Electrocardiogram Parameters Research Articles

The Value of Combined Detection of Serum BNP, Cardiac Troponin-I and Dynamic Electrocardiogram in Early Clinical Diagnosis and Prognosis of Patients with Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease resulting from myocardial ischemia and necrosis due to coronary artery occlusion. AMI is characterized by a sudden onset and high mortality, underscoring the significance of early diagnosis and treatment for improving patient prognosis. This study endeavors to assess the utility of a combined assessment involving serum brain natriuretic peptide (BNP), cardiac troponin-I (cTnI), and dynamic electrocardiogram (ECG) in the early clinical diagnosis and prognosis prediction of AMI. This paper constitutes a retrospective study. All enrolled patients underwent dynamic ECG examination. The study compared the serum levels of BNP and cTnI, along with pertinent dynamic ECG parameters [turbulence slope (TS) and standard deviation (SDNN) of the 24-hour interval between normal atrial depolarization and ventricular depolarization (R-R)], between the observation group (AMI patients) and the control group (patients with unstable angina (UA)). To evaluate the early diagnostic potential of AMI, we utilized receiver operating characteristic (ROC) curves to analyze serum BNP, cTnI, dynamic ECG, and their combined utility. Furthermore, a follow-up period of 6 months was conducted for AMI patients to record major adverse cardiovascular events (MACE). In the observation group, the serum levels of BNP and cTnI were significantly higher than those in the control group (p < 0.001), while dynamic ECG parameters, specifically TS and SDNN, were significantly lower in the observation group compared to the control group (p < 0.001). The results obtained from the ROC curve analysis revealed that the area under the curve (AUC) for BNP, cTnI, dynamic ECG, and their combination in early AMI diagnosis were 0.838, 0.887, 0.874, and 0.974, respectively. The 95% confidence intervals (CI) were 0.781~0.884, 0.836~0.926, 0.822~0.915, and 0.942~0.991, respectively. Sensitivity values were 64.29%, 82.14%, 91.07%, and 88.39%, and specificity values were 91.00%, 88.00%, 70.00%, and 98.00%, respectively. Significantly, the combination of all three markers demonstrated superior efficacy in early AMI diagnosis compared to any single index (p < 0.05). During the 6-month follow-up of 112 AMI patients, 22 experienced MACE. The MACE group exhibited notably higher serum BNP and cTnI levels compared to the non-MACE group. Additionally, dynamic electrocardiogram parameters TS and SDNN demonstrated a significant decrease (p < 0.05) in the MACE group. The combined assessment of serum BNP, cTnI, and dynamic electrocardiogram enhances the early clinical diagnostic potential for AMI and holds value in assessing the prognosis of AMI patients.

Comparison of Novel Telemonitoring System Using the Single-lead Electrocardiogram Patch With Conventional Telemetry System.

Although a single-lead electrocardiogram (ECG) patch may provide advantages for detecting arrhythmias in outpatient settings owing to user convenience, its comparative effectiveness for real-time telemonitoring in inpatient settings remains unclear. We aimed to compare a novel telemonitoring system using a single-lead ECG patch with a conventional telemonitoring system in an inpatient setting. This was a single-center, prospective cohort study. Patients admitted to the cardiology unit for arrhythmia treatment who required a wireless ECG telemonitoring system were enrolled. A single-lead ECG patch and conventional telemetry were applied simultaneously in hospitalized patients for over 24 hours for real-time telemonitoring. The basic ECG parameters, arrhythmia episodes, and signal loss or noise were compared between the 2 systems. Eighty participants (mean age 62±10 years, 76.3% male) were enrolled. The three most common indications for ECG telemonitoring were atrial fibrillation (66.3%), sick sinus syndrome (12.5%), and atrioventricular block (10.0%). The intra-class correlation coefficients for detecting the number of total beats, atrial and ventricular premature complexes, maximal, average, and minimal heart rates, and pauses were all over 0.9 with p values for reliability <0.001. Compared to a conventional system, a novel system demonstrated significantly lower signal noise (median 0.3% [0.1-1.6%] vs. 2.4% [1.4-3.7%], p<0.001) and fewer episodes of signal loss (median 22 [2-53] vs. 64 [22-112] episodes, p=0.002). The novel telemonitoring system using a single-lead ECG patch offers performance comparable to that of a conventional system while significantly reducing signal loss and noise. Clinical Research Information Service Identifier: KCT0008176.

