Average QT Research Articles

The Effectiveness of Ablation Therapy for Atrial Fibrillation: A Systematic Review.

It is expected that the prevalence of atrial fibrillation (AF), the most prevalent cardiac arrhythmia among people aged 65 to 85, would be mostly classified using the CHAS2DS2-VASc approach for anticoagulation therapy. A high number of people in the entire world will be living with AF by 2030. Long-term follow-up data are sparse, although radiofrequency catheter ablation (CA) for symptomatic AF patients has the potential to be a curative therapy. Although women are referred later and less often than men, the outcomes following ablation are comparable across both genders. Health-related quality of life suffers from AF, and patients often find themselves less active as a result of their condition. AF may have a wide variety of symptoms and signs from the clinic's point of view. Women are more likely to exhibit symptoms than men; one reason for this is that women have an average QT interval that is 10-20 milliseconds longer than men, which is more likely to exacerbate tachycardia symptoms. In search of medical databases for relevant medical literature, we looked at PubMed/Medline, the Cochrane Library, and Google Scholar. Ten publications were gathered after the papers were located, assessed, and qualifying criteria applied were used to select them. The finished articles were done to give an overview of the effectiveness of ablation therapy for AF. Some studies showed that there was no statistical significance between invasive and pharmacological treatments. Other research found no difference in the recurrence of atrial arrhythmia between pulmonary vein isolation (PVI) CA alone and PVI + enhancement magnetic resonance imaging (MRI)-guided fibrosis ablation in individuals with persistent AF. The oldest individuals in studies comparing CA to medical treatment for AF demonstrated no improvement in prognosis after CA. Also, complications from therapy and CA's efficacy in preventing future atrial arrhythmias were similarly low across all age groups. Based on the above, we concluded that more studies are required to establish the most effective approach to treating AFto apply it in daily practice and gain more knowledge about it.

Teaching medical students the QT interval and its autonomous regulation in a practical ECG course in physiology

Background: The QT interval is a well established marker for ventricular repolarization. As the QT interval is inversely regulated with the heart rate, several correction formula are established to calculate corrected QT intervals (QT c ). In practical courses of physiology, medical students learn the correct measurement of the QT interval and its autonomous regulation. For this, students record and analyse ECGs under resting conditions and during/following a workout. However, little is known about teaching QT/QT c skills in students. In particular, it is not established whether untrained medical students can determine the length of the QT interval in rest and following an exercise with sufficient accuracy to allow discussion of its physiological regulation. Methods: A full cohort of 3rd year medical students (n=380) participated in a practical ECG course. In each course (20 students), ECGs of volunteers were recorded in small groups (2-4 students) under resting conditions and immediately following standardised physical exercise (squats and push-ups). Students calculated HR, QT intervals and QT c intervals using Bazett’s exponential correction. Automatically calculated QT intervals were retrieved from the ECG devices. Following the course, QT intervals of the same ECG passages were measured by experienced physiology teachers and expert clinical electrophysiologists. To compare effects of established QT c correction formulas, QT c was calculated for all retrieved intervals using Bazett, Framingham, Fridericia and Hodges. Data were analysed on the level of individual experiments and as pooled data of student groups. Results: In 117 experiments, students reported resting HRs of ~70 bpm and corresponding QT intervals of ~360 ms. Following exercise, students found an average increase of the HR by ~75% and a decrease of the QT interval by ~25%. Using pooled data sets of each course, the overall efficacy of the Bazett formula could well be demonstrated. Students HR data were highly concordant with the data generated by the automated ECG routines, the experienced physiologists and the clinical electrophysiologists. While average QT and QT c intervals were also comparable between the groups, the variance was substantially higher in students data than in the other groups, especially in the exercise ECGs. In the HR ranges generated in the course, QT correction by Fridericia and Framingham was more efficient than by Bazett and Hodges. Conclusions: Untrained students can determine QT intervals from ECGs recorded under resting conditions and following a workout with sufficient accuracy to demonstrate the autonomous regulation of this important (bio)marker on the level of individual data sets. Due to the high individual variance of the QT c , however, we recommend QT c correction based on data pooled within each student group to discuss the relevance of the QT correction formulas. The study was financed by institutional budget. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparison Between QT and Corrected QT Interval Assessment by an Apple Watch With the AccurBeat Platform and by a 12‑Lead Electrocardiogram With Manual Annotation: Prospective Observational Study.

