Cardiac Repolarization Abnormalities Research Articles

Cardiac repolarization abnormalities and neurally mediated syncope: overlooked aspects in the diagnosis of pheochromocytoma

BackgroundPheochromocytoma is a rare catecholamine-producing tumour originating from adrenal chromaffin cells. Classic clinical presentation includes headache, diaphoresis and palpitation. Syncope is uncommon and may result from hypotension or arrhythmia. We report a case of neurally mediated syncope in pheochromocytoma associated with cardiac repolarization abnormalities, a unique presentation of the disease.Case presentationThis case report presents a 28 year-old woman, describing recurrent syncope usually preceded by prodromes such as headache, visual blurring, heart palpitations and psychomotor agitation. Firstly she was diagnosed with anxiety and depression, but there was no improvement of symptoms with psychiatric treatment. Previous Holter revealed long QT interval. Echocardiogram showed normal dimensions, preserved left ventricular function and no valvopathies. The patient was referred for a Head-up tilt test (HUTT) in order to investigate reflex syncope. The electrocardiogram (ECG) exhibited normal sinus rhythm and diffuse cardiac repolarisation abnormalities. HUTT was positive for vasodepressor type neurally mediated syncope and ECG showed U waves after a syncope episode. This electrocardiographic finding motivated further clinical investigation. The patient also described abdominal pain, increased abdominal volume, weight loss and blood pressure instability. Based on clinical history and ventricular repolarisation abnormalities uncovered by HUTT, pheochromocytoma was suspected. Urinary test was positive for catecholamines and the abdominal imaging revelead expansive lesion. She underwent surgery to remove the pheochromocytoma, confirmed by immunohistochemistry.ConclusionsAfter surgery she had no recurrency of symptoms, remaining asymptomatic after six years of follow-up, suggesting a cause-effect relationship between neurally mediated syncope and pheochromocytoma.

The Heart of Rett Syndrome: A Quantitative Analysis of Cardiac Repolarization.

Rett syndrome (RTT) is a developmental encephalopathy disorder that is associated with a high incidence of sudden death presumably from cardiorespiratory etiologies. Electrocardiogram (ECG) abnormalities, such as prolonged heart-rate corrected QT (QTc) interval, are markers of cardiac repolarization and are associated with potentially lethal ventricular arrhythmias. This study investigates the cardiac repolarization characteristics of RTT patients, including QTc and T-wave morphology characteristics. A retrospective quantitative analysis on 110 RTT patients and 124 age and sex-matched healthy controls was conducted. RTT patients had longer QTc, more abnormal T-wave morphology, and greater heterogeneity of cardiac repolarization parameters compared to controls. Even RTT patients without prolonged QTc had more abnormal ECG and T-wave characteristics than controls. Among RTT patients, MECP2 patients had prolonged QTc compared to CDKL5 and FOXG1 patients. A subset of five RTT patients who died had normal QTc, but more abnormal T-wave morphology than the remaining RTT patients. Cardiac repolarization abnormalities are present in RTT patients, even without long QTc. T-wave morphology is related to RTT genotype and may be predictive of mortality. These findings could be used to help the management and monitoring of RTT patients.

Abstract 16516: CMR-ECG Imaging in Hypertrophic Cardiomyopathy Detects Electrophysiological Abnormalities Before Hypertrophy or ECG Changes