Measuring of cardiac electrical system function among salbutamol inhaled children – A cohort study

Background: Salbutamol is widely recognized as an effective rescue therapy for acute asthma attacks. However, the usage of inhaled β2-agonists, including salbutamol, has been related to an amplified hazard of cardiovascular disease, as suggested by several studies. Despite this association, there is an absence of sufficient facts regarding the cardiac electrophysiological possessions of inhaled β2-agonists in children. Aim and Objectives: The present study was to explore the cardiac electrophysiological effects of inhaled salbutamol in children. By examining the specific impact of salbutamol on cardiac electrophysiology, this study aimed to contribute valuable insights into the potential cardiovascular effects of inhaled β2-agonists in the pediatric population. Materials and Methods: This cohort study involved 130 individuals of both sexes, levels in age from 1 to 12 years. Salbutamol nebulization was administered to the children at a dosage of 0.15 mg/kg/dose, mixed with normal saline at a ratio of 1:3, using a nebulizer. Cardiac parameters including heart rate, T axis, P axis, QTc interval, QRS axis, QRS interval, and PR interval were recorded before and after nebulization using a computerized electrocardiogram (ECG). Results: The outcomes of the work presented that following nebulization, there was a major rise in heart rate and a notable decline in the PR interval, T axis, and P axis. However, no analytical significant deviations were observed in the QRS axis, QTc interval, and QRS interval. Conclusion: The study demonstrates that within a time frame of 5–15 min after inhaling a single standard dose of salbutamol, significant changes in the ECG parameters occur. These changes in cardiac electrophysiology may contribute to an amplified occurrence of arrhythmias in some patients getting salbutamol treatment. It is important to note that the frequent use of high doses of salbutamol for asthmatic exacerbations may potentially lead to more severe cardiac adverse effects.

Epilepsy's effect on cardiac rhythm and the autonomic nervous system.

Sudden unexpected death in epilepsy is the most common cause of death in young patients with epilepsy. The aim of this study was to evaluate changes in interictal electrocardiogram parameters and sympathetic skin responses as markers of autonomic dysfunction in patients with epilepsy and to determine their effects on the type and duration of epilepsy, frequency of seizures, and responses to treatment. A total of 97 patients with epilepsy and 94 healthy controls were recruited. We recorded their clinical and demographic characteristics and analyzed sympathetic skin response latency and amplitude, electrocardiogram recordings, and seven cardiac rhythm parameters: P-wave duration, PR segment, QRS duration, QT interval, QT interval distribution, Tpe duration, and Tpe/QT interval ratio. P-wave durations, T-wave durations, QT and QT interval durations, and Tpe and sympathetic skin response latency were significantly longer among patients with epilepsy than the controls, and their heart rate was significantly lower. However, sympathetic skin response latency and heart rate were negatively correlated, and T-wave duration, QT duration, QT interval duration, and Tpe were positively correlated. Our results from interictal electrocardiograms indicate clinically significant arrhythmias among patients with epilepsy and the correlation of such arrhythmias with sympathetic skin responses. Thus, noninvasive tests that evaluate the autonomic system should be used to predict the risk of sudden unexpected death in epilepsy among patients with epilepsy.

Qualitative and Quantitative Electrocardiogram Parameters in a Large Cohort of Children with Duchenne Muscle Dystrophy in Comparison with Age-Matched Healthy Subjects: A Study from South India.

Electrocardiography (ECG) remains an excellent screening tool for cardiac assessment in Duchenne muscular dystrophy (DMD), but an accurate interpretation requires comparison with age-matched healthy controls. We examined various ECG parameters in children with DMD, in comparison with age-matched controls. Standard 12-lead ECG tracings of serial patients were screened for quality and selected. Controls were healthy, age-matched school-going children. Both quantitative and qualitative ECG parameters were analyzed. After screening, ECGs from 252 patients with DMD (8.32 ± 3.12 years, 2-21 years) and ECGs from 151 age-matched healthy controls (9.72 ± 2.23, 4-19 years) were included. A significantly higher heart rate, shorter R-R interval, and taller R wave in V1 were seen across all age group of DMD in comparison to controls, with the difference increasing with age. While QT prolongation was seen in all age groups of DMD, QTc prolongation was seen only at 10 years or more. Incomplete right bundle branch block (RBBB) and pathological Q waves in inferolateral leads were exclusive in DMD, with the latter declining with age. Evidence for left ventricular (LV) pathology, such as tall R in V5/V6, increase in SV1 + RV6 height, and QRS complex duration, were seen only in the age group of 10 years or more. Stratification based on age and comparison with age-matched healthy subjects showed that several ECG parameters were influenced by age, and it also identified age-dependent evidence for LV pathology and QTc prolongation in DMD.

The Impact of Coronary Sinus Reducer on Arrhythmic Properties in Patients with Refractory Angina.