BackgroundAbnormal prolongation or shortening of the QT interval is associated with increased risk for ventricular arrhythmias and sudden cardiac death. For continuous monitoring, widespread use, and prevention of cardiac events, advanced wearable technologies are emerging as promising surrogates for conventional 12‑lead electrocardiogram (ECG) QT interval assessment. Previous studies have shown a good agreement between QT and corrected QT (QTc) intervals measured on a smartwatch ECG and a 12-lead ECG, but the clinical accuracy of computerized algorithms for QT and QTc interval measurement from smartwatch ECGs is unclear.ObjectiveThe prospective observational study compared the smartwatch-recorded QT and QTc assessed using AccurKardia’s AccurBeat platform with the conventional 12‑lead ECG annotated manually by a cardiologist.MethodsECGs were collected from healthy participants (without any known cardiovascular disease) aged >22 years. Two consecutive 30-second ECG readings followed by (within 15 minutes) a 10-second standard 12-lead ECG were recorded for each participant. Characteristics of the participants were compared by sex using a 2-sample t test and Wilcoxon rank sum test. Statistical comparisons of heart rate (HR), QT interval, and QTc interval between the platform and the 12-lead ECG, ECG lead I, and ECG lead II were done using the Wilcoxon sign rank test. Linear regression was used to predict QTc and QT intervals from the ECG based on the platform’s QTc/QT intervals with adjustment for age, sex, and difference in HR measurement. The Bland-Altman method was used to check agreement between various QT and QTc interval measurements.ResultsA total of 50 participants (32 female, mean age 46 years, SD 1 year) were included in the study. The result of the regression model using the platform measurements to predict the 12-lead ECG measurements indicated that, in univariate analysis, QT/QTc intervals from the platform significantly predicted QT/QTc intervals from the 12-lead ECG, ECG lead I, and ECG lead II, and this remained significant after adjustment for sex, age, and change in HR. The Bland-Altman plot results found that 96% of the average QTc interval measurements between the platform and QTc intervals from the 12-lead ECG were within the 95% confidence limit of the average difference between the two measurements, with a mean difference of –10.5 (95% limits of agreement –71.43, 50.43). A total of 94% of the average QT interval measurements between the platform and the 12-lead ECG were within the 95% CI of the average difference between the two measurements, with a mean difference of –6.3 (95% limits of agreement –54.54, 41.94).ConclusionsQT and QTc intervals obtained by a smartwatch coupled with the platform’s assessment were comparable to those from a 12-lead ECG. Accordingly, with further refinements, remote monitoring using this technology holds promise for the identification of QT interval prolongation.

Analysis of athlete QT intervals by age: Fridericia and Hodges heart rate corrections outperform Bazett for athlete ECG screening

BackgroundCardiac screening of elite athletes including a 12‑lead electrocardiogram (ECG) is recommended by numerous international bodies. Current athlete ECG interpretation guidelines recommend the Bazett method to correct the QT interval (QTc). ObjectiveThis study sought to investigate normative QTc changes by age using athlete screening ECGs and different QT correction methods in a population of elite cricketers. MethodsInitial cardiac screening ECGs from an existing database of elite Australian cricketers aged 14–35 years were examined. Average QT interval, QTcB (corrected QT–Bazett), QTcF (Fridericia), QTcH (Hodges), and heart rate (HR) were analyzed by age and sex. ResultsA total of 1310 athletes (66% male, 34% female) were included with mean age 19.1 years and mean heart rate 66.9 bpm (range 38-121 bpm). With increasing age, HR decreased and absolute QT increased. The pattern of QTc change with age differed depending on the method of correction: Bazett correction (QTcB) demonstrated a “dish-shaped” or broad U-shaped appearance; while Fridericia and Hodges corrections showed a linear increase in QTc from young to older age. The Bazett method had a stronger correlation of HR with QTc (R2 = 0.32) than either Fridericia (R2 = 0.0007) or Hodges (R2 = 0.009) methods. ConclusionsThe Bazett method is not the most accurate QT correction in athletes, especially during adolescence. In elite cricketers, QTcB revealed a drop in QTc from adolescence to early adulthood due to mis-correction of the QT interval. The Fridericia method has the smoothest correction of HR and least QT variation by age and may be preferred for athlete screening.

