tbuckley/cabot-search huggingface dataset:
Abstract 12846: Sleep Quality and Cardiac Structure and Function in Individuals With Heart Failure With Preserved Ejection Fraction
Authors: Lena Mathews, Lisa R Yanek, Allison G Hays, Kavita Sharma, Sanjiv J Shah, Marie-Pierre St-Onge, Pamela Ouyang
Journal: Circulation (2021)

Introduction: Sleep disorders are associated with heart failure. The association of cardiac dysfunction with abnormalities in sleep have not been clearly elucidated. We examined the association of cardiac structure and function on echo with sleep patterns in participants with stable heart failure with preserved ejection fraction (HFpEF). Hypothesis: Greater cardiac abnormalities would be associated with greater impairments in sleep quality in HFpEF. Methods: We recruited participants with compensated HFpEF. We used 14-day actigraphy to measure night-time sleep quality (latency, efficiency, awake after sleep onset, movement and fragmentation) and quantity (sleep duration). We examined cardiac structure: (left ventricular diastolic diameter [LVDD], volume [LVEDVI], left ventricular mass index [LVMI]); function (ejection fraction, global longitudinal strain [GLS], E/e’ ratio, E/A ratio, left atrial volume index, mitral annular velocity e’, tricuspid regurgitation velocity). Associations between sleep and echo parameters were examined using linear regression adjusted for age, sex, race and body mass index (BMI). Results: Among 47 study participants, 40% were Black, 72% were women, with mean age 65(11 SD) years. Cardiac abnormalities and sleep duration were not associated. Higher LVMI was associated with higher night fragmentation (ß coefficient and 95% confidence intervals 0.95 [0.16-1.74]). Higher average E/e’ was associated with higher night movement (2.62 [0.55-4.70]), and sleep fragmentation (2.61 [0.36-4.87]). Measures of systolic function were not associated with sleep abnormalities. Conclusions: In HFpEF, greater abnormalities in cardiac structure (LV mass) and diastolic function (higher E/e’) were associated with more restless sleep. Our findings suggest a relationship between sleep quality and cardiac dysfunction in patients with HFpEF. Future research is needed to assess the directionality of this association.
Abstract 11195: Is Personalized Computational Model of Atrial Fibrillation Really Personalized?
Authors: Eric Lluch, Viorel Mihalef, Anamaria Vizitiu, Tiziano Passerini, Chloe Audigier, Henry Halperin, Mehdiyar Haschemi, Hiroshi Ashikaga, Tommaso Mansi
Journal: Circulation (2021)

