Circulation, Ahead of Print. Background: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients.Methods: In an international cohort study with 20 centers, phenotype-positive children with primary HCM
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Abstract 15241: Mixed Meal Tolerance Test Elicits Distinct Metabolite Kinetics for Individuals With and Without Diabetes
Circulation, Volume 146, Issue Suppl_1, Page A15241-A15241, November 8, 2022. Introduction:Branched chain amino acids (BCAA) are strongly associated with incident diabetes and CVD, and drugs that target their metabolism, especially in the context of a meal, are emerging treatments for diabetes given supportive genetic data. However, little is known about how BCAA, their breakdown metabolites—branched chain ketoacids (BCKA), and other metabolites change after a meal.Hypothesis:BCAA and BCKA levels are higher in individuals with diabetes after a mixed meal tolerance test (MMTT) than in those without diabetes, and a MMTT will uncover additional metabolites involved in dysregulated metabolic pathways secondary to diabetes.Methods:We administered a MMTT to 13 adults with diabetes treated by metformin alone and 11 age and sex matched controls. We measured BCKA, BCAA, and 194 metabolites at 8 timepoints across 6 hours. We used a mixed model for repeated measurements to compare between group differences at each timepoint with adjustment for baseline levels.Results:Across the participants (57 ± 8 years, 71% female, BMI 28 ± 4 kg/m2), adjusted BCAA levels were similar at all timepoints between groups, but adjusted BCKA levels were higher in those with diabetes at 120 minutes (Figure). An additional 9 metabolites had 4 or more timepoints with significant between group differences (Figure). Acylcarnitine, palmitic acid, and linoleic acid showed slower rates of decrease and recovery in those with diabetes, altogether supportive of impaired fatty acid uptake and oxidation. Glycocholic acid showed no increase in those with diabetes, a finding that requires further study given growing recognition of bile acids’ paracrine effects on the liver.Conclusions:In contrast to BCAA, BCKA remained elevated after a MMTT in those with diabetes, suggesting that BCKA catabolism may be a key dysregulated process in the link between BCAA and diabetes. Other metabolites with different kinetics after a MMTT may be markers of dysmetabolism and impaired nutrient handling.
Abstract 12029: The Impact of the Myocardial Bridge on Coronary Functional Test in Patients With Ischemia With Non-Obstructive Coronary Arteries
Circulation, Volume 146, Issue Suppl_1, Page A12029-A12029, November 8, 2022. Introduction:The possibility of myocardial bridge (MB) causing chest pain has been widely reported; however, the effect of MBs on coronary microvessels has not been thoroughly investigated.Hypothesis:Thus, this study evaluated the effects of MB on epicardial coronary artery and coronary microvascular function during coronary angiography (CAG) and coronary function tests (CFT) in patients with ischemia with non-obstructive coronary arteries (INOCA).Methods:This study included 57 patients with INOCA who underwent CAG and CFT to evaluate chest pain. In CFT, acetylcholine was first administered intracoronarily in a stepwise manner, followed by chest symptoms, electrocardiographic changes [Editor1] and CAG. Positive coronary spasm was defined as coronary vasoconstriction of >90% on CAG accompanied by chest symptoms or electrocardiographic ST-T changes. After nitroglycerin administration, CAG was performed to assess MB, which is defined as the systolic narrowing of the coronary artery diameter by >20% compared to that in diastole. Coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were subsequently obtained by transvenous adenosine triphosphate infusion using a pressure wire. Coronary microvascular vasodilatory dysfunction (CMD) was defined as CFR of
Abstract 11615: The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy
Circulation, Volume 146, Issue Suppl_1, Page A11615-A11615, November 8, 2022. Introduction:Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test (EST) is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients.Methods:: In an international cohort study with 20 centers (PRIMaCY), children
Abstract 12737: Baseline Carotid Sinus Massage in the Supine Position Predicts Outcome of Head Up Tilt Table Testing: Potential for Abbreviating the Tilt Table Test Protocol