Treatment with a coronary sinus reducer (CSR) is a new therapeutic option for refractory angina patients. Preclinical studies have shown antiarrhythmic properties of coronary sinus narrowing. The possible antiarrhythmic effect of CSR implantation is unknown. This study aimed to determine the possible antiarrhythmic effects of CSR implantation as assessed by high-resolution electrocardiogram (hrECG) parameters. 24 patients from the Crossroad study randomized to either CSR treatment (n = 12) or a sham procedure (n = 12) had hrECG recorded at baseline and after 6 months. T-peak and T-end interval (TpTe) defined as the time difference between the peak amplitude of the T wave and the global end of the T wave, spatial angle between QRS complex and T axis defined as the angle between the ventricular depolarization and repolarization vectors using maximal (QRSTP) and mean (QRSTM) vector amplitudes and spatial ventricular gradient (SVG) calculated as integral of ECG voltages over the entire QRST complex were analyzed. Additionally, we analyzed parameters of QT and heart rate variability using time and frequency domain. At baseline, all analyzed parameters were comparable between both groups and heart rate remained constant. The intragroup analysis did not show any significant change in TpTe, QRSTP, QRSTM, SVG, QT, and heart rate variability at follow-up. Furthermore, intergroup comparison between CSR implantation and sham procedure also did not show any significant difference in the change of analyzed parameters. Compared to the sham procedure, CSR implantation did not demonstrate a significant impact on the arrhythmogenic substrate assessed with hrECG. Unique Identifier: NCT04121845, https://classic.clinicaltrials.gov/ct2/show/NCT04121845.

Evaluating numerous techniques for the effects of electromagnetic waves on the Electro Cardio Gram (ECG)

&lt;p&gt;Nowadays, due to the widespread use of mobile phones and the proliferation of mobile towers the human body parts especially the heart are getting affected. Furthermore, these waves are ubiquitous in our modern society, with various sources emitting these waves in our environment. As medical devices become more prevalent and wireless technologies continue to advance, concerns have been raised regarding the potential impact of electromagnetic waves on human health. It is important to monitor the condition of your heart. With the increase in the number of mobile phones, there is also an increase in electromagnetic radiation, which can affect the human heart. The heart is an important component of the human body and an electrocardiogram (ECG) can provide valuable information about its condition. ECG parameters can show how well the heart is working. In this paper, the author proposes how ECG parameters change under the influence of mobile phones in three different situations. A comprehensive experimental setup was devised. A group of healthy human subjects volunteered to participate in the study, with each subject undergoing ECG recording under controlled conditions. The subjects were exposed to varying intensities and frequencies of electromagnetic waves generated by a standardized source. Statistical analysis was performed to compare the ECG measurements obtained during exposure to electromagnetic waves with those obtained in a controlled environment without electromagnetic wave exposure. This study contributes to the growing body of research on the potential health effects of electromagnetic waves. By specifically focusing on the ECG signal, which is vital for cardiovascular diagnostics, this research provides valuable insights into the safety and reliability of using ECG in environments with electromagnetic wave exposure. The findings will help inform healthcare professionals, engineers, and policymakers to establish appropriate guidelines and safety measures concerning the use of medical devices and wireless technologies in proximity to patients or individuals with cardiac conditions.&lt;/p&gt;

Is left bundle branch pacing (LBBP) associated with better depolarization and repolarization kinetics than right ventricular mid septal pacing (RVSP)? - Comparison of frontal QRS -T angle in patients with LBBP, RVSP and normal ventricular conduction

