Changes In Ventricular Repolarization Research Articles

Beat-to-beat cardiac repolarization lability increases during hypoxemia and arousals in obstructive sleep apnea patients.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly (P < 0.01), whereas QTVI decreased (P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified (P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β = 0.405, P < 0.01), STVQT (β = 0.151, P < 0.01), and QTVI (β = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep.NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.

Iso-osmolar vs low-osmolar contrast agents for coronary optical coherence tomography: a blinded prospective randomized controlled study.

The impact of contrast type on coronary optical coherence tomography (OCT) imaging has received limited research. We conducted a blinded, prospective, single-center, randomized, controlled crossover study comparing iso-osmolar contrast media (IOCM) with low-osmolar contrast media (LOCM) in patients undergoing clinically indicated coronary OCT imaging. Patients were randomly assigned to undergo OCT imaging with either IOCM or LOCM as the initial contrast medium. Following a washout period, a second run of OCT imaging of the same coronary vessel was performed using the other contrast medium. A total of 62 patients were randomized to IOCM first (n = 31) or LOCM first (n = 31). Mean patient age was 65.9 ± 11.2 years and 74.2% were male, with high prevalence of dyslipidemia (82.3%) and prior myocardial infarction (41.9%). Percutaneous coronary intervention was performed in 60 cases (96.8%) and the left anterior descending artery was the most common target vessel (53.3%). The contrast volume used for OCT imaging was similar for IOCM and LOCM (8.0 [6.9, 9.0] mL vs 8.0 [6.7, 9.0] mL; P = .89), as was the length of clear OCT images (70.0 [62.8, 74.0] mm for IOCM vs 70.0 [64.0, 74.0] mm for LOCM; P = .65). Electrocardiographic changes were observed in 11 runs with IOCM (ventricular repolarization changes in 9 runs and premature ventricular contractions [PVCs] in 2 runs) vs 12 runs with LOCM (ventricular repolarization changes in 9 runs and PVCs in 3 runs). The use of IOCM in coronary OCT is associated with similar contrast volume and clear imaging length when compared with LOCM.

Flavoring Agents in E-cigarette Liquids: A Comprehensive Analysis of Multiple Health Risks.

The availability of a wide range of flavored e-cigarettes is one of the primary reasons for vaping initiation and persistent use among adolescents and young people. This plethora of flavors available on the market are crafted using different flavoring agents such as cinnamaldehyde, vanillin, benzaldehyde, ethyl maltol, menthol, and dimethylpyrazine. Recent studies have brought to light the potential risks associated with e-cigarette flavoring agents and their effects on various organ systems, both with and without nicotine. Research has demonstrated that flavoring agents can induce inflammation, endothelial dysfunction, epithelial barrier disruption, oxidative stress, DNA damage, electrophysiological alterations, immunomodulatory effects, and behavioral changes, even independently of nicotine. Notably, these negative outcomes adversely affect cardiovascular system by reducing cell viability, decreasing endothelial nitric oxide synthase, nitric oxide bioavailability, soluble guanylyl cyclase activity and cyclic guanosine monophosphate accumulation, impairing endothelial proliferation and tube formation, and altering vasoreactivity resulting in vascular dysfunction. In the heart, these agents decrease parasympathetic activity, induce depolarization of resting membrane potential, loss of rhythmicity, increase isovolumic relaxation time, and change in ventricular repolarization and ventricular tachyarrhythmias. It is found that the specific response elicited by flavoring agents in different organ systems varies depending on the flavor used, the concentration of the flavoring agent, and the duration of exposure. However, the literature on the effects of flavoring agents is currently limited, emphasizing the need for more preclinical and randomized clinical trials to gain a deeper understanding and provide further evidence of the harmful effects of flavored e-cigarette use. In summary, recent research suggests that flavoring agents themselves can have detrimental effects on the body. To fully comprehend these effects, additional preclinical and clinical studies are needed to explore the risks associated with flavored e-cigarette usage.

Investigation of QT Dispersion and T-Peak to T-End/Corrected QT Ratio in Multisystem Inflammatory Syndrome in Children.

