tbuckley/cabot-search huggingface dataset:
Abstract 17454: Development and Validation of an Artificial Intelligence 12-Lead Electrocardiogram-Based Mutation Detector for Congenital Long QT Syndrome
Authors: Johan M Bos, Kan Liu, Zachi Attia, Peter A Noseworthy, Paul Friedman, Michael J Ackerman
Journal: Circulation (2023)

Introduction: Over 100 FDA-approved medications, electrolyte perturbations, and many disease states can prolong the QT interval in up to 10% of patients. In contrast, approximately 1 in 2,000 people have congenital long QT syndrome (LQTS) hallmarked by pathological QT prolongation secondary to LQTS-causative mutations. Hypothesis: an artificial intelligence (AI) deep neural network (DNN) analysis of the 12-lead ECG can distinguish patients with LQTS from those with acquired QT prolongation. Methods: The study cohort included 1599 patients with genetically confirmed LQTS and over 2.5 million controls from Mayo Clinic’s ECG data vault. Every patient/control with ≥ 1 ECG above age- and sex- specific 99 th percentile values for QTc [&gt; 460 ms for all patients (male/female) &lt; 13 years of age, or &gt; 470 ms for men and &gt; 480 ms for women above this age] was included. An AI-DNN involving a multi-layer convolutional neural network was developed. To simulate screening conditions, patients were matched at a ratio of 1:2,000 (incidence of LQTS) or 1:200 (balance of LQTS vs acquired QT prolongation in a tertiary referral center). Results: Among the 1,599 patients with LQTS, 808 (&gt; 50%) had ≥ 1 ECG with QTc above the aforementioned QTc thresholds (2,987 ECGs) compared to 361,069/2.5M controls (14% of Mayo Clinic patients getting an ECG, 989,313 ECGs). Following age- and sex- matching and splitting, the model successfully distinguished LQTS from those with acquired QT prolongation at 1:2,000 matching with an AUC of 0.937 (accuracy 89%, sensitivity 81%, specificity 90%, PPV 0.05, NPV 0.99). Furthermore, when matching at a rate that genetically-mediated QT prolongation would be encountered in clinic (1:200), the model still successfully separated the two groups (AUC 0.912, accuracy 88%, sensitivity 78%, specificity 89%, PPV 0.1, NPV 0.99). Conclusion: For patients with a QTc exceeding its 99 th percentile values seen in health, this novel AI-DNN 12-lead ECG distinguishes abnormal QT prolongation stemming from LQTS versus acquired QT prolongation with high performance characteristics (AUC &gt; 0.93). Even when scaled to referral center and LQTS incidence ratios, a negative AI-DNN signal rules out the presence of a LQTS disease-causative mutation with 99% negative predictive value.
Abstract 15373: Guiding Modalities for Non-Culprit Artery Revascularization in Acute Myocardial Infarction With Multivessel Disease: A Pooled Analysis of FLOWER-MI and FRAME-AMI
Authors: Thanakit Suebsaicharoen, Wiphut Dejprasert, Pawin Numthavaj, Amarit Tansawet, Thinnakrit Sasiprapha, Ammarin Thakkinstian
Journal: Circulation (2023)

Background: Currently, it is not yet clear whether angiography or fractional flow reserve (FFR) is better in guiding percutaneous coronary intervention (PCI) for non-culprit artery revascularization in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) after primary PCI. Therefore, a pooled analysis is conducted to summarize the findings from two only available trials, i.e., FRAME-AMI and FLOWER-MI. Aim: To compare major cardiac adverse event (MACE) between angiography-guided and FFR-guided non-culprit artery revascularization in AMI and MVD Method: MACE defined as a primary endpoint of all-cause death, non-fatal myocardial infarction, or unplanned revascularization was the primary outcome while all-cause death was the secondary outcome. Pooled cumulative probability of developing the primary endpoint curves were constructed from extracted Kaplan-Meier curves using Weibull distribution, and a meta-analysis was performed to pool extracted hazard ratio (HR) and 95% confidence intervals (CI). Furthermore, a subgroup analysis of STEMI and NSTEMI groups was performed. Result: Cumulative probability curve is displayed in Figure 1A. A pooled analysis showed no difference between two guiding modalities both in MACE and all-cause death risk reduction. FFR-guided PCI reduced MACE risk by 24% (HR 0.76, 95% CI 0.25-2.27) and risk of all-cause death by 47% (HR 0.53, 95% CI 0.18-1.54) compared to angiography-guided PCI but not statistically significant as shown in Figure 1B. Regarding subgroup analysis concerning MACE, FFR-guided PCI was not superior to angiography-guided PCI in STEMI (HR 1.06, 95% CI 0.60-1.90) despite significantly superior to angiography-guided PCI in FRAME-AMI NSTEMI group. Conclusion: FFR-guided PCI is not superior to angiography-guided PCI in non-culprit artery revascularization in AMI and MVD concerning risk reduction of MACE and all-cause death, but might show superiority in the NSTEMI subgroup.