Introduction: Computational modeling-guided, personalized electrophysiology (EP) intervention for atrial fibrillation (AF) is an emerging paradigm of precision medicine. In the published models, advanced imaging and invasive mapping achieve personalization of cardiac anatomy. However, EP cellular personalization is less developed, and parameters are often assumed to be uniform across individual patients Hypothesis: Anatomical personalization alone is not sufficient to recapitulate the individual clinical features of AF in personalized models. Methods: For each of 57 patients (66±10 yr, 30 persistent) referred for catheter ablation of AF, we constructed a personalized 3-D model using pre-ablation CT, invasive mapping, and Courtemanche-Ramirez-Nattel atrial cell model. In the pre-ablation model, we performed virtual ramp pacing with cycle lengths at 200-120ms within the coronary sinus to induce AF. AF was defined as being inducible when it persists for &gt;15s. Simulation was repeated for 5 different published sets of EP parameters of ionic currents. In total, &gt;10k simulations were performed on an NVIDIA V100 GPU cluster, using the Lattice Boltzmann method with spatial resolution of 0.5mm and temporal resolution of 0.05ms, achieving a runtime of 24s per 1s of simulation ( Fig. A ). Results: While 100% AF inducibility was expected in the personalized pre-ablation models, AF inducibility varied between 27% and 96% depending on the set of ionic parameters used ( Fig. B ). The large variability of AF inducibility indicates that those models are highly sensitive to EP parameters, therefore anatomical personalization alone cannot adequately constrain the individual features of AF. Conclusions: The patient-specificity of the current paradigm of modeling-guided, personalized EP intervention is limited. There is an unmet clinical need for incorporation of personalized EP as well as anatomical parameters to achieve true precision medicine.
Abstract 11555: Prevalence of Depressive and Anxiety Related Symptoms Among Patients Living with Hypertrophic Cardiomyopathy
Authors: Abdul Aziz Asbeutah, Lisa Salberg, John L Jefferies
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is a common heart condition that affects at least 1:500 individuals in the United States. Patients with HCM can suffer from life-threatening arrhythmias, requiring implantable cardiac devices and several limitations in daily life activities. Only limited data exist describing impacts on quality of life among these patients. Hypothesis: We hypothesize that patients living with HCM may suffer from an increased prevalence of depressive or anxiety related symptoms. Methods: Patients were approached via survey invitation on the Hypertrophic Cardiomyopathy Association (HCMA) website. Surveys were made accessible to all the members of the HCMA who had provided an active email address. Survey data were collected via the HCMA and de-identified for subsequent analyses. Demographic variables along with 40 questions assessing signs and symptoms of depression and anxiety were included. Answers to questions ranged from never to nearly always and were transformed on a Likert scale. Results: Survey invitations were sent to 1425 patients/families with HCM. Of these, 737 (52%) completed the survey adequately. Around 93% of respondents were Caucasian, with a mean age of 52.1 ±1.4, and composed of almost an equal number of men and women. Around 70% of patients with HCM reported that they never or rarely felt worthless, helpless, hopeless, anxious or depressed. Meanwhile, less than 3% reported depressive or anxiety related symptoms on a daily basis. On the contrary, around 52% of respondents found it difficult to engage in daily exercise or activities such as lifting items and helping with household chores. Conclusions: In conclusion, patients with HCM infrequently suffered from depressive or anxiety related symptoms, while many reported increased levels of exercise-related limitations. Further studies are warranted to better understand the effects of HCM on the physical and psychological well-being.
Abstract 10459: Adenosine versus Diltiazem in Stable Supraventricular Tachycardia Unresponsive to Vagal Maneuver
Authors: Nithin P R, VIJU WILBEN, Vinil Kumar, Muralidhar Kanchi
Journal: Circulation (2021)

Introduction: The treatment of stable supraventricular tachycardia (SVT) in the emergency department includes intravenous adenosine. There is evidence to show that calcium channel blockers such as diltiazem have a better conversion rate. This study was conducted to determine the relative effectiveness and to examine the adverse effects of these drugs on converting stable SVT into sinus rhythm. Methods: A prospective randomized controlled study with one group receiving an intravenous bolus dose of 6mg adenosine followed by 12mg if conversion not achieved, and followed by diltiazem if not reverted, and other group receiving diltiazem 0.25mg/kg IV followed by 0.35mg/kg if conversion is not achieved which was followed by continuous infusion. Heart rate and blood pressures were continuously monitored for 1-hour post-conversion with monitoring of other adverse events results: A total of 52 patients with stable SVT were enrolled and were randomized into two groups. Of these 26 patients were given IV Adenosine in one arm and 26 patients were given IV Diltiazem. The conversion rates with adenosine 76.9% were statistically lesser than the diltiazem group 100% with the statistically significant p value of 0.023. The mean change in the blood pressures in either group was statistically insignificant and also the adverse events in either group had no significance. Conclusion: Calcium channel blockers such as diltiazem may be superior to adenosine in the emergency department in the treatment of stable SVT. In this study IV Diltiazem had better conversion rates than the IV adenosine bolus with minimal adverse events. Hence calcium channel blockers are found to be better, safe, and cost-effective in converting stable SVT.
CTNI-46. PHASE I OPEN-LABEL, SINGLE-CENTER, DOSE ESCALATION STUDY (NCT02423525) OF PULSATILE AFATINIB IN PATIENTS WITH BRAIN CANCER
Authors: Naveed Wagle, Tiffany Juarez, Jose Carrillo, Annie Heng, Jaya Gill, Minhdan Nguyen, Judy Truong, Najee Boucher, Ashley Archer, Hanh Nguyen, Natsuko Nomura, Venkata Yenugonda, Annamarie Allnutt, Garni Barkhoudarian, Daniel Kelly, Santosh Kesari
Journal: Neuro-Oncology (2021)