Introduction Multisystem inflammatory syndrome in children (MIS-C) is characterized by hyperinflammation, heart involvement, and multiorgan failure, which develop following coronavirus disease 2019. Ventricular arrhythmias have been identified during this syndrome. It is known that the risk of ventricular arrhythmia is associated with ventricular repolarization changes. The aim of this study was to investigate the corrected QT interval, QT dispersion, T wave peak-to-end interval, and T-peak to T-end/corrected QT ratio in MIS-C. Methods The study included 35 patients diagnosed with MIS-C and 35 subjects as the control group. The ventricular diameters, ejection fraction, valve insufficiency, and coronary artery were examined in both groups using echocardiography. Corrected QT interval, QT dispersion, T wave peak-to-end interval, and T-peak to T-end/corrected QT ratio were determined by 12-lead electrocardiogram. Results The patient group had increased corrected QT interval (p<0.05), QT dispersion (p = 0.001), T-peak to T-end interval (p=0.001), and T-peak to T-end/corrected QT ratio (p = 0.001) compared to the control group. Moreover, there was a correlation between increased QT dispersion, T-peak to T-end, T-peak to T-end/corrected QT ratio, and decreased ejection fraction (r = -0.51 and p = 0.001, r = -0.71 and p < 0.001, r = -0.69 and p < 0.001, r = -0.56 and p < 0.001, respectively). Conclusions Our study demonstrated increased QTc interval, QT dispersion, T-peak to T-end interval, T-peak to T-end/corrected QT ratio in MIS-C. This result may indicate an increased risk of ventricular arrhythmia for these patients.

0441 Positive airway pressure therapy associated changes in ventricular repolarization in patients with heart failure

Abstract Introduction Obstructive sleep apnea (OSA) is associated with prolonged ventricular repolarization at baseline that further increases during sleep when an apnea/hypopnea event occurs. Aggressive treatment of OSA with positive airway pressure therapy (PAP) may further prolong ventricular repolarization during apnea/hypopnea events particularly in patients with heart failure (HF). The goal of this study was to evaluate how ventricular repolarization changes during apnea/hypopnea events in patients with heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction and in those patients without HF. Methods Thirty patients with OSA in each of the following groups were randomly selected from a dataset of 2,817 patients: HFrEF, HFpEF and no HF failure. Overnight polysomographies (PSG) for these patients were reviewed and beat-to beat measurements during apnea/hypopnea events were obtained at baseline (without PAP) and on the highest PAP setting attempted. Fridericia’s heart rate corrections were used to calculate QTc. QT variability was measured as the standard deviation of QT intervals (SDQT). Results The electrocardiogram was analyzable for n=11 with HFrEF (age 71± 17 years , 91% male) , n=28 with HFpEF (age 71± 12 years , 43% male) and n=30 without HF (age 57± 12 years , 50% male). In those with HFrEF, the mean (SD) QTc increased from 442(12)ms to 452(13)ms and SDQT increased from 9(2) to 13 (2) from baseline to the highest level of PAP attempted. In those with HFpEF, the mean (SD) QTc decreased from 448 (8) to 436 (8) ms and SDQT increased from 10 (1) to 11 (1) from baseline to the highest level of PAP attempted. In those without HF, the mean (SD) QTc increased from 429(37) to 439(56) and SDQT was stable from 8(6) to 8(8) from baseline (no PAP) to the highest level of PAP attempted. There were significant differences noted between the groups in changes in QTc (p=0.002) and SDQT (p=0.048) on PAP when compared to baseline. Conclusion Patients with HFrEF had increases in both QTc and SDQT with PAP at high pressures placing them at greater risk for ventricular arrhythmias. Support (if any) AASM Foundation (203-JF-18), NIH (HL126140, 2L30HL154400-023), University of Arizona (5299903; 5833261; 4258021)

