tbuckley/cabot-search huggingface dataset:
Abstract 13558: Age-Dependent Change of Electrocardiographic Characteristics and Cardiac Events in the Long QT Syndrome Type-3 With E1784K Mutation of <i>SCN5A</i>
Authors: Hiroyuki Kamada, Keiko Shimamoto, Yuichiro Miyazaki, Akinori Wakamiya, Nobuhiko Ueda, Kenzaburo Nakajima, Tsukasa Kamakura, Mitsuru Wada, kohei ishibashi, Yuko Inoue, Koji Miyamoto, Satoshi Nagase, Yoshiaki Kato, Heima Sakaguchi, Yoshihiro Asano, Kazuhiro Takahashi, Wataru Shimizu, Mitsuru Ohishi, Kengo Kusano, Takeshi Aiba
Journal: Circulation (2023)

Introduction: The pathogenic variant of E1784K in SCN5A is known as an overlapped phenotype; long-QT syndrome type-3 (LQT3) and Brugada syndrome (BrS), however it is still unclear age-dependent changes of the ECG findings and which ECG parameters are associated with cardiac events (CEs) in LQT3 patients with SCN5A -E1784K. Methods: Total 79 LQT3 patients with SCN5A -E1784K (45 probands, 42 males, age 23±17 years, QTc interval: 500±33 ms) were enrolled from the NCVC LQTS registry (2003~2023). We retrospectively evaluated age-dependent change of the clinical characteristics, ECG parameters and those associated with CEs. Results: Overall, 14 (18%) patients had CEs (10 syncope and 4 ventricular fibrillation), in which 8 occurred under 25 years old, but 6 occurred more than 35 years old. Thus, we divided all into two groups: younger (n=51) or older (n=28) than 30 years old. The younger group shows higher prevalence of male and proband compared with older group, and half of the syncope occurred during exercise. In the ECG parameters, P-R interval and QRS width were significantly longer in older group, in contrast, presence of T-wave alternance, notched, biphasic T-wave and bradycardia were more prevalent in younger group although the QTc interval and QTc peak-end were not different between the two group. Univariate analysis for CEs shows that longer QTc peak-end interval and absence of family history of LQTS are associated with CEs in younger group, whereas in older group, not only the longer QTc peak-end interval and absence of family history but also the Brugada ECG were associated with CEs. Finally, multivariate logistic regression analysis for all patients revealed that longer P-R interval, QTc peak-end and absence of family history of LQTS were independently associated with CEs (p=0.049, p&lt;0.001, p=0.001, respectively). ROC analysis revealed that P-R interval ≥180 ms and QTc peak-end interval ≥86 ms were significantly related to previous CEs. Conclusion: In LQT3 with SCN5A -E1784K variant, ECG parameters were age-dependently altered and longer P-R and QTc peak-end interval as well as absence of family history of LQTS can be associated with CEs. Furthermore, in adult patients, more careful follow-up should be required for those with LQT3 overlapped with BrS ECG.
Abstract 17201: Referral Patterns and Clinical Outcomes in Patients With Severe Aortic Stenosis
Authors: Azin Vakilpour, Michael Levin, Emeka Anyanwu, Srinivas Denduluri, Jennifer N Lee, Tiffany Sharkoski, Srinath Adusumalli, Mahesh K Vidula, Juan Lopez-Mattei, Jesse Chittams, David B Jones, Carlton Hartwell, Michael Bolooki, Jamieson Bourque, Marielle Scherrer-Crosbie
Journal: Circulation (2023)

Introduction: Once aortic stenosis (AS) becomes severe, close clinical follow-up by cardiac specialists and timely aortic valve replacement (AVR) are necessary to optimize patient outcomes. Discrepancies exist in the care of AS. Hypothesis: Provider specialty impacts referral for AVR after an initial echocardiogram (echo) revealing severe AS, with greater referral by cardiac specialists vs. non-cardiologists. Methods: Patients were identified based on an echo finding of new severe AS from Jan 2019 to Dec 2022 in an academic health system and were compared based on the ordering provider’s specialty (cardiology or cardiac surgery specialist vs. non-cardiologist). The primary endpoint was the rate of AVR after the initial echo. Univariable and multivariable logistic regression were used to identify characteristics associated with referral for AVR. Results: The study cohort included 2,131 patients: 630 (30%) were referred to echo by a non-cardiologist, 992 (46%) by cardiology, and 509 (24%) by cardiac surgery specialists (Table). Patients referred to echo by non-cardiologists were older, more frequently Black, and more symptomatic, with a lower rate of vascular diseases and a higher rate of heart failure and kidney disease. Thirty-four percent of patients referred by non-cardiologists, 62% of patients referred by cardiology and 81% of patients referred by cardiac surgery specialists underwent AVR at a median time of 58, 64 and 24 days after their echocardiogram, respectively (P&lt;0.001). Echo referral by cardiology (OR: 2.76, P&lt;0.001), echo referral by cardiac surgery (OR: 7.50; P&lt;0.001), age (OR: 0.96, P&lt;0.001), Black race (OR: 0.60, P&lt;0.001), presence of &gt;=2 CV risk factors (OR: 1.99, P&lt;0.001), and &gt;=2 comorbidities (OR: 1.54, P=0.001) were independent factors associated with AVR. Conclusion: Provider specialty impacts referral to AVR after an echo with new severe AS despite baseline characteristic adjustment, with higher AVR rates by cardiac specialists.
