Median QTc Research Articles

Abstract 4147633: Structural and Electrophysiological Cardiac Changes in Children with Osteogenesis Imperfecta (OI)

Introduction: Osteogenesis imperfecta (OI) is an inherited type 1 collagen disorder leading to bone fragility and increased fractures. Cardiovascular disease is the leading cause of death of adults with OI, but studies on cardiac changes from this collagen defect in children are sparse. We aim to fill this gap by assessing changes in EKG and echocardiogram (ECHO) variables in children with OI. Hypothesis: Children with OI will exhibit arrhythmogenic EKG changes and/or ECHO abnormalities which will precede changes that are documented in adults. Methods: 53 children with OI receiving care at Children’s Mercy-Kansas City were identified via ICD-10 codes. 64 with Duchenne Muscular Dystrophy (DMD, expected cardiac abnormalities) and 55 with non-accidental trauma (NAT, no expected cardiac abnormalities) served as controls. We specifically compared the most recent EKG and ECHO metrics extracted from medical charts by Kruskal-Wallis testing. Results: EKG: Children with OI differed from both NAT and DMD. OI had shorter median PR intervals (p<0.001) plus longer median QRS (p<0.001) and QTc intervals (p=0.002) than NAT. DMD had the shortest PR and longest QRS and QTc (see Table). Echo: The three groups showed no difference in systolic/diastolic BP or LV thickness. However, OI differed from NAT and/or DMD in other metrics. OI had higher end diastolic volume (p<0.001), end systolic volume (p<0.001) and stroke volume (p<0.05) than NAT, but lower values than the DMD group. Similarly, OI children had higher LV mass and LV internal diastolic and systolic diameters than NAT, but lower than DMD (p<0.001). OI LVOT diameter and Aortic root diameter were lower than NAT, but not as low as DMD (p<0.05 and p<0.001, respectively). Conclusion: Children with OI exhibit EKG and ECHO abnormalities that are similar to but less severe than for DMD, a group in which cardiovascular abnormalities are well documented. These abnormalities may be predictive of arrythmia/sudden cardiac death and/or functional decline in heart function. Our data suggest that OI children could benefit from ongoing routine cardiology studies along with orthopedic/metabolic management. Future studies would assess effects of age and OI treatments on cardiac abnormalities.

Significance of J wave with inverted ST-T polarity induced by ill-timed atrial premature beats and its association with Torsade de Pointes in patients with acute acquired long QT syndrome

Abstract Background When ventricular cardiomyocytes become depolarized during their relative refractory period (RRP), the amplitude of the action potential (AP) becomes lower than that of preceding AP, since some sodium channels are in their refractory state. If the membrane voltage does not reach a level high enough to activate voltage-dependent calcium channels, the AP duration becomes markedly shortened due to loss of AP dome. In patients with long QT syndrome (LQTS), intrinsic differences in AP duration and/or AP restitution kinetics exist between ventricular endocardium and epicardium. Thus, we hypothesized that atrial premature beats (APBs) can capture the RRP and amplify a transmural voltage gradient that manifests as a J wave with inverted ST-T polarity (APB-induced J wave). Purpose To investigate the prevalence of APB-induced J wave and examine the contribution to the development of Torsade de Pointes (TdP) in patients with acute acquired LQTS. Methods A total of 34 consecutive patients with acute acquired LQTS (14 men; median age, 69 years; median QTc, 645.5 ms) and documented TdP were enrolled. APBs were observed before the onset of TdP in 18 (52.9%) patients. The 34 patients were divided into 2 groups based on the presence or absence of APB-induced J wave with inverted ST-T polarity: APB-J wave group (n=8) and non-APB-J wave group (n=26). Results APB-J wave group constituted 23.5% (8/34) of the studied patients. There were no significant differences in clinical characteristics (sex, age and QTc) between the 2 groups. Macroscopic T-wave alternans was more frequently observed before TdP onset in APB-J wave group than non-APB-J wave group (75% vs 15.4%, p=0.003). The ill-timed APBs with J wave directly initiated TdP in all patients in APB-J wave group. APB-J wave group experienced TdP even after initiating conventional therapy more frequently than non-APB-J wave group (3.5 vs 1 event, p=0.04). Conclusions APB-induced J wave is observed in approximately one-fourth of acute acquired LQTS patients with TdP and is associated with an increased risk of TdP. Our observations suggest that APBs can amplify the transmural dispersion of repolarization manifested as a J wave.Figure1Figure2