P226 A STRANGE CASE OF ISOLATED RIGHT VENTRICULAR DYSFUNCTION

Abstract Introduction In Europe, approximately 29% of the population aged between 15 and 64 have used illicit drugs. Italy is at the top of this ranking. Description 45–year–old female, no previous cardiology events. She enters the Emergency Department for typical chest pain following alcohol and cocaine abuse. EKG (see figure 1) detects sinus tachycardia and mild non–specific changes in ventricular repolarization. Blood tests reveal an increase in Troponin T levels (305 ng/L, NV &amp;lt; 14 ng/L, then decreased with subsequent measurements) and D–dimer (902 mg/mL, NV &amp;lt; 500 mg/mL). Echocardiography reveals a non–dilated right ventricle with severe systolic dysfunction (TAPSE 11 mm). No signs of pulmonary hypertension but a dilated and hypocollapsing inferior vena cava is noted. Abnormal motion of the interventricular septum with systolic d–shape is present (see figure 2). Left ventricle appears normal. Pulmonary angio–Tc was negative for embolic phenomena and coronary angiography detects no lesions on coronary arteries. At discharge, right ventricular systolic dysfunction and septal d–shape were completely regressed (see Figure 3). Discussion Cocaine is a strong systemic adrenergic agonist, which can cause vasospasm of small arterioles of the cardiac microcirculation with possible formation of intracoronary thrombi. Peculiarity of this case is the selective and reversible involvement of the right ventricle, an extremely rare presentation as evidenced by the almost absence of scientific literature on the subject (there is only a similar case report published on the American Journal of Emergency Medicine in 2015). Reversible damage from vasospasm and/or intracoronary thrombosis localized to the marginal branch of the right coronary artery, induced by cocaine use, is conceivable. D–shape of the interventricular septum associated with right ventricular dilatation is likely caused by acute right ventricular failure causing volume overload in the right sections. Take home message Drugs abuse is a widespread problem among the population. Cocaine intake is associated with important adverse cardiovascular effects. A rare presentation can be isolated right ventricular ischemia associated with acute right heart failure.

C31 NEXT GENERATION MYOCARDITIS

Abstract A 75–year–old overweight man, affected by hypertension, diabetes mellitus and atrial fibrillation since 2020. After 3 unsuccessful attempts of electrical cardioversion it was opted for a strategy of rate control with beta blocker and anticoagulant therapy with Rivaroxaban 20 mg. Following episodes of rectal bleeding; adenocarcinoma of the colon was diagnosed. The patient underwent hemicolectomy and started therapy with Pembrolizumab. The anticoagulant was replaced with Edoxaban 60 mg. In August 2022, he was admitted to the emergency department for severe signs and symptoms of heart failure. On ECG, atrial fibrillation with a heart rate of 90 bpm and non–specific changes in ventricular repolarization. The echocardiogram showed a severe reduction of the ejection fraction (FE 30%), which was not present at previous controls. On blood tests, troponins were negative and BNP increased. The patient underwent coronarography which was negative for significant lesions, and heart failure therapy was prescribed. Three months later the patient came to our cardio–oncology outpatient clinic; we repeated the echocardiogram which showed a recovery of the ejection fraction to 45% and planned a cardiac MRI. Cardiac MRI (CMR) showed global left ventricular hypokinesia (FE 42%) and late subepicardial gadoline enhancement in the basal segment of the inferior wall and transmural in the basal segment of the lateral wall without signs of oedema. Report described as compatible with myocarditis. The case was discussed collegially with radiologists and oncologists, and it was decided to discontinue immunotherapy (ICI). Myocarditis is the most common cardiovascular adverse events of ICI therapy, although it has a very low incidence. Generally, myocarditis related to ICI therapy has a high mortality rate and requires discontinuation of ICI. In addition, CMR may have a lower sensitivity in this setting. There is also a possibility of developing left ventricular dysfunction without associated myocarditis in the absence of increase in cardiac troponin and active myocardial inflammation at CMR. Although our case has been defined as myocarditis, it presents some unclear aspects due in part to the early non–diagnosis as a complication of ICI therapy. Although cancer patients taking ICI has expanded considerably in recent years, the evidence on cardiovascular complications is scarce and unknown to the clinical cardiologist.