Abstract 18579: Endocytic Adaptor Protein DAB2 is a Novel Atheroprotective Regulator in Atherosclerosis
Authors: Kui Cui, Yunzhou Dong, Beibei Wang, Kathryn Li, John Shyy, Hong Chen
Journal: Circulation (2023)

Introduction: Endothelial dysfunction and arterial inflammation are critically important for cardiovascular diseases such as atherosclerosis. Of major importance, they are among the predominant culprits that promote the transition from stable to vulnerable atheromas. Our pilot studies revealed Disabled Homolog 2 (Dab2) deficiency in endothelial cells (EC) results in endothelial dysfunction. However, the molecular mechanisms that direct Dab2 to combat endothelial dysfunction during atherosclerosis are completely unknown. Hypothesis: Dab2 prevents the progress of atherosclerosis by maintaining EC function and reducing inflammatory factors. Methods and Results: We examined the expression of endothelial Dab2 in human atherosclerosis patients and ApoE -/- mice fed a western diet (WD) for 12 weeks by immunoflurecent co-staining of VE-cadherin and Dab2 and observed drastically reduced Dab2 expression in the endothelium and intima of human fatty streaks and mouse atherosclerotic aortae. Genetic deletion of Dab2 in the endothelium of ApoE -/- mice on a WD for 12 weeks significantly increased atherosclerosis as revealed by Oil Red O staining of aortic roots and arches, suggesting that Dab2 could be a atheroprotective flow-responsive gene. Similar results were found in WT and EC-iDab2KO mice injected with AAv8-PCSK9 virus. RNA-seq of primary mouse aortic ECs (MAECs) isolated from WT and EC-Dab2iKO mice revealed Dab2 deficiency upregulated many inflammatory genes. qRT-PCR confirmed TNF-α and IL-6 were significantly upregulated in Dab2KO MAECs. Additionally, we observed an increase in Dab2 binding to NEMO in the absence of endocytic adapter proteins epsins via co-IP with anti-Dab2 in WT and epsin-deficient DKO MAECs. We also found three Klf4 binding sites present in the Dab2 gene promoter/enhancer and that overexpression of Klf4 upregulated Dab2 expression in a dosage-dependent manner. Conclusions: Our findings indicated the essential role of Dab2 in protecting the atherogenic endothelium by reducing macrophage accumulation and increasing plaque stability in the aortic roots, which may provide new anti-atherosclerotic therapeutics.