INTRODUCTION: In hypertrophic cardiomyopathy (HCM), ventricular arrhythmia associates with severity of LVH and scar, and presence vs absence of a sarcomeric gene mutation (G+LVH+ vs G-LVH+). Also, ECG changes in subclinical HCM (G+LVH-) signal increased risk of phenotype progression. HYPOTHESES: ECG Imaging (ECGI) can detect: i) subtle electrophysiological (EP) abnormalities in subclinical HCM (pre-LVH). ii) EP abnormalities related to genetic status (G+ vs G-LVH+) and structural changes (late gadolinium enhancement [LGE], max. wall thickness [MWT]) in overt disease. METHODS: 200 participant multicenter study: 70 G+LVH-, 51 G+LVH+, 53 G-LVH+ and 26 healthy volunteers (HV) underwent 12-lead ECG (to detect abnormal Q-waves, repolarization changes, LVH criteria) and CMR-ECGI computing epicardial unipolar electrograms (UEGs) to derive: activation time (AT), activation-recovery intervals (ARIc), spatial gradients (activation: G AT , repolarisation: G RT ) and fractionation. RESULTS: Compared to HV, G+LVH- had prolongation of AT (40.3±7.3 vs 35.4±6.1 ms p=0.003) and steeper G RT (mean: 1.12±0.27 vs 1.00±0.23 ms/mm p=0.042, max: 11.7±2.8 vs 10.0±1.9 ms/mm p=0.005). AT was prolonged even in G+LVH- with a normal 12-lead ECG (p<0.004). Compared to G+LVH-, G+LVH+ had similar AT but a more prolonged ARIc (275±29 vs 245±26 ms p<0.001). Compared to G-LVH+, G+LVH+ had similar MWT and LGE, but more signal fractionation (0.02±0.02 vs 0.01±0.03% UEGs with ≥2 deflections p=0.002). In overt HCM (all LVH+), MWT associated with AT ( r s 0.25 p=0.011) while LGE burden associated with G AT ( r s=0.27 p=0.006) and fractionation ( r s=0.22 p=0.025). CONCLUSION: Cardiac activation prolongation and repolarization abnormalities occur in subclinical HCM (before hypertrophy). Activation is prolonged even in subclinical HCM with normal 12-lead ECG. In overt HCM, ECGI abnormalities track adverse structural changes and reveal greater fractionation in those with a sarcomeric mutation.

Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting.

In coronary artery bypass grafting (CABG), abnormal cardiac repolarization is associated with adverse cardiovascular events that can be measured via the QTc interval. We investigated the impact of obstructive sleep apnea on the change in repolarization after CABG and the association of change in repolarization with the occurrence of major adverse cardiac and cerebrovascular events. A total of 1,007 patients from 4 hospitals underwent an overnight sleep study prior to a nonemergent CABG. Electrocardiograms of 954 patients (median age: 62 years; male: 86%; mean follow-up: 2.1 years) were acquired prospectively within 48 hours before CABG (T1) and within 24 hours after CABG (T2). QTc intervals were measured using the BRAVO algorithm by Analyzing Medical Parameters for Solutions LLC. The change in T2 from T1 for QTc (ΔQTc) was derived, and Cox regression was performed. Compared with those without, patients who developed major adverse cardiac and cerebrovascular events (n = 115) were older and had (1) a higher prevalence of smoking, hypertension, diabetes mellitus, and chronic kidney disease; (2) a higher apnea-hypopnea index and oxygen desaturation index; and (3) a smaller ΔQTc. Cox regression analysis demonstrated a smaller ΔQTc to be an independent risk factor for major adverse cardiac and cerebrovascular events (hazard ratio: 0.997; P = .032). In the multivariable regression model, a higher oxygen desaturation index was independently associated with a smaller ΔQTc (correlation coefficient: -0.58; P < .001). A higher preoperative oxygen desaturation index was an independent predictor of a smaller ΔQTc. ΔQTc within 24 hours after CABG could be a novel predictor of occurrence of major adverse cardiac and cerebrovascular events at medium-term follow-up. Registry: ClinicalTrials.gov; Name: Undiagnosed Sleep Apnea and Bypass OperaTion (SABOT); URL: https://classic.clinicaltrials.gov/ct2/show/NCT02701504; Identifier: NCT02701504. Teo YH, Yong CL, Ou YH, etal. Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting. J Clin Sleep Med. 2024;20(1):49-55.

Effects of Hypoglycemia on Cardiovascular Function in Patients with Diabetes.

Hypoglycemia is common in patients with type 1 and type 2 diabetes (T1D, T2D), treated with insulin or sulfonylureas, and has multiple short- and long-term clinical implications. Whether acute or recurrent, hypoglycemia significantly affects the cardiovascular system with the potential to cause cardiovascular dysfunction. Several pathophysiological mechanisms have been proposed linking hypoglycemia to increased cardiovascular risk, including hemodynamic changes, myocardial ischemia, abnormal cardiac repolarization, cardiac arrhythmias, prothrombotic and proinflammatory effects, and induction of oxidative stress. Hypoglycemia-induced changes can promote the development of endothelial dysfunction, which is an early marker of atherosclerosis. Although data from clinical trials and real-world studies suggest an association between hypoglycemia and cardiovascular events in patients with diabetes, it remains uncertain whether this association is causal. New therapeutic agents for patients with T2D do not cause hypoglycemia and have cardioprotective benefits, whereas increasing the use of new technologies, such as continuous glucose monitoring devices and insulin pumps, has the potential to reduce hypoglycemia and its adverse cardiovascular outcomes in patients with T1D.