C79 NEGATIVE T WAVES ON ECG: NOT JUST HYPERTROPHIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic cardiomyopathy is still considered a rare and difficult–to–diagnose condition, yet a well–founded clinical–instrumental suspicion and proper diagnostic procedure can unveil this condition early from common instrumental findings. Clinical Case In September, a 34–year–old man presented to our center for the presence on the electrocardiogram of ventricular repolarization changes (negative T waves in D1, inferior site and in all precordial leads with mild ST elevation in V1– V2). He denied family history of cardiological events. In 2018, following a suspected preoperative EKG, he performed an echocardiogram and cardiac magnetic resonance imaging (CMR); these examinations showed mild left ventricular hypertrophy with preserved systolic function. Clinically, the patient reported rare episodes of palpitation presented on ambulatory EKG with the same repolarization changes as mentioned above. In consideration of the clinic–instrumental findings, a diagnostic workup with echocardiogram and CMR was started for suspicion of hypertrophic cardiomyopathy in the first hypothesis. On echocardiogram, an non dilated left ventricle was found with left ventricular ejection fraction, parietal thicknesses, and segmental kinetics within normal limits, in the absence of significant valvulopathy; however, frequent ventricular extrasystoles were reported during the examination. Given the EKG–graphic alterations, although there weren‘t any echocardiographic changes, a CMR was performed, showing extensive irregularity of the epicardial profile of the lateral and infero–lateral mid–apical wall, site of adipose infiltration, in which evidence of intramyocardial late gadolinium enhancement (LGE) was also present; the right ventricle showed extensive microbulging of the mid–basal free wall in the absence of adipose replacement or LGE. In view of the clinical–instrumental pattern, the diagnosis of "left dominant" arrhythmogenic cardiomyopathy with initial involvement of the right ventricle was made. Conclusions EKG–graphic interpretation may in some cases be the only instrumental data underlying clinical suspicion of arrhythmogenic cardiomyopathy, allowing early diagnosis of a condition at high risk of sudden cardiac death.

CineECG for visualization of changes in ventricular activation and repolarization during ischemia

High-intensity focused ultrasound (HIFU) can achieve accurate and focused deep tissue ablation through an extracorporeal emission. Cardiac ablation using HIFU applied transthoracically must overcome potential interference from intervening thoracic structures. The aim of this study was to explore the efficacy and safety of septal ablation that was induced using transthoracic HIFU.Twenty-one canines were pretreated to improve acoustic transmission. Single ablations were induced by targeting transthoracic HIFU with acoustic power of 400 W for 3 sec at the middle and basal septum in eight canines. Extended ablations were performed to create larger lesions at the basal septum in eight more canines. The three-dimensional morphology of a basal septum lesion induced by a single ablation was analyzed. The temperature at the ablative targets was measured in the other five canines.The cardiomyocytes in the lesions underwent necrosis with a clear boundary. The three-dimensional morphology of the lesions appeared approximately as ellipsoids with a flatter endocardial side. The peak temperature at a power of 400 W for 3 sec was 93.27 ± 2.54°C, and it remained >50°C for nearly 10 sec. No procedure-related complications were observed.Ultrasound-guided transthoracic HIFU has the potential to safely create small dot or large mass lesions in the septum without a thoracotomy or a catheter.

COMPLETA RECUPERAÇÃO PÓS-COVID-19 GRAVE EM PACIENTE COM MUCOPOLISSACARIDOSE TIPO 2

INTRODUCTION: Children with comorbidities are at greater risk of developing severe forms of Covid-19. This paper reports a case of Mucopolysaccharidosis Type 2 (MPS-II) that presented complete recovery after severe Covid-19. CASE DESCRIPTION: Male, 13 years old, with MPS-II, is seen in a pediatric emergency room due to respiratory distress, airway hypersecretivity and fever. On physical examination, he had room air desaturation, snoring and diffuse coarse rales on pulmonary auscultation. Laboratory tests revealed: rod-like cell count, cytoplasmic vacuolization in neutrophils, thrombocytopenia, consumption coagulopathy, toxic level of valproic acid, respiratory acidosis and metabolic alkalosis; in addition to positivity for Covid-19. Chest radiography showed perihilar infiltrate with retrocardiac consolidation. Computed tomography of the chest showed bilateral perihilar and basal consolidations, in addition to bilateral endobronchial dissemination. Electrocardiogram showed changes in ventricular repolarization and ST-segment depression. Thus, Covid-19 infection was diagnosed, with secondary bacterial pneumonia and hemodynamic and cardiac repercussions, concomitant valproic acid intoxication. The patient required intensive care for 22 days, mechanical ventilation support for 19 days, in addition to the use of vasoactive drugs. He was discharged from hospital after 49 days, with gastrostomy, tracheostomy and home oxygen. COMMENTS: MPS-II carriers tend to have most severe form and worse prognosis when infected with Covid-19. This is because there are factors inherent to MPS-II that make it difficult to recover after pulmonary infections, such as: previous pulmonary dysfunction, macroglossia, adenoid hypertrophy, hypersecretivity and hypotonia. Such factors reflect the long hospital stay of patient reported when they get Covid-19.