Effect and benefit of percutaneous coronary intervention in chronic total occlusion on ventricular repolarization: QT correction and dispersion.

ST segment, T wave changes, QT interval changes, and QTc dispersion are among the parameters used to diagnose ischemic heart disease. The increase in the QT dispersion can be caused by myocardial ischemia, among other heart diseases, whereas cardiac diseases such as coronary artery disease (CAD) can be diagnosed by observing an abnormally high QTc dispersion. This study aimed to evaluate the variations in the QTc dispersion (depolarization and repolarization) of surface electrocardiography as a result of percutaneous coronary intervention (PCI) in patients with chronic total occlusion. This study took place in the Iraqi Center for Heart Disease from October 2020 to February 2021. 110 patients who suffered from chronic occlusion of the coronary artery and underwent PCI revascularization were examined. Twelve-lead electrocardiograms were recorded at the time of admission (12 hours before intervention) and more than one hour after the intervention. The measured ECG parameters included corrected QT interval durations and corrected QT dispersion in both pre and post-PCI electrocardiograms, and their values were compared. The average corrected QT interval and QTC dispersion changed significantly before and after the percutaneous coronary intervention. Performing percutaneous coronary intervention on patients who suffer from coronary artery total occlusion shows a major reduction in the corrected QT dispersion.

Association of single nucleotide polymorphic variants of the <i>NOS1AP</i> gene with QT interval duration

Highlights. The association of single nucleotide polymorphic variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval was found in men of the Siberian population.Aim. To study the association of single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval.Methods. The study sample of men (1353 people) aged 25–69 years was formed from the DNA bank of participants in the international HAPIEE project and screening of young people 25–44 years old, residents of Novosibirsk. From each age subgroup (25–29, 30–34, …, 65–69 years old), about 10–15% of men with the shortest, average and longest QT interval were selected and the corresponding groups were formed. Genotyping of rs4657139 was carried out using PCR with RFLP (polymerase chain reaction followed by restriction fragment length polymorphism analysis). Genotyping rs12143842 – using RT-PCR (real-time polymerase chain reaction).Results. At the age of over 50 years, the CC genotype rs12143842 was detected in 66.1% of men in the group with a short and average QT interval and in 50.6% in the group with a long QT interval, while the TT genotype prevailed in the group with a long QT interval, 10, 8% of cases (odds ratio (OR) = 3.345, 95% confidence interval (CI) 1.149–9.739, p = 0.02). The homozygous TT genotype rs4657139 was more common in the long QT group, in 20.1% of cases, while the AA and AT genotypes predominated in the short, average QT groups (p = 0.041). A similar trend persists when separating by age in people over 50 years of age (p = 0.031) and when comparing genotype frequencies in the long and average QT groups in the model TT vs AA + AT & long QT vs short + average QT (p = 0.003).Conclusion. Single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene are associated with the duration of the QT interval in male residents of Novosibirsk.