Cardiac Repolarization in HealthandDisease.

Abnormal cardiac repolarization is at the basis of life-threatening arrhythmias in various congenital and acquired cardiac diseases. Dysfunction of ion channels involved in repolarization at the cellular level are often the underlying cause of the repolarization abnormality. The expression pattern of the gene encoding the affected ion channel dictates its impact on the shape of the T-wave and duration of the QT interval, thereby setting the stage for both the occurrence of the trigger and the substrate for maintenance of the arrhythmia. Here we discuss how research into the genetic and electrophysiological basis of repolarization has provided us with insights into cardiac repolarization in health and disease and how this in turn may provide the basis for future improved patient-specific management.

ASC4START: A Phase IIIb, Open-Label, Randomized Study of Tolerability and Efficacy of Asciminib Versus Nilotinib in Patients with Newly Diagnosed Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia in Chronic Phase

Objectives: Tyrosine kinase inhibitors (TKIs) have greatly improved treatment outcomes for patients with newly diagnosed chronic myelogenous leukemia in chronic phase (CML-CP), transforming it into a chronic disease requiring long-term treatment. This emphasizes the need for treatments that combine high efficacy with a favorable safety profile, improving over currently available options. Asciminib is a first-in-class BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket (STAMP) which has been approved by the FDA with subsequent approvals worldwide for patients with Philadelphia chromosome-positive (Ph+) CML-CP, previously treated with ≥2 prior TKIs based on the results of the ASCEMBL (NCT03106779) trial. The ABL specificity of asciminib compared with the selectivity of second-generation (2G) TKIs can reduce off-target effects and improve tolerability while maintaining efficacy and reducing the probability of developing resistance. The ongoing ASC4FIRST (NCT04971226) study will evaluate the efficacy and safety of asciminib vs investigator-selected TKI in patients with newly diagnosed Ph+ CML-CP. Additional data on asciminib in newly diagnosed Ph+ CML-CP may help to address patient-centric objectives, in particular the ability of patients to remain on treatment without having to permanently discontinue due to adverse events (AEs). The ASC4START study (NCT05456191) will primarily evaluate the tolerability of asciminib vs the 2G TKI nilotinib in adult patients with newly diagnosed Ph+ CML-CP, as measured by the time to study treatment discontinuation due to adverse event (TTDAE). The study will also report on further safety, efficacy and quality of life (QoL) outcomes. Methods: This is a phase IIIb, multi-center, open-label, randomized study in patients ≥18 years of age with newly diagnosed Ph+ CML-CP. The trial will enroll approximately 541 patients with CML-CP diagnosed within 3 months of study entry and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients cannot be included if they have received previous treatment for CML with any other anticancer agents (except hydroxyurea and/or anagrelide), have confirmed central nervous system infiltration, or present impaired cardiac function or abnormalities in cardiac repolarization. Patients will be randomized 1:1 to receive asciminib 80 mg once daily or nilotinib 300 mg twice daily, both administered orally under fasting conditions; randomization will be stratified based on European Treatment Outcome Study long-term survival (ELTS) score at diagnosis (high vs intermediate vs low) to help achieve balance between the treatment arms (Figure). The primary endpoint is TTDAE, defined as the time from the date of the first dose of study treatment to the date of discontinuation of study treatment due to an AE. Secondary endpoints include type, frequency and severity of AEs; dose modifications due to AE; changes in laboratory values that fall outside pre-determined ranges; clinically notable ECG changes; time to discontinuation due to selected reasons (lack of efficacy/treatment failure/disease progression/suboptimal response/death); major molecular response (MMR), MR4, MR4.5, complete hematological response (CHR), and BCR::ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, progression-free survival and overall survival. Secondary endpoints related to QoL include change from baseline in overall scores and individual scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires QLQ-C30 and QLQ-CML24. Participants will be treated in the study until approximately 64 discontinuations due to AEs are met; treatment duration for an individual patient is expected to be 2‒4.5 years. Current status: The study is recruiting as of October 2022. This study was sponsored by Novartis Pharmaceuticals. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Toward ECG-based analysis of hypertrophic cardiomyopathy: a novel ECG segmentation method for handling abnormalities.