AimsTo assess the frontal QRS- T angle (f QRS- T angle) in patients with left bundle branch pacing (LBBP) as compared to right ventricular mid septal pacing (RVSP) implanted for symptomatic high degree atrioventricular (AV) block and to compare with control subjects with normal ventricular conduction (CSNVC) MethodsA total of one-fifty subjects were chosen (50 patients with LBBP, 50 patients with RVSP and 50 CSNVC). The indication for pacemaker implantation was symptomatic high degree AV block. Baseline clinical and electrocardiogram (ECG) parameters like QRS duration (QRSD), QRS axis and f QRS-T angle and Ejection Fraction (EF) were assessed. f QRS-T angle was measured as the difference between the computerised mean frontal QRS and T wave axes in the limb leads. If the difference between the QRS axis and T-wave axis exceeds 180°, then the resultant QRS-T angle would be calculated as 360° minus the absolute angle to obtain a value between 0° and 180°. Baseline, immediate post procedural and 6 month follow up (f/u) ECGs and EF were chosen for the analysis. ResultsPatients who underwent LBBP had significantly shorter paced QRSD than patients who had undergone RVSP (112 ± 12 ms vs 146 ± 13 ms; 95 % confidence interval (CI): 43, −31; p<0.001). There was no significant difference in the QRSD before and after LBBP. The QRSD before and after pacing in RVSP was 111 ± 27 ms and 146 ± 13 ms; 95 % CI: 43, −28; p < 0.001. The QRSD in control patients with NVC was 82.94 ± 9.59 ms.RVSP was associated with wider f QRS-T angle when compared with LBBP (103 ± 53° vs 82 ± 43°; 95 % CI: 39, −1.0; p = 0.037). The baseline and immediate post procedure f QRS-T angle in LBBP was 70 ± 48° and 82 ± 43°; 95 % CI: 31, 5.3; p = 0.2. At 6 months f/u, the f QRS-T angle was 61 ± 43°; 95 % CI: 8.5, 35; p=0.002. The baseline and immediate post procedure f QRS-T angle in RVSP was 67 ± 51° and 103 ± 53°; 95 % CI: 54, −17; p < 0.001. At 6 months f/u, the f QRS-T angle in RVSP group was 87 ± 58°; 95 % CI: 2.6, 29; p = 0.020. The f QRS T angle in control patients with NVC was 24 ± 16°. When subgroup analysis was done the difference in the f QRS-T angle was significant between RVSP and LBBP groups only in patients who had wide QRS escape.The mean LVEF at 6-month follow-up in LBBP vs RVSP was 61 ± 3.7 % vs 57.1 ± 7.8 %; 95 % CI:1.48, 6.32, p = 0.002. In the RVSP group, three patients developed pacing induced cardiomyopathy (PIC) whereas no patients in the LBBP group developed PIC at 6-month follow-up; p=0.021. One patient with PIC had deterioration of functional status with new onset HF symptoms. The patient symptoms improved with medical therapy and needed no hospitalisation. The patient declined further interventions including upgradation to CRT or LBB pacing. No deaths or ventricular arrhythmias were observed during the study period. ConclusionLBBP is associated with narrower f QRS-T angle as compared to RVSP both at post implant period and at 6 month f/u period. These findings might be due to the more physiological depolarization and repolarization kinetics associated with LBBP. RVSP was associated with 6 % incidence of PIC. Hence wide f QRS-T angle might be a predictor of PIC.

Significant delayed conduction and characteristic ventricular tachycardias in patients with cardiac sarcoidosis and electrical storm.

Electrical storm (ES) of ventricular tachyarrhythmias (VTAs) is an important cause of sudden death in patients with cardiac sarcoidosis (CS). VTAs in CS are associated with myocardial scarring and inflammation. However, little is known about the risk factors of ES in patients with CS and VTAs. The objective of this study is to clarify the characteristics and risk factors for the development of ES in patients with CS. The study population included consecutive 52 patients with CS and sustained VTA. Twenty-five out of 52 patients experienced ES. We evaluated clinical characteristics, imaging modalities, and electrocardiogram (ECG) parameters to determine the risk factors associated with ES. Half of the patients experienced VTAs as the initial symptom of sarcoidosis, and eight patients had ES as the initial VTA episode. There were no differences in cardiac imaging abnormalities between patients with and without ES. Among ECG markers, significant QRS fragmentation (odds ratio [OR]: 7.9, p = .01) and epsilon waves (OR: 12.24, p = .02) were associated with ES. Among the ventricular tachycardia (VT) characteristics, multiple morphologies of monomorphic VTs (OR: 10.9, p < .01), short VT cycle lengths (OR: 12.5, p < .01), and polymorphic VT (OR: 13.5, p < .01) were associated with ES. Bidirectional VTs were detected in 10 patients with ES and one patient without ES. Immunosuppressive therapy relieved ES in some patients. ES was common in patients with CS and VTAs. Significant depolarization abnormalities that appeared as QRS fragmentation, epsilon waves, and specific VT characteristics were associated with ES.

Electrocardiographic characteristics of pediatric and adolescent football players

Electrocardiographic characteristics of children and adolescents present differences compared to adults. The aim of our work was to study electrocardiograms (ECGs) of football male players from childhood to late adolescence and examine if the ECG parameters are influenced by systematic exercise. One thousand fifty-four football players participated and formed four groups. Group A included 89 players aged 5–7 years, group B 353 players aged 8–11 years, group C consisted of 355 football players 12-15 yearsold and group D of 257 players with 16–18 years of age. All participants underwent preparticipation screening, including 12-lead surface ECG. Heart rate (HR), PR, RR, QRS, QT, QTc intervals, QT dispersion (QTdisp) and QRS axis were calculated. All ECGs were evaluated according to the current preparticipation cardiac screening guidelines, that refer to athletes aged 12–35 years and do not include pediatric players. Eleven percent of the participants presented an ECG finding. Group D obtained the lowest values of HR, QTc and the highest of PR, RR, QRS, QT intervals and QTdisp, whereas no differences in QRS axis were reported. Incomplete Right Bandle Branch Block (RBBB) was the most frequent ECG peculiarity, detected in 7.3% of the participants. Years of training were statistically significantly correlated to HR, PR, RR, QRS and QT intervals. In conclusion, guidelines for ECG interpretation of athletes in childhood, early and late adolescence are needed.