Circulation, Volume 146, Issue Suppl_1, Page A12737-A12737, November 8, 2022. Introduction:Carotid sinus massage (CSM) has been used to evaluate carotid sinus hypersensitivity. Its role in evaluating a vasodepressor response has not been well studied. CSM can also result in a vasodepressor response in the absence of significant bradycardia. Its role in predicting the subsequent outcome of head-up tilt testing (HUT) is not well defined.Hypothesis:A vasodepressor response elicited with baseline carotid sinus massage (CSM) may predict the subsequent outcome of HUT.Methods:In this prospective study Consecutive patients with a history suggestive of a reflex neurocardiogenic etiology underwent HUT. Patients underwent HUT testing using a standard protocol, including baseline CSM in the supine posture followed by HUT testing at 60 degrees for 30 minutes. If negative, a repeat of CSM was performed in the upright posture. Then, isoproterenol was infused in incremental dose 1 to 3 mcg/minute.Results:25 patients (20 females and 5 males) with a mean age of 52.87±6.77 years underwent HUT. 5 out of 25 (20%) patients had a positive tilt result for a vasodepressor response. 4 of these 5 patients had a significant vasodepressor response (symptomatic hypotension BP drop less than 30 mmHg) without significant bradycardia (HR less than 50 BPM) during CSM in the supine posture. Of these patients, 3 patients became positive during HUT and 1 patient became positive during isoproterenol infusion. The positive predictive value was 0.8. Sensitivity was 67%. 20 out of 25 (80%) patients had a negative tilt result for a vasodepressor response despite protocol completion. 18 of these 20 patients had no drop in BP during CSM and no significant bradycardia. The negative predictive value was 0.9. The specificity was 94.74%. 2 of these patients had a negative response on CSM but a borderline response at HUT with borderline symptoms with the isoproterenol. These 2 had a transient drop in BP when CSM was repeated at the end of 30 minutes during the head-up position.Conclusions:In this population of patients, a negative CSM in the supine posture predicted a subsequent negative Tilt test. Baseline CSM can be performed at the bedside and may obviate the need for full tilt table testing even for patients with a clinical diagnosis of reflex syncope (vasodepressor).
Abstract 10285: Prognostic Value of Provocative Spasm Test in Patients With Myocardial Infarction With and Without Obstructive Coronary Arteries
Circulation, Volume 146, Issue Suppl_1, Page A10285-A10285, November 8, 2022. Introduction: Coronary spasm potentially contributes to the pathogenesis of acute myocardial infarction (MI) with obstructive coronary artery disease (MICAD) and particularly warrants close consideration in MI with non-obstructive coronary arteries (MINOCA). However, there are limited data concerning the impact of coronary spasm in acute myocardial infarction (AMI). We aimed to assess the prognostic impact of provocative coronary spasm in both MICAD and MINOCA.Methods:Of 1,101 AMI patients admitted to our hospital from January 2012 to December 2019, 267 AMI patients (MICAD: n=198, MINOCA: n=69) who underwent emergency CAG and invasive provocative spasm test were assessed. The primary endpoint was a composite of major adverse cardiac events (MACE), defined as cardiovascular death, acute coronary syndrome, or revascularization. The median follow-up duration was 48 months.Results:Provocative test was positive in 143 (72.2%) of MICAD group and 33 (47.8%) of MINOCA group. In MICAD group, spasm-positive patients had a significantly higher occurrence of both MACE [27 (18.9%) vs. 4 (7.3%); p=0.0413] and Revascularization [25 (17.5%) vs. 3 (5.5%); p=0.0296] compared to spasm-negative patients. In MINOCA group, MACE occurred only in patients with spasm-positive [4 (12.1%) vs. 0 (0%); p=0.0473]. Among the 4 groups based on the type of MI (MICAD or MINOCA) and the presence of provoked coronary spasm, there was a significant difference in the MACE-free survival rate, with the lowest rate observed for MICAD patients with spasm-positive (log rank P=0.0111). In a Multivariable analysis, provoked coronary spasm was significantly associated with MACE in MICAD group (hazard ratio, 3.37;95% CI, 1.20-12.10; P=0.0189).Conclusions:Provocative spasm test could provide prognostic stratification for AMI patients.