Abnormalities in impulse propagation and cardiac repolarization are frequent in hypertrophic cardiomyopathy (HCM), leading to abnormalities in 12-lead electrocardiograms (ECGs). Computational ECG analysis can identify electrophysiological and structural remodeling and predict arrhythmias. This requires accurate ECG segmentation. It is unknown whether current segmentation methods developed using datasets containing annotations for mostly normal heartbeats perform well in HCM. Here, we present a segmentation method to effectively identify ECG waves across 12-lead HCM ECGs. We develop (1) a web-based tool that permits manual annotations of P, P', QRS, R', S', T, T', U, J, epsilon waves, QRS complex slurring, and atrial fibrillation by 3 experts and (2) an easy-to-implement segmentation method that effectively identifies ECG waves in normal and abnormal heartbeats. Our method was tested on 131 12-lead HCM ECGs and 2 public ECG sets to evaluate its performance in non-HCM ECGs. Over the HCM dataset, our method obtained a sensitivity of 99.2% and 98.1% and a positive predictive value of 92% and 95.3% when detecting QRS complex and T-offset, respectively, significantly outperforming a state-of-the-art segmentation method previously employed for HCM analysis. Over public ECG sets, it significantly outperformed 3 state-of-the-art methods when detecting P-onset and peak, T-offset, and QRS-onset and peak regarding the positive predictive value and segmentation error. It performed at a level similar to other methods in other tasks. Our method accurately identified ECG waves in the HCM dataset, outperforming a state-of-the-art method, and demonstrated similar good performance as other methods in normal/non-HCM ECG sets.

Diabetes without Overt Cardiac Disease Is Associated with Markers of Abnormal Repolarization: A Case-Control Study.

Patients with diabetes mellitus (DM) are prone to advanced atherosclerosis, microvascular disease, and tissue fibrosis. Despite the increased risk for arrhythmias, little is known about cardiac repolarization abnormalities in DM. We aimed to determine whether abnormal T-wave morphology markers are common among patients with DM and no known cardiac disease. Patients were recruited and classified as having DM or impaired fasting glucose (IFG) according to accepted guidelines. Total cosine R to T (TCRT) and T-wave morphology dispersion (TMD) were computed with custom-designed software for randomly selected and averaged beats. Among 124 patients recruited; 47 were diagnosed with DM and 3 IFG. DM patients and the control group had similar clinical characteristics, other than statins and anti-diabetic drugs, which were more common among DM patients. Patients with DM/IFG had decreased TCRT values computed from a random beat (0.06 ± 0.10 vs. 0.43 ± 0.07, p < 0.01) and an average beat (0.08 ± 0.09 vs. 0.44 ± 0.06, p < 0.01), when compared with the control group. TMD parameters did not differ. In conclusion, TCRT is reduced in patients with DM and no known cardiac diseases. Further research is required to investigate whether repolarization-associated changes in DM are the consequence of subclinical atherosclerosis, diabetic cardiomyopathy, or a combination of the two.

Cardiac repolarization abnormalities in children with familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is an autoinflammatory disease that can have conduction disturbances and cardiac rhythm disorders as manifestations of cardiac involvement. The aim of the study is to assess the susceptibility of children with FMF to cardiac repolarization abnormalities and therefore arrhythmia in children with FMF.MethodsA cross sectional study conducted on 60 children had FMF and 40 age and sex matched healthy controls. Cardiac repolarization markers, cardiac dimensions and functions were assessed by electrocardiogram (ECG) and conventional echocardiography in patients and controls.ResultsThe mean ± SD age of the patients was 10.43 ± 3.472 years, corrected QT (QTc) and the ratio of peak to end T wave (Tpe) over QTc interval (Tpe /QTc) increased significantly in FMF patients more than healthy control (p value 0.023 and 0.022 respectively). P wave dispersion (Pd) was significantly higher in FMF patients with amyloidosis (p value 0.030). No significant difference was found in cardiac dimensions and functions between the two groups. We found a statistically negative correlation between Pd and age of patients at time of study, age of disease onset and age at diagnosis. On the other hand, we found a statistically significant positive correlation between Pd with number of attacks per year and disease severity score. Furthermore, Tpe/QTc ratio correlated with FMF 50 score, QTc correlated with 24 hours proteinuria. QT, JT intervals correlated with fibrinogen.ConclusionsFMF Patients may have increased risk of arrhythmia and should be monitored on regular basis. Compliance to colchicine therapy and better disease control might play a role in decreasing this risk.