Study an elderly people's abnormal electrocardiographic changes at government hospital

Population aging is one of the demographic characteristics of the 21st century. This process is necessarily accompanied by an increase in the prevalence of cardiovascular diseases that may have expression on the electrocardiogram (ECG). Aim: to study an elderly people's abnormal electrocardiograph at government hospital. Material and Methods:All the Patients were admitted in the department of Medicine at Government medical college, Kadapa, Andhra Pradesh, India. Study period January 2021 to june 2021These participants were then clinically examined and studied in accordance with the study's guidelines to generate the necessary data, which was then categorised, tabulated, and classed before being subjected to analysis. Total 300 persons should taken in the study.150 were healthy one and 150 were patients. The age of the persons should be 65 years and above, both the sex were included. Conclusion: Atrial fibril-lation was the most prevalent rhythm abnormality. With no association to sex or skin tone, ventricular repolarization changes outweighed ventricular depolarization changes. There were a sizable number of instances with extended QT, left ventricular hypertrophy, and anomalous left atrium.

Synchronization of repolarization after cardiac resynchronization therapy: A combined clinical and modeling study.

IntroductionThe changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. This knowledge gap is addressed using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and using patient‐specific computational modeling.MethodsIn 33 patients electrocardiographic and echocardiographic measurements were performed before and at various intervals after CRT, both during CRT‐ON and temporary CRT‐OFF. T‐wave area was calculated from vectorcardiograms, and reconstructed from the 12‐lead electrocardiography (ECG). Computer simulations were performed using a patient‐specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, fit to a patient's ECG.ResultsDuring CRT‐ON T‐wave area diminished within a day and remained stable thereafter, whereas QT‐interval did not change significantly. During CRT‐OFF T‐wave area doubled within 5 days of CRT, while QT‐interval and peak‐to‐end T‐wave interval hardly changed. Left ventricular (LV) ejection fraction only increased significantly increased after 1 month of CRT. Computer simulations indicated that the increase in T‐wave area during CRT‐OFF can be explained by changes in APD following chronic CRT that are opposite to the change in CRT‐induced activation time. These APD changes were associated with a reduction in LV dispersion in repolarization during chronic CRT.ConclusionT‐wave area during CRT‐OFF is a sensitive marker for adaptations in ventricular repolarization during chronic CRT that may include a reduction in LV dispersion of repolarization.

Synchronization of repolarization after cardiac resynchronization therapy: time course and relation to reverse remodeling

Abstract Funding Acknowledgements Type of funding sources: None. Background The changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. Objective Address this knowledge gap using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and patient-specific computational modeling. Methods In a cohort of consecutive CRT patients, electrocardiographic and echocardiographic measurements were performed before and at various intervals after CRT, both during CRT-ON and temporary CRT-OFF. T-wave area was calculated from vectorcardiograms, reconstructed from the 12-lead ECG. Computer simulations were performed using a patient-specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, based on a patient’s ECG and MRI-based chest and cardiac anatomy. Results In 33 patients T-wave area during CRT-OFF doubled within 5 days of CRT (left figure) while other repolarization markers like QT-interval and peak-to-end T-wave interval hardly changed. Patients with T-wave area increase above the median increase showed a significantly larger increase in left ventricular ejection fraction than those with smaller T-wave area increase (+11±8% vs. +6±6%, respectively; p&amp;lt;0.05, n=76). Computer simulations (figure, right) show the sequence of depolarization and repolarization before CRT, obtained by the patient-specific model (BL LBBB) and following Acute CRT. Repolarization after chronic CRT-OFF was obtained by matching the measured CRT-OFF ECG with that provided by the model. The best match was obtained by changes in APD following chronic CRT that are opposite to the change in CRT-induced activation time. Such APD changes were associated with a reduction in right and left ventricular dispersion in repolarization during chronic CRT-ON compared with acute CRT-ON. Conclusions T-wave area during CRT-OFF is a sensitive marker for adaptations in ventricular repolarization after CRT that are related to CRT-induced reverse remodeling and may involve an inverse relation between activation time and APD, coinciding with lower right and left ventricular dispersion of repolarization and with larger increases in LV ejection fraction during chronic CRT.