Abstract 14291: Novel 4D Procrustes Motion Analysis Applied to CMR Links <i>LMNA</i> Mutation Severity With Myocardial Dynamics
Authors: Constantin-Cristian Topriceanu, Mashael Al-Farih, George Joy, Fiona Chan, Matthew Webber, Denis C. Ilie-Ablachim, Hunain Shiwani, Stephen Pettit, Ben O'Brien, Sandesh Choapde, Aaron Hingorani, Alun Hughes, Saidi Mohiddin, Konstantinos Savvatis, William E Moody, Richard P Steeds, James C Moon, Paolo Emilio Puddu, Andrea Barison, Paolo Piras, Gabriella Captur
Journal: Circulation (2023)

Introduction: Procrustes motion analysis (PMA) is a novel method to extract microstructural tensor data from CMR cines. Aim: To illustrate its usefulness in phenotyping patients with confirmed pathogenic lamin ( LMNA ) mutations ( LMNA+). Methods: This n=187 prospective multi-centre CMR study (NCT03860454) recruited LMNA+ (n=67), participants with dilated cardiomyopathy carrying wild-type LMNA gene (DCMwt; n=73) and healthy volunteers (HV, n=47). Left ventricular (LV) cines were analyzed using 3D feature tracking. Generalized procrustes analysis was used to calculate the radial, circumferential, and longitudinal strains. To explore differences in myocardial dynamics between these groups, PMA was employed to derive the procrustes trajectory size at 16 homologous time points of the cardiac cycle in comparison to a common diastolic reference point. Results: Compared to HV, LMNA+ had worse radial and circumferential strain values ( Fig. 1 ). Compared to DCMwt, LMNA + had better strain profiles after adjusting for late gadolinium enhancement. LMNA+ truncating variant carriers had a smaller procrustes trajectory size during diastole compared to splice and missense variant carriers (i.e., reduced myocardial dynamics according to the PMA) ( Fig. 2A ). Similarly, LMNA+ who had a mutation upstream of nuclear localization signal (worse mutation) had lower myocardial dynamics compared to those who had a downstream mutation ( Fig. 2B ). Conclusion: Detailed information on myocardial deformation patterns between diastole and systole can be inferred using PMA applied to CMR cines. Procrustes trajectory size may be a novel marker of myocardial dynamics linked to mutation severity.