Abstract Afatinib is a small molecule, selective and irreversible ErbB family blocker. In preclinical models it effectively inhibits EGFR, HER2 and HER4 phosphorylation resulting in tumor growth inhibition and is approved for the treatment of EGFR-mutated metastatic non-small cell lung carcinoma and metastatic squamous cell lung carcinoma. Pulse dosing afatinib could potentially increase CNS exposure to reach therapeutic levels while allowing a recovery period to mitigate toxicities. We are reporting the results of a Phase I open-label, single-center, ‘3 + 3’ dose escalation study to determine the safety and tolerability of pulsatile Afatinib in patients with brain cancer and to define a recommended phase 2 dose. The study assessed the exposure of Afatinib in cerebrospinal fluid and serum, objective tumor response according to RANO criteria, progression-free survival, and overall survival, and will explore the association between molecular phenotypes and patient response. In total, 26 patients were screened and 24 were enrolled (median age 60, 78% male, 87.5% Caucasian, glioblastoma N=16, chordoma N=3, brain metastases N=2, meningioma N=1, anaplastic mixed oligoastrocytoma N=1). Patients had received a median of 2.5 prior treatments. The study proceeded through the 4 dosing cohorts without reaching dose-limiting toxicity: Cohort 1 (80mg every 4 days) N=3; Cohort 2 (120mg every 4 days) N=3; Cohort 3 (180mg every 4 days) N=7, including replacement patients; Cohort 4 (280mg every 7 days) N=11. Diarrhea (75%), rash (75%), nausea/vomiting (37.5%), fatigue (29.2%), anorexia (25%), and limb edema (16.7%) were the most common side effects. There were no CTCAE defined grade 4 toxicities. Grade 3 side effects infrequently occurred in the highest dosing cohort and once in each cohort 2 and 3. These results demonstrate that pulsatile Afatinib at a dose of 280mg every 7 days is safe and tolerable for patients with brain involving cancers.
Abstract 10671: Similar Left Ventricular Remodeling Despite Different Coupling Intervals of Frequent Premature Ventricular Contractions
Authors: Rajiv A Kabadi, Nicholas James, Juan F Torrado, Alex Y Tan, Karoly Kaszala, Kenneth A Ellenbogen, Huizar Jose
Journal: Circulation (2021)

Introduction: Left ventricular (LV) post-extrasystolic potentiation (PESP) and dyssynchrony (LVD) are proposed mechanisms that may trigger premature ventricular contraction-induced cardiomyopathy (PVC-CM). While long-coupled (LC) PVCs are characterized by higher LVD and lower PESP, short-coupled (SC) PVCs have higher PESP and lower LVD. Methods: Twenty-four mongrel dogs implanted with right ventricular epicardial pacemakers were randomized to short-coupled (PVC-SC; 200 to 220-ms, n = 10), long-coupled (PVC-LC; 320 to 340-ms, n = 7) bigeminal PVCs, or no PVCs (sham; n = 7). Holter monitors were obtained to confirm PVC burdens. Echocardiograms were performed at baseline and regular intervals up to 12 weeks after assignment to assess for LV remodeling by investigators blinded to group assignments. Intra- and inter-group comparisons were performed at each time point. PVC-CM was defined as LV ejection fraction &lt; 50%. Results: Holter monitors confirmed similar PVC burdens in PVC-LC and PVC-SC groups. After 12 weeks (Table 1), PVC-CM developed in 9 (90%) PVC-SC and 5 (71%) PVC-LC animals (p = 0.5368) with similar LVEF reduction in both groups (PVC-SC: 44.4 ± 1.5%; PVC-LC: 44.7 ± 4.0%; p = 0.9953) compared to sham (62.6 ± 1.5%). LV end-diastolic volume was greater in the PVC-LC (67.5 ± 4.6 mL) compared to PVC-SC (57.5 ± 2.7 mL; p = 0.0171) and sham (52.1 ± 1.5 mL; p = 0.0004) groups. LV end-systolic volume and indices of LV mass were similarly elevated in PVC-SC and PVC-LC groups compared to sham. Conclusions: Short- and long-coupled PVCs did not differentially impact the incidence or severity of LV remodeling in this translational animal model of PVC-CM. This finding is compatible with preliminary clinical observations that PVC coupling interval does not predict the development of PVC-CM in humans. Our data suggest that PESP and LV dyssynchrony play equally important roles in the development of PVC-CM.
Abstract 9961: Combination Therapy with Selective Endothelin Type A Receptor Blockade and Angiotensin-converting Enzyme Blockade Improves Survival of Congestive Heart Failure Similarly to Both Monotherapies: Study in Ren-2 Transgenic Hypertensive Rats with Aorto-Caval Fistula
Authors: Petr Kala, Matus Miklovic, Zuzana Honetschlagerova, Petra Skaroupkova, Zuzana Huskova, Vojtech Melenovsky, Josef Veselka, Ludek Cervenka
Journal: Circulation (2021)