Use of hydrobalneotherapy in ambulatory rehabilitation of patients with post-COVID syndrome

BACKGROUND: Post-COVID syndrome ostcoid syndrome is a consequence of the multimodal systemic effect of the SARS-CoV-2 virus on the human body, and leads to a variety of clinical symptoms that require correction. In particular, there is an increase in the level of allostatic load and the risk of maladaptation. One of the means of effective non-drug effects on the separated consequences of COVID-19 is the use of hydrobalneotherapy methods as part of a rehabilitation course.&#x0D; AIM: To study the influence of various hydrobalneotherapy methods as part of comprehensive outpatient rehabilitation on the clinical-functional and psychoemotional status of patients with post-COVID syndrome.&#x0D; MATERIALS AND METHODS: 160 patients undergoing outpatient rehabilitation for manifestations of post-COVID syndrome, 74 men and 86 women, with a median age of 50 [43; 55.1] years, were comprehensively examined. Patients were randomized to 4 groups of 40, depending on the non-drug exposure method in the rehabilitation program: 1st group ― with the inclusion in the individual rehabilitation program of a course of chloride-sodium mineral baths in the amount of 10 procedures, 2nd group ― patients who were assigned a 10-day course of hot tubs, 3rd group ― 40 patients, along with exercise therapy, who underwent a 10-day course of general baths "Biolong", and 4th, control group of patients who did not undergo outpatient rehabilitation.&#x0D; RESULTS: The most frequent complaints were increased fatigue ― 88.8% of subjects, memory loss ― 46.9%, headache and dizziness ― 38.8%, dyspnea during physical activity ― 35.6%. The most frequent electrocardiogram parameters were sinus tachycardia (4.4%) and sinus bradycardia (8.1%). The mean allostatic load index of all patients was 3 [2; 3], which corresponds to the average allostatic overload. Against the background of rehabilitation measures with the inclusion of preformed physical factors, regression of the main complaints (weakness was detected in 24.2% of cases, memory decline ― in 20%, headache, dizziness ― in 17.5%, dyspnea ― in 15%, sleep disturbance ― in 10%, tachycardia and discomfort in the heart area ― in 7.5%) and improvement of electrocardiogram parameters were noted: sinus tachycardia and ventricular extrasystole were not noted, bradycardia was recorded in 2.5% of cases instead of 8.1%, repolarization process disorders ― in 2.5% instead of 8.1% before rehabilitation. In the group of patients who received whirlpool baths, improvement of external respiratory function parameters was noted: forced vital capacity of lungs increased by 12.1% (p 0.01), forced expiratory volume in the 1st second ― by 9.6% (р 0.05), the distance traveled according to the results of the test with 6-minute walking increased by 2.2% (р 0.05). In the group of those who received general baths with the preparation "Biolong", there was registered an increase in forced expiratory volume in the 1st second by 9.4% (р 0.05), an increase in the distance traveled during the 6-minute walk test by 8, 3% (р 0.05), decrease in norepinephrine level by 17.4% (р 0.05), adrenaline level by 13% (р 0.05) and cortisol level by 26.2% (р 0.01), glutathione peroxidase activity level by 13.6% (р 0.05). In the group of patients who received sodium chloride baths, there was a tendency to improvement of central hemodynamic parameters, reduction of adrenaline and noradrenaline parameters by 14.5% and 19.7% respectively (р 0.05). All rehabilitation groups showed a decrease in the Beck depression scale and Spielberger anxiety scale, K. Maslach questionnaire (emotional exhaustion and reduction of personal achievements), Bass–Perry aggression level questionnaire and Schulte table (mental stability), as well as a decrease in the level of allostatic load. In the control group, no dynamics of complaints and indicators was noted.&#x0D; CONCLUSION: In patients with post-COVID syndrome, a variety of complaints and a number of electrocardiogram disorders, clinical and functional parameters were identified. The study revealed positive dynamics against the background of the rehabilitation course with the inclusion of hydrobalneotherapy methods in the form of significant regression of complaints, clinical and functional disorders and changes in psychoemotional background and cognitive status. A decrease in allostatic load was noted after a course of non-drug rehabilitation.

Integral indicators of cardiotoxicity of lead and cadmium on the background of physical activity

Introduction. Modern metallurgical production is characterized by mixed exposure of workers to harmful chemicals, of which lead and cadmium are the most common. A high physical workload is yet another occupational risk factor for metallurgists. &#x0D; Objective. Experimental study of effects of lead or cadmium and physical load on integral indicators of cardiotoxicity in rats.&#x0D; Materials and methods. We have carried out two 6-week experiments on rats to study integral indicators of cardiotoxicity of lead or cadmium and their changes under effect of physical activity. Solutions of lead or cadmium salts were administered intraperitoneally three times a week. Physical workload was simulated on a treadmill (10 min/day, 5 days a week). At the end of the experiment, electrocardiogram and blood pressure parameters were registered non-invasively.&#x0D; Results. Lead and cadmium had a cardiotoxic effect manifested by ECG changes. No pronounced hemodynamic changes were observed in our studies. According to ECG parameters, physical load slightly mitigates cardiotoxic effects of lead, but enhances manifestations of cadmium toxicity.&#x0D; Limitations. Data comparison can be affected by the fact that both outbred and inbred rats were used in the experiments. Caution should be taken when extrapolating animal data to humans since electrophysiological processes in the work of the heart differ in small rodents and large mammals.&#x0D; Conclusion. The established ambiguity of the impact of the physical workload on cardiotoxic effects of heavy metals necessitates further studies of this problem.