PO-671-08 SPATIAL VENTRICULAR GRADIENT CAN DIFFERENTIATE HYPERTROPHIC CARDIOMYOPATHY FROM OTHER FORMS OF LEFT VENTRICULAR HYPERTROPHY

Diagnosis of hypertrophic cardiomyopathy (HCM) has far-reaching clinical implications. The gold standard non-invasive test for diagnosing HCM is cardiac MRI (CMR), but this is expensive and not readily available. Standard ECG measures of left ventricular hypertrophy may not differentiate HCM from other more benign causes of cardiac hypertrophy. The spatial ventricular gradient (SVG), a vectorcardiographic measure of global electrical heterogeneity (GEH), reflects global abnormalities in cardiac depolarization and repolarization, and may be able to distinguish HCM from other disorders.

Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study.

Background: The relationship between thyroid function and cardiac disease is complex. Both hypothyroidism and thyrotoxicosis can predispose to ventricular arrhythmia and other major adverse cardiovascular events (MACE), so that a U-shaped relationship between thyroid signaling and the incidence of MACE has been postulated. Moreover, recently published data suggest an association between thyroid hormone concentration and the risk of sudden cardiac death (SCD) even in euthyroid populations with high-normal FT4 levels. In this study, we investigated markers of repolarization in ECGs, as predictors of cardiovascular events, in patients with a spectrum of subclinical and overt thyroid dysfunction.Methods: Resting ECGs of 100 subjects, 90 patients (LV-EF > 45%) with thyroid disease (60 overt hyperthyroid, 11 overt hypothyroid and 19 L-T4-treated and biochemically euthyroid patients after thyroidectomy or with autoimmune thyroiditis) and 10 healthy volunteers were analyzed for Tp-e interval. The Tp-e interval was measured manually and was correlated to serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and thyroxine (FT4).Results: The Tp-e interval significantly correlated to log-transformed concentrations of TSH (Spearman's rho = 0.30, p < 0.01), FT4 (rho = −0.26, p < 0.05), and FT3 (rho = −0.23, p < 0.05) as well as log-transformed thyroid's secretory capacity (SPINA-GT, rho = −0.33, p < 0.01). Spearman's rho of correlations of JT interval to log-transformed TSH, FT4, FT3, and SPINA-GT were 0.51 (p < 1e−7), −0.45 (p < 1e−5), −0.55 (p < 1e−8), and −0.43 (p < 1e−4), respectively. In minimal multivariable regression models, markers of thyroid homeostasis correlated to heart rate, QT, Tp-e, and JT intervals. Group-wise evaluation in hypothyroid, euthyroid and hyperthyroid subjects revealed similar correlations in all three groups.Conclusion: We observed significant inverse correlations of Tp-e and JT intervals with FT4 and FT3 over the whole spectrum of thyroid function. Our data suggest a possible mechanism of SCD in hypothyroid state by prolongation of repolarization. We do not observe a U-shaped relationship, so that the mechanism of SCD in patients with high FT4 or hyperthyroidism seems not to be driven by abnormalities in repolarization.

Abstract 14476: Effects of Encaleret on Corrected QT Interval in Autosomal Dominant Hypocalcemia Type 1: Early Results From an Ongoing Phase 2b, Open-Label, Dose-Ranging Study