Impact of Hydroxychloroquine Treatment of COVID-19 on Cardiac Conduction: The Beat Goes On

Objectives: Our study aimed to investigate the frequency of malignant cardiac arrhythmias in hospitalized patients receiving hydroxychloroquine alone and those receiving a combination of hydroxychloroquine with azithromycin, as well as the quantitative extent of QT prolongation within Tisdale Risk Score (TRS) categories. Background: There have been over 33 million cases of SARS-CoV-2 (COVID-19) resulting in over 600,000 deaths in the United States. As the current COVID-19 pandemic continues, numerous medications have been administered to attempt to treat patients afflicted by the disease. While hydroxychloroquine has been in use for decades for rheumatologic and infectious disease processes, it does have potential cardiotoxicity related to drug-induced QT prolongation. Drug-induced QT prolongation has an increased risk of arrhythmogenicity, potentially progressing into torsades de pointes (TdP) and increased patient mortality. The relationship between QT prolongation and TdP is complex and inexact, but there remains optimism regarding the use of these medications in the treatment of COVID-19 despite limited data on their true efficacy. Methods: We retrospectively identified 75 patients who were admitted with COVID-19 and underwent treatment with hydroxychloroquine for 5 days. The hydroxychloroquine protocol was defined as an initial dose of 400 mg BID for the first day, followed by 400 mg daily for the next 4 days. Baseline demographics, medications, medical histories, lab values, ECG QT intervals, and Tisdale Risk Categories were collected for all patients. Results: Seventy-four (98.7%) patients completed the full course of hydroxychloroquine. There were 41 males (54.7%) and 34 females (45.3%). Average length of stay was 8.9 days (95% CI: 7.5, 10.2). One patient who could not complete the course due to inability to swallow medication tablets. There were no reports of new arrythmias or incidence of torsades de pointes during the study. Seventy-two patients (96%) were taking at least 2 QT prolonging medications. The average corrected QT intervals were as follows: day 1 of admission was 421.62 milliseconds (n = 66, 95% CI: 412.19, 431.05), day 2 was 431.50 ms (n = 30, 95% CI: 416.34, 446.66), day 3 was 433.48 ms (n = 23, 95% CI: 413.34, 453.61), day 4 was 427.59 ms (n = 17, 95% CI: 400.83, 454.35), and day 5 was 444.28 ms (n = 18, 95% CI: 428.43, 460.12). The corrected QT interval prolonged by 22.66 ms from day 1 to day 5 (p = 0.03) in the overall population. Conclusion: There were no patients who experienced arrhythmogenicity or Torsades de Pointes despite a statistically significant increase in QTc intervals after patients received the 5-day course of hydroxychloroquine for treatment of COVID-19.

QT Interval Dynamics and Cardiovascular Outcomes: A Cohort Study in an Integrated Health Care Delivery System.

BackgroundLong QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within‐person QT change over time in relation to risk of incident CVD and all‐cause mortality in a real‐world setting.Methods and ResultsA cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non‐White) with 3 or more ECGs (baseline in 2005–2009; mean±SD follow‐up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all‐cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all‐cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all‐cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07).ConclusionsOur results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long‐term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.

Repolarization dispersion in patients with systemic sclerosis.

Systemic sclerosis (SSc) is associated with increased cardiac morbidity and mortality. Whether some electrocardiographic markers of arrhythmias predispose to early cardiogenic death in SSc remains controversial. This study evaluated the occurrence of previously reported as well as unstudied markers of repolarization in patients with SSc and assessed their prognostic implications. A total of 21 patients with SSc and 31 unaffected controls were included in this prospective study. Electrocardiograms were conducted under strict standards. Repolarization and dispersion parameters and markers of late ventricular potentials were determined using designated computer software. Results of multiple beats were averaged. There were no significant differences between the SSc and control groups in average QT intervals, average corrected QT intervals, average QT interval dispersion (QTd), average QT corrected dispersion (QTcd), and QT dispersion ratio. However, average QT apex dispersion, average JT dispersion, average JT corrected dispersion, and Tpeak-Tend corrected were significantly higher in patients with SSc than in controls. Late ventricular potentials were not found in patients with SSc or in controls. Increased QTd and QTcd were recorded in 1 patient who experienced ventricular arrhythmia before inclusion in the study. None of the remaining patients with SSc or the controls developed arrhythmia during the 9-year follow-up. Abnormal repolarization parameters may be observed in patients with SSc. However, their prognostic significance with regard to increased risk for repolarization-associated ventricular arrhythmias and increased cardiac death could not be determined in this study. Our findings endorse additional studies on this matter.

