differences between the two cohorts. The primary endpoint was all-cause mortality and secondary endpoints were stroke, major bleeding, and reoperation over a follow-up period of 8 years. Results: A total of 1,138 propensity-matched patients were included in each group. There was no significant difference in survival, stroke, or reoperation rates between the two groups. Survival probability at the end of the follow-up period was 76.6% in the mechanical group and 80.1% in the bioprosthetic group (HR, 0.946 [95% CI, 0.702, 1.276]) (Figure 1). A total of 137(12%) vs 119 (10.4%) patients had stroke in the mechanical vs the bioprosthetic group, respectively (HR, 1.08 [95% CI, 0.851-1.392]). A total of 19 (1.7%) vs 17 (1.5%) patients had reoperation in the mechanical, and the bioprosthetic valve group, respectively (HR, 1.01 [95% CI, 0.526, 1.951]). There were higher major bleeding events in the mechanical group, 266 (23.4%) vs 163 (14.3%) in the bioprosthetic group, (HR, 1.64 [95% CI, 1.353, 1.999]). Conclusion: Contemporary bioprosthetic valves could be a reasonable option for AVR in patients aged 50 to 70 years with less major bleeding risk and similar survival, stroke, and reoperation rates.
Abstract 18112: LVAD Recipient and Caregiver Perspective on Prognosis and End of Life Care: A Qualitative Study
Authors: Matthew Mignery, Aroosa Malik, Supriya Shore
Journal: Circulation (2023)

Background: For left ventricular assist device (LVAD) recipients and caregivers, accurate understanding of prognosis is central to shared decision making. Our study evaluates (i) patient and caregiver estimated survival after a LVAD and (ii) describes how patients and caregivers rationalize estimated survival. Methods: We conducted a qualitative study with 18 LVAD recipients and 9 caregivers using semi-structured interviews. Interviews were transcribed and coded, with themes identified using rapid qualitative analysis. Results: Included patients had a median (range) age of 60.5 (28-83) years, 12 (67%) were men and 10 (56%) received their LVAD as destination therapy (DT). Participating caregivers included 8 (89%) women supporting 5 (56%) DT LVAD recipients. Depression was reported by 7 (39%) patients and 2 (22%) caregivers. Reported quality of life was low for most participants [median EQ-VAS score 60 (range 25-70) for patients and 50 (range 20-80) for caregivers]. Only 6 patients reported willingness to trade survival in favor of better quality of life. In the event of cardiac arrest, 15 (83%) patients and 7 (78%) caregivers reported wanting CPR for themselves or loved one. Although most participants reported health concerns primarily relating to their cardiac health and LVAD complications, both patients and caregivers provided high estimates of life expectancy [median 16 (range 3-45) and 14 (range 3-32) years respectively]. We identified three themes explaining how LVAD recipients and caregivers rationalize their estimated survival (i) survivor’s bias (ii) optimism (iii) minimization. Exemplary quotes are provided in the Table below. Conclusions: Several patients and caregivers reported low quality of life with concerns around poor cardiovascular health and LVAD complications. However, their estimated survival frequently exceeded clinically observed survival. This suggests an opportunity for improving patient-physician prognosis communication.