Abstract 18772: Transient Receptor Potential Cation Channel 6 (TRPC6) Deficiency Preserves Cardiac Mitochondrial Respiration and Attenuates Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Zhen Wang, Xuan Li, Jussara M Docarmo, Alexandre A Da, Ana C Omoto, Alan J Mouton, John E Hall
Journal: Circulation (2023)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by diastolic dysfunction, cardiac hypertrophy and mitochondrial (MT) dysfunction. TRPC6, a non-selective cation channel that mediates Ca 2+ influx, is expressed in the heart and has been suggested to regulate MT function and participate in pathological cardiac hypertrophy. However, the role of excessive TRPC6 activation in HFpEF is unclear. Hypothesis: We hypothesized that TRPC6 deficiency would attenuate generation of MT-derived reactive oxygen species (ROS), MT dysfunction, and cardiac dysfunction in a model of HFpEF. Methods: HFpEF was induced in TRPC6 knock out (KO) and wild-type (WT) control mice via a combination of high-fat diet (45% fat) and L-NAME (0.5 g/L in drinking water) administration for 10 consecutive weeks. Cardiac function was assessed using echocardiography under normal conditions and after dobutamine (DOB)-induced stress (0.75 μg/g i.p). At the end of the study, MT oxygen consumption rate and MT-ROS generation were examined in isolated cardiac fibers using OROBOROS respirometry. Results: After 10 weeks of HFD+L-NAME, WT mice developed diastolic dysfunction and cardiac hypertrophy, whereas TRPC6 KO mice exhibited preserved diastolic function (IVRT: 21.5±1.1 vs 16.3±1.2 msec and E/E’: -35±2 vs -31±2 in WT and TRPC6 KO, P &lt;0.05). During DOB stress test (10 mins after DOB injection), TRPC6 KO mice had greater increases in stroke volume (3.3±2.8 vs -2.7±2.0 μl, P &lt;0.05) and fractional shortening (10.4±2.8 vs 2.4±3.1%, P &lt;0.05) from baseline compared to WT mice. TRPC6 KO mice treated with HFD+L-NAME also exhibited higher MT oxygen consumption (136.7± 31.1 vs 101.1± 20.1 pmol/min/mg, P &lt;0.05) and lower MT-ROS generation (0.43±0.3 vs 1.46±0.5 pmol/min/mg, P &lt;0.05) compared to WT mice treated with HFD+L-NAME. Conclusions: This study demonstrates that TRPC6 deficiency attenuated diastolic dysfunction while preserving cardiac reserve capacity, improving MT respiration, and reducing MT-ROS generation in HFpEF induced by HFD+L-NAME. Targeting TRPC6 and its downstream signaling pathways may offer a promising therapeutic approach for future HFpEF treatments.
Abstract 18968: Safety and Efficacy of Shockwave Intravascular Lithotripsy in the Management of Calcified Coronary Arteries: A Systematic Review and Meta-Analysis
Authors: Pramod Kumar Ponna, Maha Hameed, Sadia Yaqoob, Rajvi Gor, Nishat Shama, Akhilesh Gonuguntla, Stewart Benton, Farhan Shahid, Fares Alahdab
Journal: Circulation (2023)

Introduction: Shockwave intravascular lithotripsy (SWL) aims to facilitate optimal stent delivery and expansion for improved blood flow in treating calcified coronary artery disease. We sought to assess the safety and efficacy of SWL in managing de novo calcified lesions, lesions after failed/sub-optimal pre-dilatation with conventional balloon-based devices, under-expanded stents, and in-stent restenosis. Methods: A comprehensive literature search (Medline, Embase, Web of Science, Cochrane, and Google Scholar) was performed for studies that evaluated SWL in managing calcified coronary lesions. Efficacy outcomes included residual stenosis &lt;30% and successful stent delivery with a low incidence of device delivery failure. Safety outcomes included procedural complications and major adverse cardiovascular events (MACE). MACE is a composite outcome of all-cause mortality, cardiac mortality, myocardial infarction, target vessel/lesion revascularization, and stent thrombosis. Event rates across the included studies were pooled in a meta-analysis using the random effects model. An overall estimate and 95% confidence interval were reported for each outcome. Heterogeneity was estimated using the I-squared statistic. Results: Out of the 1446 identified studies, 40 were included, with a total of 2718 patients. Residual stenosis &lt;30% was achieved in 91.3% of patients (95% confidence interval 89.7% to 92.6%). Device delivery failure occurred in 6.7% of patients (95% CI 5% to 9%). In-hospital MACE occurred in 6.1% of patients (95% CI 5% to 7.4%), 30-day MACE in 7.4% (95% CI 6.2% to 8.8%), 6-month MACE in 8.3% (95% CI 7.1% to 9.6%), and 1-year MACE in 10% (95% CI 8.7% to 11.4%). Conclusions: SWL is a safe and efficient calcium modification intervention with high clinical success, minimal angiographic complications, and a low adverse event rate. Direct comparisons with the standard of care are needed in larger studies to establish clinical utility and superiority.