Introduction: Autosomal dominant hypocalcemia type 1 (ADH1) is caused by gain-of-function variants of the calcium-sensing receptor (CaSR) gene, resulting in receptor proteins with increased sensitivity to extracellular calcium. Individuals with ADH1 exhibit hypocalcemia, hypomagnesemia, hyperphosphatemia, and inappropriately low levels of PTH. Hypocalcemia and hypomagnesemia can slow cardiac repolarization and potentially prolong the QT interval in patients with ADH1. Prolongation of the QT interval can lead to potentially malignant ventricular arrhythmias. Calcilytics are antagonists of the CaSR with the potential to restore normal CaSR sensitivity in ADH1 and thereby normalize blood levels of calcium and magnesium. This study investigated the biochemical and ECG effects of encaleret, an investigational oral calcilytic, in individuals with ADH1. Methods: CLTX-305-201 [NCT04581629] is a 3-period, open-label, dose-ranging study of encaleret in adults with ADH1. In Period 1, supplements were discontinued 1 or 2 days prior to administering sequential, increasing daily doses of encaleret over 5 days with frequent biochemical monitoring. Standard 12-lead surface ECGs were recorded at baseline (BL) and on Day 5 (D5). Results: Data (mean±SD) from the first 6 participants are presented. BL and D5 values were compared as follows: • PTH: BL 3.4±4.5; D5 64.8±49.6 (nl 10-65 pg/mL; p&lt;0.01) • Albumin-corrected total calcium: BL 7.6±0.6; D5 9.0±0.5 (nl 8.4-10.2 mg/dL; p&lt;0.01) • Magnesium: BL 1.6±0.4; D5 2.0±0.5 (nl 1.6-2.6 mg/dL; p&lt;0.01) • Phosphate: BL 4.5±0.7; D5 2.9±0.5 (nl 2.3-4.7 mg/dL; p&lt;0.01) • QT c B: BL 452±9; D5 433±11 (nl &lt;440 msec; p&lt;0.01) There were no important changes or trends in heart rate, blood pressure, or other ECG intervals. Encaleret was well-tolerated and without serious adverse events. Conclusion: Hypocalcemic ADH1 study participants experienced abnormal cardiac repolarization manifested as prolongation of the QT interval at baseline. The consistent responses following encaleret treatment ADH1 participants provide preliminary evidence that encaleret, by raising blood levels of calcium and magnesium, may normalize cardiac repolarization in patients with ADH1. Longer-term evaluation of encaleret in ADH1 is ongoing.

Abstract 11535: Persistent Qt Prolongation After Doxorubicin Administration at Doses Similar to Adjuvant Breast Cancer Therapy in African Green Monkeys

Introduction: Cancer patients undergoing doxorubicin (Dox)-based chemotherapy often experience cardiac repolarization abnormalities, including electrocardiography (ECG)-derived QT and corrected QT (QTc) interval prolongation, which increases the risk for life-threatening arrhythmias such as torsades de pointes. We have previously reported that African Green monkeys exhibit CMR-derived myocardial fibrosis long-term after receiving Dox at doses similar to those experienced by women treated for breast cancer. Here, we sought to determine if QT/QTc prolongation persists after treatment cessation and its association with myocardial fibrosis. Methods: Five female African Green AGMs (AGMs) aged 13±1 years received Dox (30 - 60 mg/m 2 / biweekly IV, total cumulative dose: 240 mg/m 2 ) and underwent 12-lead ECG and CMR imaging with pre- and post-contrast T1 maps from which extracellular volume (ECV) was calculated, before and 15 weeks after the final dose of Dox treatment. A blinded paired and correlation analysis was performed on ECG-derived heart rate (HR), QRS, QT, QTc interval durations and ECV. Results: After Dox, all monkeys exhibited increased QT (BL: 323.2 ± 27.4 ms vs. Post-Dox: 366.4 ± 18.7 ms, p=0.002) and QTc (BL: 440.2 ± 22.8 ms vs. Post-Dox: 500.8 ± 22.0 ms, p=0.009) intervals, without any significant changes in HR or QRS duration (p=0.92 and p=0.47 respectively). Longer QTc intervals were associated with increases in ECV ( r =0.58, p=0.05) (Figure). Conclusions: AGMs that received Dox - in a fashion similar to adjuvant anthracycline chemotherapy for breast cancer- exhibited longer QT and QTc intervals associated with myocardial fibrosis. Our study suggests this may not be solely due to transient ion channel disruption from Dox but rather from persistent changes in the electrophysiological properties of cardiomyocytes and the extracellular matrix. Future longitudinal studies are needed to determine the clinical significance of these findings.