Screening for QTc prolongation during acute exercise in childhood acute lymphoblastic leukemia survivors

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Institute of Cancer Research (ICR) of the Canadian Institutes ofHealth Research (CIHR), C17 Council Background Anthracycline-related cardiotoxicity is a major cause of mortality and morbidity in childhood acute lymphoblastic leukaemia (ALL) survivors. Electrophysiologic complications and cardiac autonomic dysfunction are both known to be developed by childhood ALL survivors. Current methods for detection of cardiotoxicity have limitations, particularly due to their lack of sensitivity for early detection of subclinical cardiac dysfunction. Early detection of cardiac dysfunction remains a cardiologist’s challenge and is essential to allow optimal therapeutic intervention. Purpose This study aimed to observe ventricular repolarization during a maximal cardiopulmonary exercise test (CPET) in childhood ALL survivors. We hypothesized that cancer treatments lead to changes in ventricular repolarization that persist over time, and that the use of CPET allows the unmasking of electrophysiological abnormalities. Methods A total of 250 childhood ALL survivors underwent a maximal CPET on an ergocycle, and their direct oxygen uptake was measured. All survivors were monitored continuously during the test using a 12-lead electrocardiogram. Measurements of the QT interval were completed at rest, at the end of each stage of the CPET, and during recovery. The QT interval was defined as the period from the onset of the Q-wave to the end of the T-wave, measured linearly. Values were corrected (QTc) using a specific group equation. To compare the effect of cardiorespiratory fitness on QTc during CPET, participants were divided in two groups according to the median of survivors’ cardiorespiratory fitness (group A: &amp;lt;32.0 mL.kg-1.min-1; group B: ≥32.0 mL.kg-1.min-1). Results All survivors (median age: 21 years, 51.5% male) included in the final analysis (n=200) performed a validated maximal CPET. At rest, the QTc interval was 379.1±32.2ms. None of the participants had a prolonged QTc during exercise (371.5±16.1ms, range 310.7-416.1ms). The mean QTc interval during CPET was not different between groups A and B (370.1±17.6ms and 373.0±14.4ms, p=0.218). Group A had a longer QT interval at low to moderate exercise intensities. During recovery, the QTc interval was 373.4.1±16.2ms. Conclusions Cancer and anthracycline treatments have an impact on the cardiorespiratory system. Low cardiorespiratory fitness in childhood ALL survivors is associated with longer ventricular repolarization during exercise. These differences may be an indicator of altered cardiac function. This shows the importance of studying the response to exercise to improve early cardiac dysfunction detection, as well as documenting the autonomic nervous system response to exercise between survivors with lower and higher physical fitness.

Investigation of the Effects of the Short QT Syndrome D172N Kir2.1 Mutation on Ventricular Action Potential Profile Using Dynamic Clamp.

The congenital short QT syndrome (SQTS) is a cardiac condition that leads to abbreviated ventricular repolarization and an increased susceptibility to arrhythmia and sudden death. The SQT3 form of the syndrome is due to mutations to the KCNJ2 gene that encodes Kir2.1, a critical component of channels underlying cardiac inwardly rectifying K+ current, IK1. The first reported SQT3 KCNJ2 mutation gives rise to the D172N Kir2.1 mutation, the consequences of which have been studied on recombinant channels in vitro and in ventricular cell and tissue simulations. The aim of this study was to establish the effects of the D172N mutation on ventricular repolarization through real-time replacement of IK1 using the dynamic clamp technique. Whole-cell patch-clamp recordings were made from adult guinea-pig left ventricular myocytes at physiological temperature. Action potentials (APs) were elicited at 1 Hz. Intrinsic IK1 was inhibited with a low concentration (50 µM) of Ba2+ ions, which led to AP prolongation and triangulation, accompanied by a ∼6 mV depolarization of resting membrane potential. Application of synthetic IK1 through dynamic clamp restored AP duration, shape and resting potential. Replacement of wild-type (WT) IK1 with heterozygotic (WT-D172N) or homozygotic (D172N) mutant formulations under dynamic clamp significantly abbreviated AP duration (APD90) and accelerated maximal AP repolarization velocity, with no significant hyperpolarization of resting potential. Across stimulation frequencies from 0.5 to 3 Hz, the relationship between APD90 and cycle length was downward shifted, reflecting AP abbreviation at all stimulation frequencies tested. In further AP measurements at 1 Hz from hiPSC cardiomyocytes, the D172N mutation produced similar effects on APD and repolarization velocity; however, resting potential was moderately hyperpolarized by application of mutant IK1 to these cells. Overall, the results of this study support the major changes in ventricular cell AP repolarization with the D172N predicted from prior AP modelling and highlight the potential utility of using adult ventricular cardiomyocytes for dynamic clamp exploration of functional consequences of Kir2.1 mutations.