Abstract 16281: Right Ventricular Systolic Strain Normal Ranges and Comparisons by Contemporary Vendor-Neutral Echocardiography Software: A Prospective Healthy Cohort Study
Authors: Tom Kai Ming Wang, Ankit Agrawal, Tiffany Dong, Aro Daniela Arockiam, Joseph El Dahdah, Muhammad Majid, Elio Haroun, L L Rodriguez, Richard A Grimm, Brian P Griffin, Zoran B Popovic
Journal: Circulation (2023)

Background: Right ventricle longitudinal strain (global: RVGLS and free-wall: RVFWLS) by speckle-tracking echocardiography is increasingly utilized to assess right ventricle systolic function with prognostic value demonstrated in several cardiovascular conditions. Contemporary strain software have addressed past limitations to be able to analyze scans from different vendor scanners, however few studies have validated them externally. We prospectively evaluated the reference ranges and correlations of RVGLS and RVFWLS by the latest strain software in healthy patients. Methods: We prospectively studied 100 healthy subjects undergoing echocardiography during January-April 2023 at our institution, 20 each in age groups 18-29, 30-39, 40-49, 50-59, 60+ years; half were men and half women; and half with GE and half with Philips scans. RVGLS and RVFWLS were quantified using TomTec version 51.02 (Autostrain RV), EchoPAC version 206 (AFI-RV) and VVI software for comparative analyses Results: RVGLS and RVFWLS means (lower limits of normal LLN defined as 95 th percentile)±standard errors were -20.6%±0.3% (-16.9±0.5%) and -24.1±0.4% (-18.6±0.6%) by TomTec; -17.1±0.3% (-14.0±0.5%) and -19.6±0.4% (-15.8±0.7%) by EchoPAC; and -17.3±0.3% (-12.5±0.6%) and -19.2±0.4% (-13.6±0.8%) by VVI respectively, with significant differences between mean RVGLS and RVFWLS of TomTec and EchoPAC or TomTEC and VVI only (P&lt;0.001). Factors with beta-coefficients and 95%CI significantly associated with RVGLS in multivariable linear regression analyses were male sex 1.35 (0.18-2.53) for TomTec; age (per 1 year) 0.06 (0.01-0.10), Philips versus GE scan 1.38 (0.17-2.58) for EchoPAC and 1.54 (0.31-2.78) for VVI. Factors with beta-coefficients and 95%CI significantly associated with RVFWLS in multivariable linear regression analyses were Philips versus GE scan 2.11 (0.67-3.56) for EchoPAC and 2.07 (0.38-3.76) for VVI, and none for TomTec. Conclusion: RVGLS and RVFWLS measurements were feasible for all strain software on both GE and Philips scans, with means and LLN identified. Factors associated with RV strain values varied by strain software, in particular, Philips scans had less negative RVGLS and RVFWLS than GE scans when measured using EchoPAC and VVI but not TomTec.
Abstract 16856: The Upside Down: A Case of Reverse McConnell’s Sign in Mixed Shock and ARDS
Authors: Brett Curtis, Albert Ha, Jeffrey Xie, Adam S Helms, John Howe, Robert Hyzy
Journal: Circulation (2023)

Introduction: We present a case of reverse McConnell’s sign in shock and respiratory failure. Hospital Course: A 48-year-old woman with cirrhosis presented to the emergency department with hypoxia, hypotension, and tachycardia. She endorsed lower extremity edema and orthopnea. Labs noted elevated BNP, procalcitonin, troponin, and lactate. Urinalysis showed signs of infection. EKG did not reveal ischemic changes. CT pulmonary embolism (PE) protocol was negative for PE but showed pulmonary edema. Parasternal short axis views on bedside ultrasound revealed interventricular septal flattening during systole consistent with right ventricular pressure overload ("D sign"). She received broad-spectrum antibiotics for E. coli bacteremia. Trans-thoracic echocardiogram showed a hyperdynamic LV and decreased RV function with a "reverse McConnell sign (rMS)" (figure 1). Providers initiated diuresis once her vasopressor requirement stabilized. She was soon extubated and her oxygen requirement continued to improve with diuresis. Vasopressors weaned in several days. Prior to discharge, trans-thoracic echocardiogram echo showed recovery of RV function. Discussion: This case of respiratory failure and shock highlights the value of prompt echocardiography. Her rMS was likely caused by increased pulmonary arterial pressure from hypoxic vasoconstriction and V/Q mismatch from ARDS. Other heart failure processes seem unlikely. rMS refers to right apical hypokinesis and basal hyperkinesis, inverted compared to its counterpart. Cases are associated with PE and Takotsubo cardiomyopathy, but rMS likely more generally indicates right heart strain. Evidence suggests that rMS may be associated with higher rates of comorbidities and adverse events. Finally, it may represent the RV’s protective mechanism for abruptly increased afterload. Conclusion: Providers should consider rMS as a sign of RV strain to assist diagnosis and management of undifferentiated shock.