Introduction: New therapeutic strategies for congestive heart failure (CHF) are needed, and the current knowledge, including our previous studies, suggests that targeting the endothelin (ET) system could be a promising approach. Hypothesis: Chronic selective blockade of ET type A (ETA) receptors combined with angiotensin-converting enzyme inhibitor (ACEi) would attenuate the course of CHF induced by volume overload achieved by the creation of the aorto-caval fistula (ACF). Methods: ACF was created in Ren-2 transgenic rats (TGR), a model of angiotensin II-dependent hypertension, at the animal age of 8 weeks. Two weeks later the animals were randomly divided into four groups and the therapy began: chronic selective blockade of ETA receptors with atrasentan (ETA block.) (5 mg.kg-1.day-1 in drinking water, n = 31), angiotensin-converting enzyme inhibitor (ACEi) (trandolapril, 2 mg.L-1 in drinking water, n = 32), a combination of atrasentan plus trandolapril (ETA block. + ACEi) ( 5 mg.kg-1.day-1 + 2 mg.L-1 in drinking water, n = 31) or placebo (n = 30). Sham-operated TGR represented a control group (n = 8). The follow-up period was 20 weeks. GraphPad Prism 7 was used for statistical analysis with a log-rank (Mantel-Cox) test to analyze survival data. Results: All sham-operated rats survived till the end of the study. Contrary, all untreated CHF rats died by week 12. The treatment with the ETA block. or with ACEi similarly improved the survival rate, and the final rate was 45 % in ETA block. group (p &lt; 0,01) and 62 % in ACEi group (p &lt; 0,01), the combinational therapy (ETA block. + ACEi) improved survival rate over placebo (52 %, p &lt; 0,01) but not compared with both monotherapies. Conclusions: Our present results suggest that in ACF TGR, the combination treatment with ETA block. and ACEi did not markedly attenuate CHF-dependent mortality over both monotherapies. Thus, more preclinical research needs to be done to deeper understand the endothelin system in CHF.
Abstract 11164: Better Electromechanical Synchrony During Left Bundle Branch Pacing and His Bundle Pacing as Compared to Right Ventricular Pacing in Atrioventricular Block
Authors: Xueying Chen, YANGANG SU
Journal: Circulation (2021)

Objectives: To compare electromechanical ventricular synchrony when pacing from different sites including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His Bundle pacing (HBP), left bundle branch pacing (LBBP) and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSP ring ) in each patient during implantation. Methods: Twenty patients with complete atrioventricular block (AVB) indicated for dual-chamber pacemaker implantation were included. Unipolar pacing at different sites including RVAP,RVSP,HBP,LBBP and RVSP ring were successively performed in each patient while pacing characteristics and echocardiogram parameters were collected and compared. Results: Similar to HBP, narrower paced QRSd was found in LBBP as compared to RVSP ring , RVSP and RVAP(p&lt;0.001). LBBP showed comparable pacing parameters to RVAP or RVSP and were significantly better than HBP, with maintained cardiac function. For ventricular mechanical synchrony, TS-12-SD was significantly improved in LBBP(27.00±21.53ms) than RVAP(54.05±34.21ms, p=0.004) and RVSP(47.56±33.26ms, p=0.029) but similar to HBP or RVSP ring . Among these pacing strategies, negative values of interventricular mechanical delay(IVMD) were only identified in LBBP(-20.16±18.47ms), significantly different from RVAP(33.68±30.98ms), RVSP (21.68±22.02ms), HBP (4.74±19.04ms) and RVSP ring (14.56±26.76ms(all p&lt;0.001). Using Pearson’s analysis, Sti-LVAT was found to be positively corelated with QRS, IVMD, TS-12-SD, LVEDV and LVESV while a negative relationship could be observed for LVEF. Conclusions: Similar to HBP, LBBP achieved better electrical and mechanical left ventricular synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV among these pacing strategies, in consistent with the RBBB pattern of paced QRS during LBBP.
Poster Abstracts
Journal: Hepatology (2021)