Interictal QTc abnormalities in patients with epilepsy: Effects of disease duration and anti-seizure medications

Epilepsy is associated with abnormalities in cardiac repolarization as corrected QT interval (QTc) prolongation. The aim of the study is to correlate QTc abnormalities to epilepsy duration and number and class of anti-seizure medications (ASMs).

Usefulness of cardiac screening in patients with systemic lupus erythematosus and anti-Ro/SSA antibodies.

Recent data suggest that some adult patients with autoimmune rheumatic diseases may develop cardiac conduction and repolarization abnormalities mediated by anti-Ro/SSA antibodies. We aim to investigate the utility of a cardiac screening in patients with systemic lupus erythematous (SLE) and anti-Ro/SSA positivity. SLE patients who consecutively attended a Rheumatology clinic during 1 year where evaluated for the presence and levels of anti-Ro/SSA antibodies, and clinical and biological markers of organ damage and disease activity. All participants underwent a cardiovascular anamnesis and physical examination, ECG, echocardiography, and 24-hour Holter. Of the 145 recruited patients, 49 (32%) had anti-Ro/SSA positivity. None had any degree of atrioventricular block in the ECG or Holter monitoring. No significant differences were observed between anti-Ro/SSA-positive vs. negative patients in terms of PR, QRS or QTc intervals. No clinically significant arrhythmias were recorded during Holter monitoring and no differences in average heart rate, heart rate variability, or atrial or ventricular ectopy burden were observed. Finally, no differences were found in echocardiographic measurements. In this study of SLE patients, anti-Ro/SSA positivity was not associated with significant alterations in ECG, echocardiography, or 24-hour Holter. These findings do not support ordinary cardiac evaluation in these patients. (Clinicaltrials.gov registration number: NCT02162992).

Abnormal Cardiac Repolarization After Seizure Episodes in Structural Brain Diseases: Cardiac Manifestation of Electrical Remodeling in the Brain?

BackgroundAbnormal cardiac repolarization is observed in patients with epilepsy and can be associated with sudden death. We investigated whether structural brain abnormalities are correlated with abnormal cardiac repolarizations in patients with seizure or epilepsy.Methods and ResultsWe retrospectively analyzed and compared 12‐lead ECG parameters following seizures between patients with and without structural brain abnormalities. A total of 96 patients were included: 33 women (17 with and 16 without brain abnormality) and 63 men (44 with and 19 without brain abnormality). Brain abnormalities included past stroke, chronic hematoma, remote bleeding, tumor, trauma, and postsurgical state. ECG parameters were comparable for heart rate, PR interval, and QRS duration between groups. In contrast, corrected QT intervals evaluated by Fridericia, Framingham, and Bazett formulas were prolonged in patients with brain abnormality compared with those without (women: Fridericia [normal versus abnormal], 397.4±32.7 versus 470.9±48.9; P=0.002; Framingham, 351.0±40.1 versus 406.2±46.1; P=0.002; Bazett, 423.8±38.3 versus 507.7±56.6; P<0.0001; men: Fridericia, 403.8±30.4 versus 471.0±47.1; P<0.0001; Framingham, 342.7±36.4 versus 409.4±45.8; P<0.0001; Bazett, 439.3±38.6 versus 506.2±56.8; P<0.0001). QT dispersion and Tpeak−Tend intervals were comparable between groups. We also observed abnormal ST‐segment elevation in 5 patients. Importantly, no patients showed fatal arrhythmias during or after seizures.ConclusionsOur study demonstrated that brain abnormalities can be associated with abnormal cardiac repolarization after seizures, which might be a manifestation of electrophysiological remodeling in the brain.