Abstract 16984: A Wearable Device Reproducibly Identifies Premature Ventricular Contractions and Tachyarrhythmias in Heart Failure Patients
Authors: Letizia R Romano, Antonio Curcio, Giuseppe Scalzi, Miriam Festa, Biagio Malizia, Alessandra Panarello, Anna Bartone, Sergio Serafino, Francesco Passafaro, Ciro Indolfi
Journal: Circulation (2023)

Introduction: occurrence of ventricular arrhythmias (VAs) has a dramatic impact on prognosis of patients with heart failure (HF). Hypothesis: wearable devices, including smartwatch (SW), might provide real-time informations in patients at risk of VAs. Aims: we therefore evaluated if SW detection of QRS interval width and voltage could reproducibly detect VAs and/or premature ventricular contractions (PVCs) in HF patients. Methods: HF patients (N=100) underwent continuous electrocardiographic (ECG) recordings through telemetry and SW during hospital admission. Left ventricular ejection fraction (EF) and laboratory pro-BNP levels assessments were obtained as well. Correlation of the ECG results was addressed using Pearson’s analysis for normally distributed data and Spearman’s analysis for non-parametric data. Bland-Altman was used for reliability between telemetry and SW ECG measurements. Results: mean EF was 45.92±12.12%; mean pro-BNP was 2826±5823 pg/mL. Using the SW and the ECG data, QRS width and voltage correlation coefficients were 0.990 (p&lt;0.001) and 0.974 (p&lt;0.001), respectively. Concordance was found between the two assessments for QRS width (bias, 0.20; SD 3.0; lower limit, –5.68; upper limit, 6.08), and voltage (bias, -0.029; SD, 0.611; lower limit, –1.227; upper limit, 1.169). Moreover, we found correlation coefficients of 0.964 (p&lt;0.001) and 0.970 (p&lt;0.001), respectively, for PVCs width and PVCs voltage using SW and telemetry or other ECG report. Similarly, both techniques showed positive concordance for PVCs width (bias, 0.368; SD, 2.65; lower limit, -4.83; upper limit, 5.56) and PVCs voltage (bias, 0.54; SD, 1.25; lower limit, -1.91; and upper limit, 2.996). Remarkably, VAs identification by the SW was reproducible and standardized. Conclusions: continuous monitoring through SW might be considered in HF patients upon discharge.
Abstract 18803: Extended Duration Impella Support: A Review of 107 Patients Successfully Supported With Impella 5.5 Device at a Single Institution
Authors: joyce Wald, Alyson Brown, Andrea Jackson, Kathryn Gray, Marisa Cevasco
Journal: Circulation (2023)

Introduction: Impella 5.5 is an FDA-approved microaxial, continuous flow pump intended to provide left ventricular hemodynamic support for 14 days. We report 107 consecutive patients supported with this device, many for extended durations. Methods: The outcomes of consecutive patients supported with Impella 5.5 at an academic hospital from March 2021 to June 2023 are included. Results: 107 patients required 112 Impella 5.5 devices. The majority of patients had a heart failure etiology of NICMP (57, 53%), followed by ICMP (36, 34%), post cardiotomy shock (6, 5%), other (4, 4%), planned post cardiotomy cardiac protection (3, 3%), and congenital heart disease (1, 1%). 60 patients (56%) were SCAI D, 30 patients (28%) SCAI E, and 17 patients (16%) were SCAI C. The majority patients (70,65%) were Intermacs 2. The majority of Impella 5.5 devices were placed as a bridge to decision (55 patients, 51%), followed by BTT (28 patients, 26%), BTR (16 patients, 15%), Bridge to LVAD (7 patients, 7%), and one patient (1%) device was placed for post cardiotomy cardiac protection. 11 patients required interval escalation to concomitant VA-ECMO. Patients requiring ECPELLA were placed on PVA ECMO after an average of 22 days of impella support, and average time of support on ECPELLA was 5.4 days. All patients transitioned to cardiac replacement therapy. Among patients with explant data, 43 supported for &lt; 2 weeks, 38 for 2-4 weeks, and 17 for &gt; 4 weeks. Longest duration of support was 92 days. Of patients reaching a primary endpoint, 42 were transplanted (39%), 21 patients died (20%), 18 patients received durable VAD (17%), 12 were discharged without transplant or VAD (11%), 10 were transferred while on support (9%) and 4 patients are still supported (4%). With respect to complications, 5 patients suffered from strokes, 3 pump thrombosis, 2 had fiber optic cable malfunctions, 2 had purge line leaks, and there were 3 patients with a broken optical sensor, and 2 arterial (brachial and axillary) thrombus. Conclusion: The Impella 5.5 device is a left ventricular support device placed most frequently to successfully stabilize patients undergoing evaluation for advanced therapies who were failing despite inotropic therapy.