The 2020 "Padua Criteria" for Diagnosis and Phenotype Characterization of Arrhythmogenic Cardiomyopathy in Clinical Practice.

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria (“the Padua criteria”) were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice.

Catecholamines are key modulators of ventricular repolarization patterns in the ball python (Python regius).

Ectothermic vertebrates experience daily changes in body temperature, and anecdotal observations suggest these changes affect ventricular repolarization such that the T-wave in the ECG changes polarity. Mammals, in contrast, can maintain stable body temperatures, and their ventricular repolarization is strongly modulated by changes in heart rate and by sympathetic nervous system activity. The aim of this study was to assess the role of body temperature, heart rate, and circulating catecholamines on local repolarization gradients in the ectothermic ball python (Python regius). We recorded body-surface electrocardiograms and performed open-chest high-resolution epicardial mapping while increasing body temperature in five pythons, in all of which there was a change in T-wave polarity. However, the vector of repolarization differed between individuals, and only a subset of leads revealed T-wave polarity change. RNA sequencing revealed regional differences related to adrenergic signaling. In one denervated and Ringer's solution-perfused heart, heating and elevated heart rates did not induce change in T-wave polarity, whereas noradrenaline did. Accordingly, electrocardiograms in eight awake pythons receiving intra-arterial infusion of the β-adrenergic receptor agonists adrenaline and isoproterenol revealed T-wave inversion in most individuals. Conversely, blocking the β-adrenergic receptors using propranolol prevented T-wave change during heating. Our findings indicate that changes in ventricular repolarization in ball pythons are caused by increased tone of the sympathetic nervous system, not by changes in temperature. Therefore, ventricular repolarization in both pythons and mammals is modulated by evolutionary conserved mechanisms involving catecholaminergic stimulation.

Timing of food intake in mice unmasks a role for the cardiomyocyte circadian clock mechanism in limiting QT-interval prolongation

ABSTRACT Cardiac electrophysiological studies demonstrate that restricting the feeding of mice to the light cycle (time restricted feeding or TRF) causes a pronounced change in heart rate and ventricular repolarization as measured by the RR- and QT-interval, respectively. TRF slows heart rate and shifts the peak (acrophase) of the day/night rhythms in the RR- and QT-intervals from the light to the dark cycle. This study tested the hypothesis that these changes in cardiac electrophysiology are driven by the cardiomyocyte circadian clock mechanism. We determined the impact that TRF had on RR- and QT-intervals in control mice or mice that had the cardiomyocyte circadian clock mechanism disrupted by inducing the deletion of Bmal1 in adult cardiomyocytes (iCSΔBmal1 −/− mice). In control and iCSΔBmal1 −/− mice, TRF increased the RR-intervals measured during the dark cycle and shifted the acrophase of the day/night rhythm in the RR-interval from the light to the dark cycle. Compared to control mice, TRF caused a larger prolongation of the QT-interval measured from iCSΔBmal1 −/− mice during the dark cycle. The larger QT-interval prolongation in the iCSΔBmal1 −/− mice caused an increased mean and amplitude in the day/night rhythm of the QT-interval. There was not a difference in the TRF-induced shift in the day/night rhythm of the QT-interval measured from control or iCSΔBmal1 −/− mice. We conclude that the cardiomyocyte circadian clock does not drive the changes in heart rate or ventricular repolarization with TRF. However, TRF unmasks an important role for the cardiomyocyte circadian clock to prevent excessive QT-interval prolongation, especially at slow heart rates.