Dynamic QTc interval changes observed in real-world patients with implanted insertable cardiac monitors taking class III antiarrhythmic drugs

Abstract Background QT prolongation can lead to sustained ventricular arrhythmias . Class III Antiarrhythmic drugs (AAD) are known to cause QT prolongation. Insertable cardiac monitors (ICM) have the capability to continuously monitor and detect dynamic changes in QT. Purpose To investigate the characteristics of QTc interval changes before and after antiarrhythmic drug loading in real-world ICM patients administered with Sotalol, Amiodarone, and Dofetilide in hospital. Methods The QT detection algorithm detects the T-waves and determines the QTc intervals for every beat, thus providing continuous long-term QTc trends from ICM ECG. Real-world patients from de-identified Electronic Health Record (EHR) database linked with ICM device data warehouse with implanted ICM being administered sotalol, amiodarone or dofetilide AAD for the first time in the hospital were analyzed. The patients were broken down into groups based on the AAD taken. Patients not taking AAD were selected as control. QTc intervals 7-days pre and post administered AAD are reported, and a random 14-day period was used for control patients. The paired difference in median QTc 7 days pre and post administered AAD were analyzed using the Wilcoxon signed rank test. The Wilcoxon rank-sum test was used to analyze QTc between the different groups. Results A total of 487 patients with ICM were included in this analysis: 56 sotalol patients (avg. age: 67±10 years, 50% male), 100 amiodarone patients (avg. age: 72±10 years, 50% male), 52 dofetilide patients (avg. age: 66±12 years, 50% male), and 248 control patients (avg. age: 70±13 years, 50% male). Sotalol, amiodarone, and dofetilide patients showed significant increase in QTc 1-7 days post AAD compared to 1-7 days pre AAD (figure 1). For sotalol (post AAD median[IQR] = 426.5[408.8,446.6] msec, pre AAD median[IQR] = 415.9[391,437.3] msec, p=0.004); Dofetilide (post median[IQR] = 432.4[413,458.7] msec; pre median[IQR] = 409.3[397.5,435.2] msec, p<0.001); Amiodarone (post median[IQR] = 426.3[400.9,449] msec, pre median[IQR] = 415.5[397.5,435.2] msec, p = 0.037). The QTc 1-7 days pre AAD compared to 1-7 days post AAD for control patients was insignificant p>0.05. The median change in QTc 1-7 days post AAD from 1-7 days pre AAD was 13.0, 7.5, 21.25 and -1.0 msec for sotalol, amiodarone, dofetilide, and control patients respectively (figure 2). Dofetilide patients had a significantly higher change in QTc compared to the amiodarone patients, p=0.018. QTc for all three AAD groups when compared to control group post AAD were significantly higher, p<0.001. QTc was also higher pre AAD compared to control, p=0.003, p<0.001, p=0.009 for sotalol, amiodarone, and dofetilide respectively. Conclusions There is a significant increase in QTc detected by ICM in patients receiving index drug loading of Sotalol, amiodarone and dofetilide. QTc monitoring via ICM can detect these dynamic changes in QTc allowing for early intervention.Figure 1Figure 2

Feasibility and accuracy of mobile QT interval monitoring strategies in bedaquiline-enhanced prophylactic leprosy treatment.