Abstract LB_A01: Rapidly cleared MCL1 inhibitor TTX-810 showing robust efficacy in preclinical tumor models with no effects on cardiomyocytes in vitro and in vivo

Abstract MCL1, an anti-apoptotic protein frequently amplified in cancer, confers resistance to standard of care, thus highlighting its importance as a therapeutic target. However, the involvement of MCL1 in cardiomyocyte function raises concerns for safely targeting the protein in cancer patients. MCL1 inhibitors currently in clinical trials exhibit shortcomings, either due to insufficient potency or extended half-lives that heighten the risk of cardiotoxicity. This study systematically explores MCL1 inhibitor-induced cell dynamics in cancer cells and healthy cardiomyocytes. TTX-810, a potent, selective, and rapidly-cleared MCL1 inhibitor, was used to identify a treatment regimen that induces efficacy, but spares healthy cardiomyocytes. TTX-810 demonstrates potent and reversible binding to the BH3-binding groove of human MCL1 (KD = 0.3 nM). It inhibits the interaction of MCL1 with the pro-apoptotic effector protein BAK or BH3-only protein BIM in cells in a dose- and time-dependent manner, leading to activation of the intrinsic apoptotic cascade and cancer cell death. At suprapharmacologic concentrations and extended exposure durations TTX-810 does induce apoptosis in human iPSC-derived cardiomyocytes, aligning with the recognized mechanism of MCL1 inhibitor-related cardiotoxicity. In contrast, short-term TTX-810 exposure induces efficient cancer cell killing in vitro, and has no impact on cell viability, apoptosis induction, or troponin I release in human iPSC-derived cardiomyocytes, even at high concentration. Similarly, TTX-810 induces strong monotherapy efficacy with once weekly in vivo dosing in an aggressive AML cancer model that is resistant to current standard of care agents like Venetoclax or Azacytidine. Repeated once weekly dosing in dogs over 4-weeks had no impact on troponin I levels in blood, electrocardiogram parameters (PR, QRS, QT and calculated QTcV intervals), heart rate, nor cardiac tissue morphology. In conclusion, this study identifies an optimal TTX-810 treatment regimen that effectively targets cancer cells, while preserving healthy cardiomyocytes. The study also demonstrates that a minimum exposure time is sufficient for efficacy, and this effect is even more pronounced when combined with standard-of-care agents. Moreover, limiting the exposure time expands the TTX-810 therapeutic window with regard to cardiotoxicity, which was validated in GLP toxicology studies in dogs and positions TTX-810 for future clinical development. Citation Format: Ulrike Rauh, Virendar Kaushik, Sabine Pilari, Georgios Kosmidis, Michael Serrano-Wu, Guo Wei, Weiqun Zhang, Stefan Kaulfuss, Kai Thede, Guillaume Poncet-Montange, Douglas Daniels, Christopher T Lemke, Brian Hubbard, Todd R. Golub. Rapidly cleared MCL1 inhibitor TTX-810 showing robust efficacy in preclinical tumor models with no effects on cardiomyocytes in vitro and in vivo [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A01.

Assessment of Cardiac Arrhythmia Risk in Children with Multisystem Inflammatory Syndrome

Objectives: This study intended to investigate laboratory markers and ventricular repolarization in electrocardiograms (ECGs) of children with multisystem inflammatory syndrome (MIS-C). Methods: Children with MIS-C from a single center were included. The study was conducted from January 27, 2022, to January 1, 2023. Basal ECGs, taken at the beginning (before treatment), were evaluated. The 12-lead ECG parameters, QT, QTc, T-peak to T-end (TpTe) distances, TpTe dispersion, and TpTe/QT ratio were compared with the healthy control group. Results: The QT interval, QTc duration, Tp-e distance, Tp-e dispersion, and Tp-e/QTc ratio were prominently higher in the patient group. Cardiac troponin I, NT-proBNP, D-dimer, biochemical data, CRP, and sedimentation also increased in these patients. In the severe MIS-C group, Tp-e dispersion duration was longer than in the mild MIS-C group (P = 0.04). QT duration was positively correlated with troponin I. The D-dimer level was positively correlated with the length of hospitalization of the patients. Conclusions: These results suggest that MIS-C has a significant effect on repolarization, which could lead to lethal arrhythmia, including QT prolongation and ventricular tachycardia. These ECG changes may be strongly related to the prognosis and could help physicians decide which patients might have the risk of lethal arrhythmias.