Abstract 12786: Predictors of Intermediate to Long-Term Ventricular Pacing Requirement Following Transcatheter Aortic Valve Replacement
Authors: Emerald Feng, Anil Gehi, Anthony Mazzella, John Vavalle
Journal: Circulation (2023)

Objectives: To identify factors associated with persistent atrioventricular (AV) block in patients with permanent pacemaker (PPM) in the peri-transcatheter aortic valve replacement (TAVR) setting. Background: Patients undergoing TAVR may develop AV block requiring pacing. However, whether there are patients who recover AV conduction over time is unknown. Methods: Patients who underwent TAVR and either had pre-existing PPM implanted for sinus node dysfunction or required PPM implantation during the peri-procedural TAVR period were identified from two hospitals in the University of North Carolina Health system. Demographic, electrocardiographic, echocardiographic, and procedural characteristics were abstracted. PPM data was abstracted from remote and in-person PPM interrogations at intermediate (1-12 mo) and long-term (&gt;12 mo) checks. Patients were separated into cohorts with negligible (&lt;1%) or significant (&gt;1%) ventricular pacing burdens. Bivariable and multivariable analyses were performed to identify factors associated with a significant ventricular pacing requirement. Results: The cohort consisted of 159 patients with PPM implanted prior to (n=38) or in the peri-procedural (n=121) TAVR period. Bivariate analyses identified pre-procedural RBBB (17.1% vs 42.9%, p=0.007) and post-procedural RBBB (15.2% and 39.3%, p=0.015) with significant ventricular pacing requirement in the intermediate or long-term period after TAVR. In multivariate analyses, atrial fibrillation (AF) (OR 5, 95% CI 1.78-16.6, p=0.003) and RBBB (OR 11, 95% CI 2.2-100.0, p=.008) in the post-TAVR period were associated with significant ventricular pacing requirements. Patients without AF or RBBB less often required significant ventricular pacing in the intermediate (19.3% vs 80.7%) or long-term periods (19.8% vs 80.2%) after TAVR. Conclusions: Post-procedure RBBB or a history of AF predict long-term persistence of AV block post-TAVR. However, patients without RBBB or AF less often require long-term ventricular pacing and may be candidates for temporary or more basic pacing options (e.g. leadless ventricular devices) as necessary in the peri-op period.
Abstract 12622: Long Term Use of Adaptive Servo Ventilation Improves and Maintains Cardiac Function in Patients With Heart Failure With Central Sleep Apnea and Prevents Readmission Due to Worsening Heart Failure Compared to Short Term Use
Authors: Tatsunori Ikeda, Hisayoshi Murai, Manabu Fujimoto, Tadayuki Hirai, Soichiro Usui, Masayuki Takamura, Keiko Ikeda, Kazuyasu Okeie
Journal: Circulation (2023)

Introduction: Central sleep apnea (CSA) is closely associated with poor prognosis in heart failure (HF) patients. Adaptive servo-ventilation (ASV) was expected as a new treatment for HF patients with CSA. However, the efficacy of ASV is controversial, especially the efficacy of long-term use has remained unclear. Methods: We retrospectively examined all HF patients with CSA treated with ASV seen between May 2008 and November 2022 in our hospital who had not been admitted to the hospital due to worsening HF in the 6 months before initiating ASV therapy. We divided them into 2 groups: (A) non-continues-ASV-treated patients; (B) continues-ASV-treated patients. The outcome was a composite of readmission due to worsening HF and all-cause mortality. Results: During a median follow-up of 10.3 years after leaving the hospital, 11 patients died out of 101 patients. Twenty-two patients (group A) could not continue to use ASV because of its discomfort. Seventy-nine patients (group B) could continue to use the ASV device at night after leaving the hospital over a long period. There were almost no significant differences in the baseline characteristics between the two groups. In group B, during 6-, 12-, and 24-month observations, left ventricular ejection fraction (46.4 +/- 17.9 to 47.1 +/- 15.6, 49.8 +/- 15.8, and 48.2+/- 18.9%, p&lt;0.05 compared with baseline) and brain natriuretic peptide (685.5 +/- 1087.2 to 233.1+/- 362.9, 391.8 +/- 929.0 and 166.9 +/- 195.1 pg/ml, p&lt;0.05 compared with baseline) improved significantly. And there was significantly less readmission by worsening HF than in group A (log-rank P&lt;0.001). However, there were no significant differences in all-cause mortality between the two groups (log-rank P=0.221). Conclusions: This study showed that long-term ASV therapy for more than 10 years reduced readmission by worsening HF with CSA patients compared to short-term use due to improved and maintained cardiac function but did not affect mortality.