Some anti-mycobacterial drugs are known to cause QT interval prolongation, potentially leading to life-threatening ventricular arrhythmia. However, the highest leprosy and tuberculosis burden occurs in settings where electrocardiographic monitoring is challenging. The feasibility and accuracy of alternative strategies, such as the use of automated measurements or a mobile electrocardiogram (mECG) device, have not been evaluated in this context. As part of the phase II randomized controlled BE-PEOPLE trial evaluating the safety of bedaquiline-enhanced post-exposure prophylaxis (bedaquiline and rifampicin, BE-PEP, versus rifampicin, SDR-PEP) for leprosy, all participants had corrected QT intervals (QTc) measured at baseline and on the day after receiving post-exposure prophylaxis. The accuracy of mECG measurements as well as automated 12L-ECG measurements was evaluated. In total, 635 mECGs from 323 participants were recorded, of which 616 (97%) were of sufficient quality for QTc measurement. Mean manually read QTc on 12L-ECG and mECG were 394 ± 19 and 385 ± 18 ms, respectively (p < 0.001), with a strong correlation (r = 0.793). The mean absolute QTc difference between both modalities was 11 ± 10 ms. Mean manual and automated 12L-ECG QTc were 394 ± 19 and 409 ± 19 ms, respectively (n = 636; p < 0.001), corresponding to moderate agreement (r = 0.655). The use of a mECG device for QT interval monitoring was feasible and yielded a median absolute QTc error of 8 ms. Automated QTc measurements were less accurate, yielding longer QTc intervals.

Osimertinib related cardiotoxicity in patients with non-small cell lung cancer.

e20011 Background: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small cell lung cancer (NSCLC). Limited data exists for a comprehensive cardiotoxicity profile analysis for osimertinib in NSCLC patients. Methods: Data was retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System between 7/2016 and 1/2024. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated. Corrected QT interval was calculated using the Fredericia formula. QT prolongation was defined as a QTc &gt;500 milliseconds (ms). Results: A total of 116 participants with NSCLC on osimertinib were included in the analysis with median age of 52.2 years, 69.8% female, and mean 1.52 years of follow-up. The study population was 93.1% of white race, and significant comorbidities within the overall population included hypertension (70.7%), hyperlipidemia (53.4%), tobacco use (38.8%), coronary artery disease (18.1%) and diabetes mellitus (15.5%) (Table). Out of 85 patients with no specified prior cardiac abnormalities, 29.4% developed new onset cardiac abnormalities (Table). The median QTc increased from 429 ms to 444 ms after starting osimertinib, and 8.8% of patients had QTc &gt;500 ms. Conclusions: Osimertinib is used in NSCLC and appears to be associated with an increase in cardiac abnormalities. A direct causal relationship between osimertinib use and cardiotoxicity has not yet been established. Given the strong association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram and echocardiographic abnormalities. [Table: see text]

Evaluation of the Relationship Between Microalbuminuria/Creatinine Ratio and QTc Dispersion in Type 2 Diabetes Mellitus

Objective: The assessment of QTc dispersion (QTd) is of importance in determining the risk of ventricular arrhythmias and cardiac autonomic neuropathy (CAN) in patients with diabetic nephropathy (DN). Our study explored the relationship between the microalbumin/creatinine (MA/crea) ratio and QT(cd) in the context of CAN development in DN. Material and Methods: We selected fifty individuals with a spot urine MA/crea ratio of less than 30 as the control group and fifty individuals with an MA/crea ratio between 30 and 300 as the patient group. QT intervals were calculated using the Bazett formula, taking into account the heart rate. Results: In contrast to the control group, the patient group exhibited a considerably higher median QTc min value (380.63 msn, 361.44–397.30, p: 0.042) and a statistically significant increase in the median QTc max value (439.98 msn, 420.17–460.22, p=0.005). Furthermore, the median MA/crea value (82, 60–300, p&lt;0.0001) was found to be highly significant. However, the median QT(cd) value (61.25 msn, 49.91–81.70, p=0.066) was only marginally significant, with no statistically significant difference between the two groups. It is worth noting that both groups showed a significant difference in terms of QTd (p&lt;0.001). In the control group, where DN had not yet developed, the QT(cd) value could be detected before an increase in the MA/crea value. Conclusion: The findings that both the control group and the patient group exhibited elevated QTcd values suggest that this parameter may be a viable predictor of cardiovascular risk. Furthermore, it is conceivable that QTcd could serve as an early warning sign for cardiovascular risk in diabetic patients who have not yet reached the stage of microalbuminuria.