Abstract 14958: Association of Smartwatch-Based Resting Heart Rate With Cardiorespiratory Fitness Measures From Cardiopulmonary Exercise Test in the Community
Circulation, Volume 146, Issue Suppl_1, Page A14958-A14958, November 8, 2022. Introduction:Resting heart rate (HR) is an established predictor of cardiorespiratory fitness. Commercial smartwatches permit remote HR monitoring in real world settings over long periods of time, but the relations of smartwatch measured HR and cardiorespiratory fitness in the general public remain uncharacterized.ObjectiveWe aimed to examine the associations of resting HR measured with a smartwatch in the electronic Framingham Heart Study (eFHS) with multi-dimensional fitness assessment via cardiopulmonary exercise test (CPET). We hypothesized that participants with lower resting HR would have greater cardiorespiratory fitness.Methods:eFHS participants were enrolled at an FHS research exam (2016-2019) and provided with a study smartwatch that collected longitudinal HR data for up to 3 years. We identified participants’ HR measures in the sedentary state through a classification algorithm to calculate the average resting HR for each participant. At the same exam, participants underwent CPET performed on a cycle ergometer. Multivariable linear models were used to test the association of resting HR with CPET indices. We used P
Abstract 9903: Artificial Intelligence Driven Wearable 2-minute Seismocardiography Test for Detection of Aortic Valve Stenosis Severity
Circulation, Volume 146, Issue Suppl_1, Page A9903-A9903, November 8, 2022. Introduction:Standard diagnosis of aortic valve stenosis (AS) requires clinical imaging by echocardiography or cardiac MRI. The purpose of this study was to test the performance of easy to use, artificial intelligent (AI) driven seismocardiogram (SCG) chest acceleration recordings for point of care screening and identification of AS.Hypothesis:SCG measurements can be used by a low dimensional convolutional neural network (CNN) to accurately predict presence or absence of aortic valve stenosis (AS) and severity of dysfunction.Methods:This IRB approved study included 45 controls (age 46±17y, 20 F, no known cardiovascular disease) and 30 aortic valve disease (AVD) patients (age 30±20y, 7 F, 21 bicuspid). A wearable SCG device (integrated ECG/accelerometer microelectronics) was placed for 2min chest acceleration recordings on the same day as standard of care echocardiography or cardiac MRI, which was used as ground truth data to classify valve function (normal: AS-, mild AS: AS+, moderate/severe AS: AS++). A deep learning CNN (2х2 kernel, softmax/cross entropy classification) was configured to predict/detect degree of AS from spectrally decomposed SCG measurements. Randomized 50% split of subjects was used for CNN training/testing. Performance detecting AS was evaluated for classification accuracy.Results:AI driven SCG detection of valve function abnormality had high sensitivity/specificity (90%, 67%) with a net area under curve (AUC) 0.86. Correct classification of the degree of AS was achieved in 76% of subjects. Normal (AS-) vs abnormal function (AS+ or AS++) was accurately identified by AI driven SCG for 86% of subjects.Conclusions:This feasibility study demonstrates that the combination of easily measured 2 minute SCG with a deep processing pipeline could successfully detect the presence and severity of AS, supporting clinical promise for potential use as a low cost, front line screening tool to identify patients with aortic valve dysfunction.