Abstract 16250: Latent His-Purkinje Disease Unmasked by Beta Blocker Overdose
Authors: Gabriela Narowska, Joshua M Cooper, Anuj Basil
Journal: Circulation (2023)

Background Symptomatic bradycardia usually has a single mechanism and treatment modality. Identifying the culprit mechanism can be challenging, especially when faced with concurrent pathologies. We present a case of severe symptomatic bradycardia where appropriate management of one mechanism unmasked a second mechanism, with a need for pacemaker placement. Case Presentation A 56-year-old patient presented with beta blocker overdose and severe bradycardia. The initial ECG showed sinus bradycardia with a sinus cycle length of 2060ms and 2:1 AV conduction, with each conducted P wave preceded by a long-coupled junctional escape beat. Atropine resulted in shortening of the junctional escape interval but had no effect on the sinus rate. There was now 1:1 AV conduction, with each P wave being preceded by a faster junctional escape beat. Glucagon resulted in acceleration of the sinus rate to a cycle length of ~820ms (73 bpm) with return of 1:1 AV conduction, a PR interval of 200ms, and no junctional beats. Conducted beats showed a right bundle branch block and left axis deviation. The dependence of AV conduction on a preceding QRS complex within a certain window of time highly suggested infranodal conduction disease manifesting as phase 4 AV block. While normal sinus rates and 1:1 AV conduction were restored with glucagon, the presence of infranodal disease warranted dual chamber pacemaker implantation. In follow-up, with atrial pacing support, there was &lt; 1% ventricular pacing. Discussion Two causes of bradycardia were simultaneously present - sinus bradycardia due to beta blocker overdose, and 2nd degree AV block due to His-Purkinje disease. Phase 4 AV block is a mechanism of paroxysmal AV block (PAVB) in patients with diseased His-Purkinje system. Spontaneous depolarization occurs in diseased fibers during prolonged periods of ventricular pause, such as with slowing of the sinus rate. The sodium channels are blocked during phase 4 of the action potential and therefore the conduction system is incapable of depolarizing due to low resting membrane potentials. In this case, AV 1:1 conduction can only be restored with a premature ventricular contraction. This is an overall under-recognized entity and should be managed with pacemaker implantation.
Abstract 14532: The Off-Hour Effect on Clinical Outcomes of ST-Segment Elevation Myocardial Infarction Complicated by Cardiogenic Shock Patients Treated With Impella: Insight From Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD)
Authors: Takahiro Suzuki, Taku Asano, Daisuke Yoneoka, Yasufumi Kijima, Atsushi Mizuno
Journal: Circulation (2023)

Introduction: The off-hours effect is a contentious issue in that patients admitted on weekends or nighttime have worse outcomes than on weekday daytime. The off-hours effect in patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMI-CS) treated with Impella has not been fully evaluated. Hypothesis: The off-hours admission is associated with longer door-to-unload (DTU) time, door-to-balloon (DTB) time, and higher mortality in this population. Methods: We used the Japanese large-scale registry data for Percutaneous Ventricular Assist Device (J-PVAD), which registered all consecutive patients treated with Impella from December 2019 to July 2022. We compared the effects of on-hours and off-hours admissions on DTU time, DTB time, and 30-day mortality. We defined “on-hours” as between 8:00 and 19:59 on weekdays and the other time as “off-hours”. A multiple linear regression model