Continuous QT interval monitoring using insertable cardiac monitors during antiarrhythmic loading hospitalization: Results from the "LINQ QT" Study

Abstract Background QT interval prolongation is associated with the development of potentially lethal cardiac arrhythmias. An implantable cardiac monitor (ICM) capable of longitudinal QT monitoring may allow for mobile assessment of dynamic changes in QT and assist in predicting long term cardiotoxicity. Objective Determine feasibility of continuous QTc interval monitoring in patients with ICM hospitalized for antiarrhythmic drug loading. Methods The previously described QT detection algorithm for an ICM determines the QT interval for every beat thus providing continuous long-term QT trends. QT intervals detected from continuously collected ICM ECG data from patients enrolled in a prospective clinical study from three sites was analyzed with the primary objective of studying the long-term QT interval trends in patients undergoing antiarrhythmic drug loading in an inpatient setting. The ICM ECG was processed through the QT detection algorithm which calculates the QTc interval for every beat to generate continuous long term QTc trends. Metrics including mean and median QTc, minimum and maximum QTc, and magnitude of QTc change were studied during the hospitalization period. Continuous QTc interval trend is presented from a patient displaying increase in QTc interval following antiarrhythmic drug loading during the hospitalization period. Results 5 out of 17 patients enrolled (avg. age 71±7.3 years, 40% females) in the QT clinical study had continuous telemetered ICM ECG data available during the index antiarrhythmic loading hospitalization period. All patients were loaded with Sotalol during the hospitalization. All 5 patients had hypertension and atrial fibrillation (AF). 3 patients (60%) had a history of myocardial infarction (MI), congestive heart failure (CHF), and coronary artery disease (CAD) while 1 patient (20%) had diabetes. The magnitude of change in QTc over the hospitalization period was 139±42 msec with over 100 msec QTc change noticed in 4 of 5 patients (80%) (figure 1). Figure 2 shows continuous QTc interval trend observed from a patient (Male; Age:75; history of AF, hypertension, CHF, stroke) from this study showing a continuous increase in QTc interval. Overall, there was over 150 msec change in QTc observed for this patient during the hospitalization period. Premature ventricular complexes (PVCs) in a pattern of bigeminy were observed from ICM ECG for a 3-hr period from 12 pm-3 pm following the second antiarrhythmic dose which coupled with QT prolongation could indicate early signs of cardiotoxicity (figure 2). The five static 12-lead ECG measurements taken for this patient during the hospitalization period is also reported with the difference between these 12-lead QTc measurements and algorithm measured QTc being 22±8 msec. Conclusion ICM QT monitoring performed utilizing a QT interval detection algorithm can provide longitudinal and long-term dynamic QT trends in patients implanted with ICM.

Long-term QT interval analysis for real world patients with Insertable cardiac monitors taking antiarrhythmic drugs

Abstract Background The QT interval serves as a surrogate biomarker for ventricular repolarization. Variance in QT intervals can clinically lead to pro-arrhythmia and sudden cardiac death. An insertable cardiac monitor (ICM) device capable of continuously monitoring the QT interval over a long period can provide diagnostic value for evaluating physiologic or drug induced variations in QT interval. Objective To analyze feasibility of continuous QTc interval monitoring in patients with ICM and evaluate the QTc interval changes in patients taking antiarrhythmic drugs. Methods Patients QT intervals detected from daily ICM ECG data from real-world patients taking antiarrhythmic drugs such as sotalol, amiodarone and dofetilide during hospitalization while implanted with ICM were analyzed from the de-identified Electronic Health Record (EHR) database linked with ICM device data warehouse. The ICM ECG was processed through the previously defined QT detection algorithm which calculates the QTc interval for every beat to generate continuous long term QTc trends. A patient contributed to the prescription group if they were prescribed antiarrhythmics drugs prior to hospitalization in the EHR database otherwise they contributed to the non-prescription group. Patients from the prescription group who were administered antiarrhythmic drugs via injection or IV during hospitalization were removed from the analysis. A 30-day median QTc interval from 30-60 days prior to hospitalization was used as baseline. Wilcoxon signed-rank test was used to compare the paired difference from days 1-5, 1-10, 30-60, and 60-90 after hospitalization to their respective baseline. Results 441 patients (avg. age: 70±11, 50.5% female) were included with 220 prescription and 221 non-prescription. The baseline QTc intervals were 414 and 417.3 msec for non-prescription and prescription groups, respectively. There was a significant increase in QTc on days 1-5, 1-10, 30-60, and 60-90 after hospital admission compared to the baseline (all p &amp;lt; 0.001) for the non-prescription group. The prescription group showed increase in QTc only on days 30-60 after hospitalization when compared to baseline (p&amp;lt;0.05). A larger QTc increase was observed in non-prescription receiving anti-arrhythmic loading on days 1-5 after hospitalization compared to patients on prescription prior to hospitalization (P&amp;lt;0.05). Conclusion Utilizing a QT interval detection algorithm from an ICM can provide long term QT trends for patients with an ICM. Continuous monitoring of QT can help to detect sudden changes in QT due to antiarrhythmic drugs which may lead to increased risk of arrhythmias or cardiac arrest.