Abstract 14141: A Novel Endothelial Function Test in Predicting Late Coronary In-Stent Restenosis
Circulation, Volume 146, Issue Suppl_1, Page A14141-A14141, November 8, 2022. Introduction:Endothelial dysfunction is related with in-stent restenosis (ISR) of prior drug-eluting stents (DES) implanted more than 1 year ago (late ISR). EndoPAT is a novel non-invasive test quantifying endothelial function as reactive hyperemia peripheral arterial tonometry index (RHI).Hypothesis:EndoPAT is a potential predicting test for late ISR.Methods:We conducted a case control study on 186 patients with coronary DES implanted more than 1 year ago in a single medical center. Those who had contraindications to EndoPAT test, acute myocardial infarction, coronary artery bypass graft (CABG), chronic kidney disease (CKD) stage III and above, active infection and rheumatologic disease or acute decompensated heart failure were excluded. Patients were divided into ISR and non-ISR group based on coronary angiography. EndoPAT test was done at 24 to 48 hours prior to catherization. LnRHI is an index after natural log transformation of RHI. A receiver operative characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of LnRHI for predicting late ISR.Results:ISR group had significantly more patients with history of ISR or triple-vessel disease, longer stent length and fewer totally occlusive lesions than non-ISR group. LnRHI was significantly lower in ISR group than in non-ISR group (0.66 vs 0.50, p
Abstract 11938: Novel Approach for Optimal Assessment of Cardiovascular Risk of Blood Pressure in Asymptomatic Subjects Utilizing Mild Exercise Stress Test Protocol
Circulation, Volume 146, Issue Suppl_1, Page A11938-A11938, November 8, 2022. Background:BP risk class assessment has been relying on resting BP (rBP) measurements by healthcare providers. Often, this measurement does not correlate with 24-hour ambulatory BP monitoring nor with at-home measurements.Purpose:To assess whether abnormal rise in BP post-mild exercise protocol (PMEP), which resembles most of the activities subjects are under all day, will be more physiologic and informative for risk stratification, beyond the rBP measurements.Methods:We screened 2,924 subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System, also known as the Rasmussen Risk Score, which consists of 10 tests: 7 vascular and 3 cardiac (published previously). The vascular tests include rBP, BP PMEP (2.4 mi/hr and 7% elevation for 3 minutes), small (C2) artery stiffness, and CIMT. Out of the total subjects, 1094 (37%) were asymptomatic and on no medications. These were divided into four BP classes according to the current ACC/AHA guidelines.Results:In the table, normotension with an abnormal rise in BP PMEP has significant cardiovascular structural and functional abnormalities (CVSFA) than those without. Also noted, the higher the BP class, the higher the CVSFA with and without an abnormal rise in BP PMEP.Conclusions:Abnormal rise in BP PMEP in normotensive subjects is associated with significant CVSFA. This may represent a “masked hypertension” cohort. These findings mandate early diagnosis, follow-up, and optimal treatment. Additionally, an abnormal rise in BP PMEP in other classes is more pronounced with stepwise increases in BP class. Hence, we advocate for PMEP for BP classification and treatment. Early detect to protect.
Abstract 13568: Characterization of the Maladaptive QTc Response During the Treadmill Exercise Test in Untreated Patients With Long QT Syndrome
Circulation, Volume 146, Issue Suppl_1, Page A13568-A13568, November 8, 2022. Background:Long QT syndrome (LQTS) is a genetic heart disease affecting about 1 in 2000 persons. Around 40% of patients with LQTS can have a nondiagnostic, normal QTc at rest. The treadmill exercise stress test (TEST) can help unmask patients with concealed LQTS with a characteristic maladaptive, paradoxical increase in QTc ( 460 ms) during the recovery phase. In fact, the recovery phase QTc value has been added to the latest diagnostic score for LQTS.Objective:To characterize the TEST-derived QTc profile of untreated patients with LQTS and determine its diagnostic and prognostic utility.Methods:Retrospective analysis was performed on TEST data derived from 249 patients with LQTS (129 LQT1, 64 LQT2 and 56 LQT3) untreated at the time of their TEST compared with 236 controls. The Bazett’s corrected QTc was calculated at rest (sitting, supine, and standing), during exercise at 1 min, 3 mins, and peak exercise, and during recovery phase at 1, 3 and 5 mins.Results:The mean resting QTc was significantly higher in LQTS patients (457 ± 30 ms) compared to controls (420 ± 24 ms; p