was used to reveal the independent factors of prolonged DTU and DTB times. The Cox proportional hazards model was applied to calculate adjusted hazard ratios [aHR] for 30-day mortality, controlling for conventional cardiac risk factors. Results: Of 2,453 patients, 775 (32%) (mean age 68 years, 628 (81%) male) STEMI-CS patients treated with Impella were included. Among them, 401 (39%) were admitted during off-hours. We observed 155 deaths (49%) among patients admitted off-hours and 134 deaths (36%) among patients admitted on-hours during the follow-up period (median: 23 days). The DTU and DTB times were significantly longer in patients admitted off-hours than in patients admitted on-hours (91 (IQR 74-164) vs. 74 (62-151) minutes, p&amp;lt;0.001; 104 (77-134) vs. 89 (61-122), p&amp;lt;0.001, respectively). The linear regression model showed that the off-hours admission was associated with longer DTU time (β=14.3 minutes, 95% CI 4.8-23.8, p=0.003) and DTB time (15.4, 5.0-25.7, p=0.004). The Cox proportional hazards model showed that off-hours admission was associated with a higher risk of 30-day mortality than on-hours admission (aHR=1.42, 95% CI: 1.03-1.96, p=0.03). Conclusion: Our findings implied that the off-hours effect existed in DTU time, DTB time, and 30-day mortality among STEMI-CS patients treated with Impella.
Abstract 15399: Cardiac Sympathetic Nerve Activity in Women With a History of Takotsubo Syndrome: A Novel Stress Myocardial Radionuclide Imaging Strategy
Authors: Joseph T Chang, Puja K Mehta, Michael D Nelson, Jenna Maughan, Marie Lauzon, Sean W Hayes, John D Friedman, Daniel S Berman, C Noel Bairey Merz, Janet Wei
Journal: Circulation (2023)

Introduction: Takotsubo syndrome (TTS) is characterized by transient left ventricular (LV) systolic dysfunction, triggered by physical or emotional stress, and associated with increased long-term cardiovascular morbidity. Cardiac iodine-123-meta-iodobenzylguanidine (mIBG) imaging has previously demonstrated sympathetic hyperactivity in the TTS subacute state which improves at follow-up during rest imaging. Cardiac neuronal dysfunction in response to stress has not been evaluated in recovered TTS. Hypothesis: Sympathetic hyperactivity, as measured by stress mIBG, is abnormal in TTS after recovery of LV ejection fraction (LVEF). Methods: To elicit a sympathetic challenge, women with history of TTS with recovered LVEF (n=19) and asymptomatic age- and sex-matched reference controls (n=10) underwent treadmill (6 minutes) with simultaneous mental-stress testing (public speaking with anger recall). mIBG (10 mCi) was injected during exercise, and planar and SPECT imaging were performed at 15 min (early) and 240 min (late), followed by Tc-99m tetrofosmin myocardial perfusion imaging. Early and late heart-to-mediastinal ratio (HMR) and washout rate (WR) corrected for background were calculated. Results: Median time from last TTS event was 23 months (range 4-56). Overall mean age was 60± 12 years, body mass index 25 ± 4kg/m 2 , resting LVEF 70 ± 7%, 41% hypertension and 0% diabetes with no difference between TTS and controls. TTS had higher resting (140 ± 22 vs 123 ± 19 mmHg, p=0.049) and peak (187 ± 17 vs 171 ± 15 mmHg, p= 0.018) systolic blood pressure. While the early HMR and WR were similar, the late HMR was significantly lower in the TTS group (Figure). Conclusions: Women with a history of TTS have lower late HMR but similar WR, suggesting neuronal dysfunction in response to sympathetic challenge persists long after recovery from TTS event. Further analysis of catecholamine levels and central nervous system neural pathways will explore the mechanism of dysregulation.