Value of q waves in lateral and left precordial leads in patients with left bundle branch block to predict the response to cardiac resynchronizationtherapy.

The cardiac resynchronization therapy (CRT) non-response rate can reach 30% in heart failure (HF) patients with left bundle branch block (LBBB). This study aimed to evaluate the value of baseline q waves in leads I, V5, or V6 in predicting response to CRT in patients with HF and LBBB. Patients with HF (left ventricular ejection fraction ≤35%) and LBBB receiving CRT implantation were retrospectively enrolled. Baseline characteristics and electrocardiogram parameters, including lateral and left precordial q waves were evaluated. Non-response to CRT was defined as the improvement of left ventricular ejection fraction (LVEF)<5% at a 6-month follow-up. A total of 132 patients (mean age 63.0±10.4 years, 94 [71.2%] male) were included. Among them, 32 patients with q waves in leads I, V5, or V6 were classified into the qLBBB (+) group, and the rest without q waves in these leads were defined as the qLBBB (-) group. The CRT non-response rate in the qLBBB (+) group was markedly higher than that in the qLBBB (-) group (68.8%vs. 33.3%, p<.001). Multivariable logistic regression analysis revealed that the presence of baseline q waves in leads I, V5, or V6 remained significantly associated with a higher rate of CRT non-response in patients with HF and LBBB (odds ratio: 4.8, 95% confidence interval: 1.5-15.0, p=.007). Any q wave in leads I, V5, or V6 was an independent predictive factor for CRT non-response in patients with HF and LBBB.

Clinical and genetic characteristics of catecholaminergic polymorphic ventricular tachycardia combined with left ventricular non-compaction.

Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype. Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V. The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues. Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.

A tutorial for model-based evaluation and translation of cardiovascular safety in preclinical trials.

Assessment of drug-induced effects on the cardiovascular (CV) system remains a critical component of the drug discovery process enabling refinement of the therapeutic index. Predicting potential drug-related unintended CV effects in the preclinical stage is necessary for first-in-human dose selection and preclusion of adverse CV effects in the clinical stage. According to the current guidelines for small molecules, nonclinical CV safety assessment conducted via telemetry analyses should be included in the safety pharmacology core battery studies. However, the manual for quantitative evaluation of the CV safety signals in animals is available only for electrocardiogram parameters (i.e., QT interval assessment), not for hemodynamic parameters (i.e., heart rate, blood pressure, etc.). Various model-based approaches, including empirical pharmacokinetic-toxicodynamic analyses and systems pharmacology modeling could be used in the framework of telemetry data evaluation. In this tutorial, we provide a comprehensive workflow for the analysis of nonclinical CV safety on hemodynamic parameters with a sequential approach, highlight the challenges associated with the data, and propose respective solutions, complemented with a reproducible example. The work is aimed at helping researchers conduct model-based analyses of the CV safety in animals with subsequent translation of the effect to humans seamlessly and efficiently.

Diagnostic performance of machine learning on 12-lead electrocardiogram for predicting multi-vessel coronary vasospastic angina

Abstract Background Multi-vessel coronary vasospastic angina (multi-VSA) is life-threatening disease. However, 12-leads electrocardiogram (ECG) in no chest symptom period was considered to have no predictive value for the multi-VSA. We tried to predict multi-VSA by machine learning (ML) on parameters of the 12-lead electrocardiogram. Purpose To predict multi-VSA by machine learning on ECG parameters in no chest pain period. Methods We recruited 227 consecutive sinus-rhythm patients (63.6±12.9years, 136men) who underwent acetylcholine-provocation test in coronary angiography (CAG). Multi-VSA was defined as spasm in at least 2 major branches which was provoked by ACh. ECG was recorded before CAG in no chest pain period. ML was performed on table data of ECG parameters (ex. ST level ant J point, R wave amplitude, and/or J wave in each lead) using several ensemble learning methods. Results 79 patients (35%) showed multi-VSA, and the breakdown of the multi-VSA was as follows: double vessel 44, triple vessel 35, including LAD 73, LCx 47, RCA73. Univariate logistic regression analysis extracted 23 significant but weak predictors, the highest area under receiver operating characteristics curve (AUROC) was 0.673 of Q wave amplitude in lead aVL. Conversely, ML demonstrated high diagnostic performance (AUROC of extra trees classifier: 0.817). Shapley additive explanation method in the extra trees showed male, QTc, J wave in lead II, and low amplitude of Q wave in lead I/aVL played essential roles to build the ML model. Conclusion Several parameters of 12-lead ECG in multi-VSA patients contains potential features of VSA, and their aggregation and ensemble learning can predict VSA with high diagnostic performance.