The relationship between QT interval and pain severity in trauma patients in the emergency department

Aim: Cardiac depolarization occurs in patients experiencing pain from acute traumas, and changes in QT interval could indicate the state of ventricular depolarization. Thus, we aimed to determine the relationship between pain severity and QT interval in patients experiencing acute trauma. Material and Method: Seventy patients, who were conscutively- admitted to the Emergency Department due to moderate or severe trauma (study group), and sixty healthy individuals (control group) were included in this study. The QT interval was calculated for each group before and after analgesia and visual analog scale pain levels were recorded. Statistical analyses were performed using SPSS for Windows software (ver. 21.0; SPSS Inc., Chicago, IL, USA). Data are presented as medians±interquartile range (IQR). Statistical significance was determined using Mann-Whitney U, Wilcoxon, and chi-square tests, with a p-value <0.05 considered significant. Results: The mean age of patients with trauma and control patients was 31.50±25 years and 35.00±20 years, respectively. Among trauma patients, QT, RR and corrected QT (QTc) intervals were significantly different before and after analgesia (P<0.001). Similarly, the average pre-analgesia QT, RR and QTc values also differed between pre- and post-analgesia trauma patients (p=0.007, p<0.001, and p<0.001, respectively). However, no differences in QT values were observed before and after analgesia between patients experiencing moderate versus severe pain (p>0.05). Conclusion: In trauma patients, acute pain prolonged the QT interval, which reverted to normal following the administration of nonsteroidal anti-inflammatory drugs. However, additional comparative studies on this topic are required.

QT Dispersion and Drug-Induced Torsade de Pointes.

BackgroundAmiodarone causes less drug-induced torsade de pointes (TdP) compared to other class III antiarrhythmics. Two theories proposed for this finding include that amiodarone has less repolarization heterogeneity, and/or decreases early after depolarization (EADs). Corrected QT (QTc) dispersion as measured on a surface electrocardiogram (ECG) represents spatial heterogeneity of ventricular repolarization.ObjectiveThe purpose of this study was to analyze the difference in QT dispersion between amiodarone and other class III antiarrhythmics and to determine the etiology of TdP.MethodsThis was a retrospective, observational study at Montefiore Medical Center between January 2005 and January 2015. Inclusion criteria were adults >18 years on amiodarone, dofetilide, or sotalol with prolonged QT interval on 12-lead ECG. ECGs were reviewed by three blinded observers. QTc was calculated using the Bazett and Framingham formulas. QTc dispersion was calculated by subtracting the shortest from the longest QTc. Analysis of variance (ANOVA) was applied for comparison between antiarrhythmic groups with Bonferroni correction for multiple comparisons.ResultsA total of 447 ECGs were reviewed and 77 ECGs met inclusion criteria. The average QT dispersion for amiodarone, dofetilide, and sotalol was 0.050, 0.037, and 0.034, respectively (p=0.006) and the average QTc dispersion by Bazett was 0.053, 0.038, and 0.037 (p=0.008) and by Framingham was 0.049, 0.036, and 0.035 (p=0.009), respectively.ConclusionOur results show that given the increase in QT dispersion seen with amiodarone, heterogeneous ventricular repolarization as measured by QTc dispersion likely does not account for the lower incidence of drug-induced TdP seen with amiodarone. The ability of amiodarone to decrease EADs via sodium-channel blockade is more likely the explanation for its lower incidence of drug-induced TdP.

Safely Administering Potential QTc Prolonging Therapy Across a Large Health Care System in the COVID-19 Era.

The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic. Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy. The incidence of torsade de pointes remains unknown. Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment. Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study. A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest. The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin. Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5. There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced. The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy.