Electrocardiographic Manifestations of COVID-19: Effect on QRS and QTc

Introduction: Prolonged QT intervals have been reported in patients with COVID-19. Virus particles have been demonstrated in heart tissue and direct effects on cardiac function have been noted. We hypothesize that cardiac electrophysiologic abnormalities may be a direct effect of COVID-19.Methods: 814 patients with RT-PCR proven COVID-19 were admitted and 614 discharged home from St. Francis Hospital Emergency Room (ER) between March-May 2020. Corrected QT (QTc) and QRS intervals were measured from ECG’s performed in the ER prior to intervention or administration of QT prolonging drugs. QTc and QRS intervals were evaluated as a function of disease severity (patients admitted versus discharged home; inpatients admitted to medical vs critical care unit) and cardiac involvement (troponin elevation >0·03 ng/ml, elevated B-natriuretic peptide (BNP) or NT pro-BNP >500 pg/ml). Multivariable analysis was used to test for significance (pResults: Average age was 66 ± 16 years, 45% female, 46% hypertensive, 28% diabetic, average body mass index of 28·7 ± 6·4 kg/m 2 . Baseline QTc of inpatients was prolonged compared to patients discharged home (450·1 ± 30·2 msec versus 423·4 ± 21·7msec, pConclusion: Abnormalities of cardiac activation (QRS) and repolarization (QTc) are direct manifestations of COVID-19 and early markers for progression to severe disease. The ECG, a readily accessible tool, identifies cardiac involvement and can be used to predict disease course and mortality.Funding Statement: Funding provided by the research foundation at Catholic Health of Long Island.Declaration of Interests: None.Ethics Approval Statement: The study was submitted for expedited Internal Review Board Review and received a waiver given its retrospective nature of data analysis in anonymized subjects.

Electrocardiographic Manifestations in Patients with COVID-19: Daegu in South Korea.

As the coronavirus disease 2019 (COVID-19) spreads worldwide, cardiac injury in patients infected with COVID-19 becomes a significant concern. Thus, this study investigates the impact of several electrocardiogram (ECG) parameters and disease severity in COVID-19 patients. Seven medical centers in Daegu admitted 822 patients with COVID-19 between February and April 2020. This study examined 267 patients among them who underwent an ECG test and evaluated their biochemical parameters like C-reactive protein (CRP), log N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), cardiac enzyme, and ECG parameters (heart rate, PR interval, QRS interval, T inversion, QT interval, and Tpe [the interval between peak to end in a T wave]). Those patients were divided into 3 groups of mild (100 patients), moderate (89 patients), and severe (78 patients) according to clinical severity score. The level of CRP, log NT-proBNP, and creatinine kinase-myocardial band were significantly increased in severe patients. Meanwhile, severe patients exhibited prolonged QT intervals (QTc) and Tpe (Tpe-c) compared to mild or moderate patients. Moreover, deceased patients (58; 21.7%) showed increased dispersion of QTc and Tpe-c compared with surviving patients (78.2±41.1 vs. 40.8±24.6 ms and 60.2±37.3 vs. 40.8±24.5 ms, both p<0.05, respectively). The QTc dispersion of more than 56.1 ms could predict the mortality in multivariate analysis (odd ratio, 11.55; 95% confidence interval, 3.746-42.306). COVID-19 infections could involve cardiac injuries, especially cardiac repolarization abnormalities. A prolonged QTc dispersion could be an independent predictable factor of mortality.

Abstract 17250: Quantitative T Wave Morphology Analysis in Rett Syndrome Patients

Introduction: Rett syndrome (RTT) is a genetic neurologic disorder associated with a high incidence of sudden death. Abnormal cardiac repolarization is a potential risk factor for sudden death in this population. RTT patients may have prolonged corrected QT (QTc) on electrocardiogram (ECG) that is a sensitive marker of torsades des pointes. However, other repolarization markers such as T wave morphology, the time it takes the T wave to return to baseline from peak amplitude (Tpeak - Tend), and heart rate corrected JTpeak have not been studied. Hypothesis: Rett syndrome patients have abnormal cardiac repolarization. Methods: Retrospective T wave analysis was performed using QT Guard software. T wave morphology and heterogeneity parameters of RTT patients were compared to ECGs of age and sex matched healthy controls. A composite T wave morphology score was calculated from individual feature of flatness, notching, and asymmetry; a higher score means more abnormal morphology. Heterogeneity of repolarization was represented by the principal component analysis ratio 2 (PCA-2). Results: 57 Rett patients (260 ECG) and 121 controls (134 ECG) were studied. The RTT group had longer QTc (p = 0.001) along with more abnormal T-wave morphology scores and heterogeneity parameters when compared to controls (Tables 1, 2). RTT patients without long QTc also had more abnormal morphology scores than controls (p = 0.001). Conclusion: Cardiac repolarization is diffusely abnormal in RTT even in the absence of long QTc. T wave morphology analysis may be used to detect and monitor abnormal cardiac repolarization in RTT in clinical practice.