Clustering by artificial intelligence for multi-vessel coronary artery disease on electrocardiography gated single photon emission computed tomography

Abstract Backgrounds Diagnosis of multi-vessel coronary artery disease (MVD) on single photon emission computed tomography (SPECT) is recognized to be difficult. We tried to classify patients who were suspected coronary artery stenosis by artificial intelligence (AI) clustering on parameters of electrocardiogram (ECG) gated SPECT (gated-SPECT), and evaluated their predictive value for MVD. Methods We enrolled consecutive 335 patients (median:74years [68, 79], 255man) who underwent adenosine stress ECG gated-SPECT and coronary angiography in 3-months. No sinus rhythm patients were excluded. MVD was defined as at least two main branch coronary artery stenosis whose fractional flow reserve over 0.80 which was evaluated by coronary angiography. Univariate logistic regression analysis extracted significant predictors among many paremeters of the SPECT (summed score, left ventricular (LV) volume, systolic and diastolic function, and degree of LV dyssynchrony), and using them, AI clustering (K-means) was performed. Results Breakdown of MVD was as follows: MVD was 48 (double vessel disease 30, LMT stenosis 5, and triple vessel 13). Single vessel disease was 91, and no lesion was 196 cases. Clustering was performed using 21 significant parameters of the SPECT and clinical characteristics (Diabetes, LVEF, heart rate(HR), SD-TES, MDSV, 1/3 mean filling rate, peak filling ratio on adenosine stress, LVEF, HR, SD-TES, MDSV at rest, and other 10 predictors). Number of clusters was set as 4 by elbow plotting method. Prevalence of MVD was significantly different in the 4 clusters (Odds ratio: Cluster B/C/D to A, 3.05/3.61/6.60, respectively). Compared with cluster A, clusteter B/C/D showed increased summed stress score, chronic kidney disease, SD-TES (=left ventricular end-systolic dyssynchrony parameter) on stress, decreased left ventricular ejection fraction and 1/3 mean filling rate. Conclusions AI clustering on gated-SPECT had powerful predictive value for MVD.

Maternal hypertensive disorders of pregnancy and electrocardiographic findings in newborns

Abstract Background Hypertensive disorders of pregnancy (HDP) - preeclampsia in particular - are important causes of pregnancy complications and death for both the mother and her offspring. Preeclampsia is also associated with both congenital heart defects (CHDs) in the offspring and subtle changes in left ventricular structure and function in the offspring. However, whether preeclampsia also affects the newborn’s cardiac conduction system is unknown. Purpose To assess whether newborns born after pregnancies complicated by HDP exhibit changes in their electrocardiogram (ECG) compared with newborns born after pregnancies without HDP. Methods This population-based cohort study included newborns, who had ECG data obtained within 30 days of birth. Information on maternal preeclampsia (ICD-10 codes DO14-14.2 and DO15-15.9) and maternal gestational hypertension (ICD-10 codes DO13-13.9) was retrieved from an obstetric database. ECG parameters of interest included heart rate, PR interval, QRS axis, QRS duration, uncorrected and corrected QT intervals, maximum R- and S-wave amplitudes in V1 and V6, respectively. ECG parameters of exposed and non-exposed newborns were compared using summary statistics and linear regression, adjusting for sex, gestational age at delivery and length, weight and age at examination. Sensitivity analyses were conducted with adjustments for maternal smoking, parity, age, and multiple pregnancies and the analyses were repeated after excluding neonates and mothers with CHD, newborns exposed to pre-gestational diabetes and children born preterm (&amp;lt;37 weeks’ gestation). Results Our study cohort included 11,826 newborns; 441 were exposed to maternal preeclampsia and 320 were exposed to maternal gestational hypertension (table). Newborns born to mothers with preeclampsia had significantly prolonged QRS duration compared to neonates born after pregnancies without HDP (adjusted mean difference of 0.6 ms, 95% CI [0.04 – 1.16], p=0.04). The maximum amplitude of the R-wave in the V1-recording was significantly lower in newborns born to mothers with preeclampsia by 5% (linear scale: 0.95, 95% CI [0.9 – 0.996], p=0.03). These associations persisted after adjustment for additional covariates and restrictions on the study population. Gestational hypertension was not associated with significant differences in any of the investigated ECG parameters. Conclusion The cardiac conduction was affected in children born to mothers with preeclampsia compared with newborns born after pregnancies without HDP, including prolonged QRS duration and lower amplitude of the R-wave in V1 in the ECG. These findings could be an indicator of thickening of the left ventricular myocardium in newborns of mothers with preeclampsia. The potential clinical implications of these changes – short or long-term – are unknown and require further investigation.Table