P1502 A clinical case of mitral annulus disjunction syndrome revealed by cardiac MRI

Abstract A 39year old female patient with a family history of probable sudden cardiac death/long QT syndrome (sister died aged 36) was referred to our Arrhythmia/inherited cardiac conditions clinic. Patient was fit and well. She described occasional postural presyncope and some chest pain with stress. Not on any medication that could prolong QT. On examination she appeared well with normal heart sounds and no clinical signs of heart failure. Her ECG in clinic confirmed sinus rhythm with normal QTc at 418msec. There were U waves which may reflect late repolarisation of His Purkinje system. Diagnostic techniques and findings A 24-hour ECG tape to look at the average QT interval, an exercise tolerance test to look for appropriate shortening of QT interval with exercise and an echocardiogram to exclude significant structural abnormality were requested. The 24-hour ECG tape confirmed underlying sinus rhythm with multi-focal aberrant beats <1% of total. One symptom demonstrated short run of ventricular bigeminy. During the exercise tolerance test, QT interval was not obviously prolonged. There were frequent bifocal ventricular ectopic beats in recovery. The echocardiogram showed minor abnormality with mild left ventricular dilatation, otherwise normal findings. Patient referred for cardiac MRI In order to rule out any cardiomyopathy. Cardiac MRI did not show any prolapse on the 3 chamber cine. In addition, the inferior and inferolateral annulus showed thinning passing into the LV, which is a feature of some patients with mitral annulus disjunction syndrome. We went through the echocardiogram and in one single frame images are suspicious of focal P2 prolapse. Learning points: Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral valve leaflet hinge point. It has been associated with mitral valve prolapse and sudden cardiac death. MAD is usually revealed with echocardiogram. In this case report we showed that CMR revealed a MAD previously missed by echo. Abstract P1502 Figure.

Magnetocardiographic identification of prolonged fetal corrected QT interval in women receiving treatment for opioid use disorder.

Pregnant women undergoing treatment for opioid use disorder (OUD) may be exposed to multiple QT prolonging agents. We used magnetocardiography to measure fetal QT intervals in mothers with OUD on buprenorphine therapy. Fetal and maternal magnetocardiography was performed in pregnant women receiving buprenorphine-assisted treatment (Disorder group); these were matched by gestational age to pregnant women who were opiate naïve (Reference group). Corrected QT intervals were determined using Bazett's formula and compared between groups. A total of eight women in the Disorder group matched to eight in the Reference group. Seven of the mothers (88%) in the Disorder group were smokers; there were no smokers in the Reference group. The average fetal corrected QT was significantly longer (P = 0.022) in the Disorder group than that in the Reference group (505 milliseconds [ms] ± 68.6 [standard deviation] vs 383 ms ± 70.3 [standard deviation]). Novel data from this small sample demonstrate prolongation of fetal corrected QT in women with OUD participating in buprenorphine assisted therapy. Additional investigation from a larger sample is needed to clarify if fetal buprenorphine and/or tobacco exposure is associated with changes in fetal QT which would warrant further prenatal and postnatal testing.

Sleep Arousal and Sudden Changes in Cardiac QT Interval.

Sleep arousal is generally defined as an abrupt shift in EEG frequency with a duration of 3-16 seconds. Arousal from sleep expected to cause sudden changes in the cardiovascular system that can manifest as cardiac responses. In this paper, our objective was to investigate how cardiac characteristics change due to arousal. We focused on the QT interval fluctuations in ECG during the occurrence of arousals. We analysed 7373 sleep arousals collected from 50 males that were older than 65 years. We analysed the ECG signal 5 seconds prior to and 10 seconds after each arousal onset (Pre and Post-Onset). Q and T waves were detected for all Pre and Post-Onset windows to estimate their time intervals. To find out whether the QT interval, a marker of ventricular activation, is modulated by arousal onset, we have applied graphical and statistical analysis. Our observations indicate that in 47 out of 50 subjects (94%), the average QT interval of all arousal significantly shortened at arousal onset. We observed similar outcomes for different types of arousals, indicating that the shortening in average QT interval is independent of the type of arousal. We also studied the relative QT interval change during arousal. The distribution of relative QT interval changes demonstrates that around 60% of arousals increase or decrease QT interval by a maximum of 20%. The probability of QT time interval shortening was twice that of QT interval lengthening.