Abstract 12495: Modes of In-Hospital Death in Patients With Cardiogenic Shock (CS): An Analysis From the Critical Care Cardiology Trials Network (CCCTN)
Authors: Sachit Singal, Fadel Bofarrag, Erin A Bohula, Vivian Baird-Zars, Jason N Katz, Sean Van Diepen, David Morrow, David Berg
Journal: Circulation (2023)

Introduction: Mortality from cardiogenic shock (CS), a syndrome of multi-organ system dysfunction, remains high. However, data regarding how patients with CS expire are limited and may have implications for designing clinical trials, identifying therapeutic strategies, and improving outcomes. Aim: We sought to describe primary modes of in-hospital death among patients admitted with CS to cardiac intensive care units (CICUs). Methods: CCCTN is a multi-national research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Using standardized definitions, site investigators classified the direct mode of in-hospital death for patients with CS. Categories included 8 possible modes of cardiovascular (CV) and non-CV death ( Fig ). Subgroups defined by cardiac arrest prior to CICU admission and use of mechanical circulatory support (MCS) were explored. Results: Among 1098 CS cases captured from 10/2021-09/2022, 358 (32.6%) died during the index hospitalization with a median time to death of 4.3 (Q1-Q3, 1.1-10.9) days from CICU admission. Among the deaths, 50%, 41%, and 9% occurred in the context of HF-CS, AMI-CS, and secondary CS, respectively. Overall, mode of death was CV in 82% of cases ( Fig A ). Refractory CS was the dominant mode of death (66%), followed by arrhythmia (13%), anoxic brain injury (6%), and respiratory failure (5%; Fig A ). Compared to patients without preceding cardiac arrest, those with cardiac arrest prior to CICU admission were more likely to die from anoxic brain injury (10% vs. 1%; p&lt;0.01; Fig B ). Compared to patients managed without MCS, those with MCS were more likely to die from refractory shock (p&lt;0.01), either cardiogenic (74% vs. 61%) or non-cardiogenic (6% vs. 3%; Fig C ). Conclusions: Most in-hospital deaths in patients with CS are related to direct CV causes, particularly refractory CS. However, there is potentially important heterogeneity in mode of death across subgroups defined by preceding cardiac arrest and use of MCS.
Abstract 13543: Novel Genes That Regulate QT Interval in Taiwanese Cohort
Authors: Jien-jiun Chen, Chia-Ti Tsai
Journal: Circulation (2023)

Introduction: QT interval denoted repolarization of the ventricule. QT intervals prolongation or shortening would lead patients prone to sudden cardiac death, i.e. Long QT or Short QT syndrome. There are many genes that have been reported to be related to QT interval changes. In this study, we used Genome wide association study(GWAS) to search for genes that regulate QT interval in a large Taiwanese cohort. Methods: We collected 13020 samples and did GWAS study. We collect ECG and analyze QTc interval by standard method. We search for genes and SNP have correlation with QT interval and used Taiwan Biobank as control. The QTc was measured as continuous variables. A P&lt;10 -8 was considered significant variants. Results: In this study, we found many variants that regulate QT interval. (Figure 1). The variants included rs36092684 encoding C1orf132 which was long none coding RNA (never reported before), rs846111 that influences QT interval, 1:162021296:A:ATTG (a novel variants non reported yet), rs12143965, encoding NME7 ( ATP1B1 was a strong functional candidate, although NME7 could not be excluded without functional validation), rs10490255 encoding SLC8A1 Na + -Ca ++ exchanger that wound prolonged QT, rs16862199, encoded SLC19A2 genes that was associated with Thiamine-responsive megaloblastic anemia (TRMA), in such patients, their QT prolonged, rs2277923, encoding NKS2-5 that would cause dilated cardiomyopathy, conduction disorder, long QT, tetralogy of Fallot, rs144500919 (a novel SNP), rs12665409 encoding SLC35F1 that affects QT interval, and rs3778873(KCNH2), rs2074239 (KCNQ1). Conclusion: In this large Taiwanese QT study, we identified variants that would regulate QT interval. Some were reported before, such in QTGEN or QTSCD studies, and others were novel. The novel variants warrant further functional studies.