Evaluation of Tp-e interval, Tp-e/QT ratio and index of cardiac-electrophysiological balance in patients with tinnitus

BackgroundTinnitus is a common auditory symptom. Dysfunction in the autonomic nervous system (ANS) is an essential part of the etiopathogenesis of tinnitus. ANS regulates heart rate and heart rhythm and can lead to ventricular repolarization changes, which can cause malignant ventricular arrhythmias. T wave peak-to-end T(p-e) interval and T(p-e)/QT ratio are known ventricular arrhythmia indexes, and the index of cardiac-electrophysiological balance (iCEB) is a novel index that can be used to predict the risk of malignant ventricular arrhythmia. The goal of the study was to investigate these ventricular arrhythmia indexes in patients with tinnitus.MethodsThe study population consisted of 240 patients with tinnitus and 240 healthy subjects. A standard 12-channel surface electrocardiogram was applied to both groups. T(p-e) interval, QT interval and QRS duration were determined. Corrected QT (QTc) was determined via Bazett’s formula. To predict ventricular arrhythmia, iCEB (QT/QRS), T(p-e)/QT, corrected iCEB (QTc/QRS) and T(p-e)/QTc values were determined and compared between groups.ResultsCompared to the control group, QT (376.46 ± 36.54 vs 346.52 ± 24.51 ms), QTc (426.68 ± 24.68 vs 390.42 ± 24.04 ms), T(p-e) (75.86 ± 14.68 vs 62.42 ± 8.64 ms), T(p-e)/QT (0.201 ± 0.06 vs 0.180 ± 0.01) and T(p-e)/QTc (0.177 ± 0.06 vs 0.159 ± 0.02) were significantly higher in patients with tinnitus (p < 0.001 for all). QT/QRS (3.92 ± 0.68 vs 3.56 ± 0.32) and QTc/QRS (4.44 ± 1.03 vs 4.01 ± 0.64) were also significantly higher in patients with tinnitus (p = 0.018 and p = 0.008, respectively). In addition, significant positive correlations were found between T(p-e), T(p-e)/QTc ratio and disease duration (r = 0.792, p < 0.001; r = 0.500, p < 0.001, respectively).ConclusionAs a result, patients with tinnitus may have an increased risk of malignant ventricular arrhythmia.

Myocardial infarction in the absence of obstructive coronary artery disease - can the underlying causes be identified by cardiac magnetic resonance?

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease (MINOCA) is a clinical entity that occurs in up to 15% of all acute coronary syndromes (ACS). It is a "working diagnosis", as it is constituted by several etiologies. Purpose To identify the utility of CMR in determining the etiological diagnosis of MINOCA events, with potential impact in the therapeutic management of these patients. Methods Patients with MINOCA who were admitted to the Cardiology department at a tertiary center, between 2015 and 2020, were included. MINOCA was defined as an ACS with non-obstructive (&amp;lt;50%) coronary artery disease and no other clinically specific cause, in accordance with definition adopted in the 2020 ESC Guidelines for the management of ACS in patients presenting without persistent ST-segment elevation. Patients who did not had a coronary exam (either CT or invasive angiogram) or a CMR were excluded. All CMR exams were performed in a 3 Tesla equipment using a comprehensive protocol (cine, T2-weighted, and late gadolinium sequences). Clinical, electrocardiographic, echocardiographic and CMR data were collected. Results In a population of 29 patients, the mean age was 55 ± 17 years-old at the time of the cardiac event, 51.7% were male. Concerning to cardiovascular risk factors, 58.6% of patients had dyslipidaemia, 51.7% had hypertension, 13.7% were diabetic, 41.4% were smokers or previous smokers and 31.0% had obesity. Atrial fibrillation was present in 3.4% of patients. As for the EKG patterns, 41.4% of the patients had ventricular repolarization changes, 13.8% had a transitory ST elevation pattern, 6.9% had a complete left bundle branch block and 37.9% had a normal EKG; most of the ischemic EKG alterations were on the anterior wall (66.7%). The median high sensitivity I troponin levels were 1877.5 (IQR 225.3 – 5985.8) ng/L. The majority of patients (58.6%) had echocardiographic wall motion abnormalities; of those, the most common (41.1%) were on the left anterior descendent artery territory. CMR (performed at a median of 5 days from presentation) was able to identify the cause for the troponin rise in 58.6% of the cases; late gadolinium enhancement and oedema were present in 41.4% and 62.1% of patients, respectively. The mean left ventricle ejection fraction (EF) was 57.7 ± 8.5% and the mean right ventricle EF was 61.5 ± 6.1%. An ischemic pattern was present in 29.4% of the total population. In 17.6% of the patients findings were consistent with Takotsubo syndrome and in 29.4% with myocarditis. Conclusion CMR established the etiological cause in 58.6% of the cases, with potential implications in medical therapy. These findings highlight the importance of CMR in MINOCA diagnosis and the potential improvement in patient care with multi-modality imaging.