Video-Assisted Thoracoscopic Left Cardiac Sympathetic Denervation in Chinese Patients with Long QT Syndrome.

Long QT syndrome is a rare but potentially lethal cardiac channelopathy. The primary aim of the study was to investigate the long-term effects of video-assisted thoracoscopic (VATS) left cardiac sympathetic denervation (LCSD) in Chinese patients with long QT syndrome.VATS-LCSD was performed in eight Chinese patients with LQTS. Twelve-lead ECGs and 24-hour Holter monitoring ECGs were recorded before and after surgery. The medical charts were reviewed to obtain patient data, and the patients who had been lost to follow-up were contacted through telephone.The average QTc was shortened from 534 ± 52.7 to 503 ± 43.7 ms (P = 0.030) 24 hours post-surgery and down to 486 ± 34.8 ms (P = 0.021) 1 week post-surgery, with the heart rate unchanged. The average QT dispersion was reduced from 67 ± 17.5 to 21 ± 3.9 ms (P < 0.001) 24 hours post-surgery and remained shortened 1 week later (30 ± 8.1 ms, P < 0.001). Moreover, the 24-hour ECG showed that the QTc was shortened from 552 ± 95.9 to 497 ± 19.7 ms at the minimum heart rate (P = 0.008), and was decreased from 594 ± 144 to 495 ± 74.1 ms at the maximum heart rate (P= 0.04), while the minimum and maximum heart rates were comparable before and after surgery. No death was observed during the follow-up period and the clinical symptoms improved in all patients. The annual event rate decreased from 4 ± 3.50 to 0.63 ± 1.37 events/year (P = 0.034) after surgery.These findings indicate that LCSD shortens the QTc, with the heart rate remaining unchanged. QTd might be a useful parameter for evaluating the efficacy of VATS-LCSD. LCSD could improve patients' life quality by reducing cardiac events.

QT instability, an indicator of augmented arrhythmogenesis, increases with the progression of myxomatous mitral valve disease in dogs

ObjectivesTo investigate QT instability in dogs with myxomatous mitral valve disease (MMVD) and to determine if this is associated with arrhythmogenesis. AnimalsOne hundred sixty-seven MMVD dogs that met the study criteria were included. MethodsEchocardiographic and electrocardiographic data were gathered. Fifty consecutive QT intervals were recorded for each dog. Both heart rate–corrected and uncorrected QT intervals were used to calculate average QT (QTa), QT variance (QTv), total instability (TI), short-term instability (STI), and long-term instability (LTI). Sensitivity and specificity of QTa, QTv, TI, STI, and LTI in identifying arrhythmias and cardiac remodeling were calculated. Patient follow-ups were obtained for analyses of disease progression and survival. ResultsAn increase related to progression was documented for all the studied indices. QTa and STI best identified dilated hearts and arrhythmias, respectively. Dogs with QTa >272 ms and STI >8 ms were 15% more likely to develop ventricular arrhythmias (likelihood ratios of 2.31 [P = 0.0008] and 2.09 [P = 0.0049], respectively). A QTa >258 ms discriminated American College of Veterinary Internal Medicine stage B1 from stages B2/C disease with a sensitivity of 63% and specificity of 61%. Dogs in American College of Veterinary Internal Medicine stage C of MMVD have higher STI and 3.34 times increased risk of developing arrhythmias when values more than 8 ms are reached. All indices except LTI and QTv showed prognostic value, with increases relating to all-cause mortality. ConclusionAnalyses of QT intervals demonstrated changes in STI, LTI, and TI. Increased QT prolongation and instability are significantly related to mortality and may be useful in determining prognosis of MMVD patients.

Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G.

Calmodulin (CaM) is encoded by 3 genes, CALM1, CALM2, and CALM3, all of which harbor pathogenic variants linked to long QT syndrome (LQTS) with early and severe expressivity. These LQTS-causative variants reduce CaM affinity to Ca(2+) and alter the properties of the cardiac L-type calcium channel (CaV1.2). CaM also modulates NaV1.5 and the ryanodine receptor, RyR2. All these interactions may play a role in disease pathogenesis. Here, we determine the spectrum and prevalence of pathogenic CaM variants in a cohort of genetically elusive LQTS, and functionally characterize the novel variants. Thirty-eight genetically elusive LQTS cases underwent whole-exome sequencing to identify CaM variants. Nonsynonymous CaM variants were over-represented significantly in this heretofore LQTS cohort (13.2%) compared with exome aggregation consortium (0.04%; P<0.0001). When the clinical sequelae of these 5 CaM-positive cases were compared with the 33 CaM-negative cases, CaM-positive cases had a more severe phenotype with an average age of onset of 10 months, an average corrected QT interval of 676 ms, and a high prevalence of cardiac arrest. Functional characterization of 1 novel variant, E141G-CaM, revealed an 11-fold reduction in Ca(2+)-binding affinity and a functionally dominant loss of inactivation in CaV1.2, mild accentuation in NaV1.5 late current, but no effect on intracellular RyR2-mediated calcium release. Overall, 13% of our genetically elusive LQTS cohort harbored nonsynonymous variants in CaM. Genetic testing of CALM1-3 should be pursued for individuals with LQTS, especially those with early childhood cardiac arrest, extreme QT prolongation, and a negative family history.

Abstract 18556: Renal Sympathetic Denervation Modulates Cardiac Repolarization in a Post Myocardial Infarction Pig Model

Introduction: Changes in cardiac repolarization parameters such as QT interval and QT dispersion have been implicated in cardiac arrhythmogenesis following acute myocardial infarction (AMI). These parameters are susceptible to sympathetic modulation. We therefore hypothesized that renal sympathetic denervation (RDN) may produce potential anti-arrhythmic actions through its effects on cardiac repolarization. Methods: Fifteen pigs randomized to AMI &amp; RDN (6 pigs), AMI &amp; sham RDN (6 pigs) and sham MI &amp; sham RDN (3 pigs) underwent percutaneous occlusion of the mid to distal LAD to achieve AMI. 2 weeks after infarction, the St. Jude EnligHTN® basket catheter was used to perform RDN bilaterally. Cardiac repolarization parameters were measured at 3 time points over the course of the 3 week study: baseline (immediately before MI), midpoint (2 weeks post MI; at time of RDN) and end (1 week post RDN). ECG data were acquired from limb leads. Results: In a ten beat span, the range in the durations of the QT interval was seen to increase from 18+/-7ms to 19+/-11ms in the real AMI &amp; sham RDN group while in the real AMI &amp; real RDN group it decreased from 17+/-5ms to 14+/-5ms (p=0.11). The mean QT interval which increased by 25% in the real AMI &amp; sham RDN group saw only an 11% increase in the real AMI &amp; real RDN group (p=0.048). The standard deviation of the average QT intervals post AMI, which quantifies the reduction in global dispersion of repolarization, saw a 41% decrease with RDN compared to an 8% decrease with sham RDN. The temporal dispersion of repolarization was also diminished by RDN. The dispersion of T wave peak to T wave end durations which increased in the real AMI &amp; sham RDN group (from 15+/-6ms to 22+/-10ms), was decreased in the real AMI &amp; real RDN group (from 19+/-7ms to 16+/-6ms) (p=0.05). T wave alternans values displayed no significant response to RDN (p=0.977). Conclusions: Adverse changes in cardiac repolarization parameters were attenuated via renal denervation in this post infarct pig model. These effects may mitigate post infarct arrhythmogenesis but require further study to evaluate the influence of local, reflex and circulating mediators.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.