Abstract 15379: Syncope and Pre-Syncope on the Exercise Test
Circulation, Volume 146, Issue Suppl_1, Page A15379-A15379, November 8, 2022. Background:Data on the occurrence of syncope and presyncope with hemodynamic instability during graded exercise test (GXT) are limited.Methods:We reviewed the Mayo Integrated Stress Center database for non-imaging GXTs performed between January 2006 and December 2010 and registered syncopic/presyncopic episodes. Electronic medical records were reviewed for clinical information, outcomes, and mortality. SAS was used to provide background statistics.Results:During the study period, a total of 40,715 GXTs were performed on 33,885 unique patients, including 16,306 (40.0%) GXTs on patients with known cardiovascular disease (CVD). High risk for cardiac syncope is defined as prior cardiac arrest/ventricular tachycardia, ischemic cardiomyopathy, implanted defibrillator, history of atrial fibrillation, sotalol, amiodarone, LQTS, HOCM, aortic stenosis was identified in 3263 patients (6.0%), while risk factors for non-cardiac syncope (POTS, history of dizziness/spells/syncope, rest SBP < 100 mmHg, age ≥ 80 years, female age < 30 years, beta blocker use) were found in 15,925 patients (39.1%). Despite the presence of so many patients at risk, only 8 episodes of syncope occurred (0.020% per test; 0.023% per individual patient). Another 5 episodes of near-syncope with documented hypotension were aborted by the quick action of the testing staff (0.012% per test; 0.015% per individual patient). Only 1 patient (a 71yo M with severeCAD) required electrical cardioversion for ventricular fibrillation. None of the other patients, including all 6 women, presented with tachyarrhythmias. There were no deaths and no significant musculoskeletal trauma.Conclusion:Despite many patients with risk factors for cardiac and non-cardiac syncope in the cohort, syncope, and near-syncope with hemodynamic instability were very rare findings on guideline-directed GXTs.
Abstract 14339: Differences in Clinical and Angiographic Characteristics Following Intracoronary Ergnovine and Acetylcholine Provocation Test for Coronary Artery Spasm
Circulation, Volume 146, Issue Suppl_1, Page A14339-A14339, November 8, 2022. Background:Ergnovine (Erg) and Acetylcholine (Ach) are useful agents for assessing significant coronary artery spasm (CAS). However, comparison studies of the two agents are limited.Methods:A total of 8,093 consecutive patients (pts) who underwent Erg or Ach provocation test between November 2004 and June 2021 were enrolled. Significant CAS was defined as focal or diffuse severe transient luminal narrowing ( >70%) with/without chest pain or ST-T change on ECG. We divided into two groups according to provocation agent; 1) the Erg group (n=639), 2) the Ach group (n = 7,454). We investigated whether there are differences in clinical and angiographic characteristics according to intracoronary Erg or Ach provocation test.Results:Baseline clinical characteristics were similar between the two groups except the Erg group were more elderly (58.5 years vs 56.6 years, p < 0.001) and dyslipidemia (36.0% vs 18.6%, p < 0.001) but lower rates of current smokers (16.0% vs 21.1%, p = 0.002) and alcoholics (27.1% vs 32.9%, p = 0.002). During the provocation test, the higher rates of myocardial bridge, ECG change, chest pain, atrioventricular node block, and positive CAS results but lower rates of baseline spastic change were shown in the Ach group. More pts received to lower Ach dose and higher Erg dose during the provocation test. In CAS positive patients, the Ach group had higher rates of spasm in the left anterior descending artery and mid site, but lower proximal site (table).Conclusion:Clinical and angiographic parameters were different between Erg and Ach provocation tests. Further study would be needed to validate the different parameters and different positive rates between the two agents.Table. Angiographic and Procedural Parameters during Ergonovine versus Acetylcholine Provocation Test
Abstract 14078: Exercise Pulmonary Impedance and Coupling Stress Test, and MRI-Based Regional Strain Analysis: Identifying Afterload-Sensitive Phenotypes in PH-HFpEF
Circulation, Volume 146, Issue Suppl_1, Page A14078-A14078, November 8, 2022. Objectives:In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and impaired left ventricular-interventricular septal contributions to RV function (ventricular interdependence; VI).Methods:Subjects (n=13) with early-stage PH (per echo) and NYHA II-III dyspnea were prospectively enrolled. Exclusion criteria: advanced disease with NYHA IV, LVEF