Background: The most common causes for an acute liver injury (ALI) in patients admitted to hospital has evolved over the past several decades. This can be attributed to largely by advancements in the treatments of viral hepatitis, alongside increasing co-morbidities in an ageing population. Our study aimed to assess the most common causes for an ALI (defined by ALT >700 IU/mL) in patients admitted to the acute assessment unit (AAU) over a 12 month period where COVID 19 was declared a global pandemic, and accounted for a rising proportion of hospital admissions. Methods: A search was performed between April 2020 and April 2021 of all patients admitted to the AAU with an ALT of >700 IU/mL. A review of patients electronic notes was undertaken to obtain information on the reason for admission, patient demographics and comorbidity, evidence of synthetic liver dysfunction and cause of ALI. Results: A total of 61 patients were admitted with a severe ALI over this 12 month period. There were an equal number of male (n=30) and female patients (n=31). The mean age was 58.7 years, range 23-99 years. The most common cause for an ALI was an ischaemic hepatitis (31.1%, n=19). Other causes for an ALI included;pancreatobiliary causes (21.3%, n= 13), drug induced liver injury (DILI) (18%, n= 11) which included acetaminophen overdose (n=4) and other drugs (n=7), COVID 19 infection (9.8% , n=6) and acute viral hepatitis (4.9%, n=3). The table below illustrates the difference in mean age and laboratory parameters between patients who experienced each type of liver injury. Inpatient mortality rates were highest in the patients with an ALI secondary to COVID 19 (66.7%, n=4) followed by those with an ischaemic hepatitis (36.8%, n=7). There were no reported inpatient deaths in patients with an ALI secondary to pancreatobiliary, drug induced or viral hepatitis. Conclusion: COVID 19 has been widely reported to cause acute rises in the serum transaminases, however this study demonstrates that the insult can occur in comparable degree to the other leading causes of ALI such as acetaminophen overdose and ischaemic hepatitis. These patients were older, with a higher mean ALT and creatinine. They were also found to have a higher degree of cardiovascular comorbidity which was in keeping with the risk factors associated with hospitalisation in COVID 19 infection. The higher mortality rates in these patients suggests a severe ALI as a marker of poor prognosis in patients admitted with COVID 19 infection.
Abstract 11490: Coronary Computed Tomography Angiography with Fractional Flow Reserve Outperforms Single-Photon Emission Tomography Myocardial Perfusion Imaging in the Observation Unit
Authors: Sahishnu Patel, Janessa Snippen, David Soma, Aaron A Smith, Abhinav Sharma
Journal: Circulation (2021)

Introduction: Coronary Computed Tomography Angiography (CCTA) and SPECT myocardial perfusion imaging (SPECT-MPI) are equally safe in evaluating patients presenting to the emergency department with acute chest pain. However, no study has compared the use of CCTA with Fractional Flow Reserve (FFR-CT) to SPECT-MPI in a chest pain observation unit (OU). We compared the performance of CCTA (with FFR-CT as needed) to SPECT-MPI for change in coronary artery disease (CAD) specific treatment (statins, antianginals, antiplatelets, and coronary revascularization) as well its impact on length of hospital stay (LOS). Methods: In 2020, our institution implemented an algorithm-based protocol in the OU to select patients appropriate for CCTA with explicit guidelines for management based on the results. We performed a retrospective analysis of 105 patients (52 SPECT-MPI patients from the period prior to initiation of the OU CCTA protocol who met criteria for CCTA, and 53 CCTA patients after CCTA protocol initiation). We performed two-tailed t-tests and chi-squared analyses to compare changes in treatment and LOS in both groups. Results: Patients in the CCTA group were younger (61 vs. 67 years, p=0.007), but there were no significant differences in CAD risk factors amongst the two groups. CCTA led to significant increase in statin, antianginal, and antiplatelet therapies, cardiac catheterization and revascularization within 6 months. There was no increase in LOS. Finally, CCTA did not increase acute kidney injury at follow up (Table 1). Conclusion: CCTA with FFR-CT significantly improved patient care by increasing appropriate preventative CAD treatment compared to SPECT-MPI while increasing the rate of revascularization without compromising length of stay or kidney function. In conclusion, protocol-based use of CCTA with FFR-CT is a more effective tool when compared to SPECT-MPI for chest pain patients admitted to the OU.