#2814 Characterization of cardiological manifestations in patients with sodium-wasting tubulopathies

Abstract Background and Aims Bartter (BS) and Gitelman (GS) syndromes are rare tubulopathies caused by mutations affecting renal NaCl transporters, resulting in similar symptoms like muscle weakness, cramps, and electrolyte imbalances, with GS also presenting with hypomagnesemia. Treatment focuses on electrolyte and fluid balance, using supplements and drugs to inhibit prostaglandin production and RAAS activation. Electrolyte deficits in these conditions can extend the QT interval and increase the risk of potentially fatal cardiac arrhythmias. This study aims to profile BS and GS patients followed at our hospital, focusing on cardiological phenotyping. We assessed diagnostic, clinical, and lab data, particularly examining the link between electrolyte imbalances (like hypokalemia or hypomagnesemia) and electrocardiographic changes or cardiac symptoms during follow-up. Method We screened all BS and GS patients for study inclusion, requiring a genetic diagnosis with disease-causing mutations and comprehensive clinical and electrocardiographic data. We excluded cases lacking sufficient data. We gathered demographic and health information retrospectively, categorizing patients based on electrocardiographic results into groups: 1) persistent long QT interval, 2) transient long QT interval, and 3) no long QT interval. Data were summarized with medians, interquartile ranges, and frequencies. Results A total of 27 patients were enrolled in the study, 16 with Bartter Syndrome (BS) and 11 with Gitelman Syndrome (GS); median length of follow-up was 6 years (range 3-19). Only one patient was classified in group 1, with a constant QTc prolongation (446.3 ms); 8 patients (34.8%) fell into group 2 with median QTc values of 420 ms, all exhibiting hypokalemia and hypomagnesemia. The majority (14/23, 61%) were in group 3, with a median QTc of 399.2 ms and 79% displaying hypokalemia and hypomagnesemia. All 9 patients who experienced cardiac-related symptoms were adults, with 8 presenting these symptoms during intercurrent episodes. The study also compared clinical differences between BS and GS patients, noting a higher frequency of hypokalemia and hypomagnesemia in GS, whereas BS patients had more electrocardiographic alterations, although not statistically significant. No echocardiographic abnormalities were detected from the available data, and there were no recorded incidents of malignant arrhythmias or sudden death. Conclusion Electrocardiographic abnormalities in BS and GS patients fluctuate, often related to episodic events, with QT prolongation in one-third of cases but no severe cardiac complications, indicating a generally positive prognosis.

Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome.

Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD). During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups. The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.

Corrected QT Interval and Outcomes of Dialysis Patients with Symptomatic Peripheral Artery Disease: A Prospective Cohort Study

Background: Peripheral artery disease (PAD) is common and associated with a higher risk of cardiovascular morbidity and mortality in dialysis patients. A longer corrected QT (QTc) interval has been associated with adverse cardiovascular events and mortality in the general population and patients with end-stage kidney disease. However, little evidence is available on the predictive value of QTc in dialysis patients with PAD. Methods: We conducted a prospective cohort study of 356 dialysis patients with symptomatic PAD undergoing endovascular therapy. We performed the resting 12-lead electrocardiogram (ECG) at baseline. Cox regression analyses were used to assess the association of QTc with all-cause mortality and major adverse cardiovascular events (MACEs), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: The mean age was 67.3 ± 11.5 years; 41.6% of participants were women. The median QTc was 471 (interquartile ranges 448–491) milliseconds (ms). During a median follow-up of 2.2 years, 188 (52.8%) patients died, and MACEs occurred in 119 (33.4%) patients. In multivariable-adjusted models, patients in tertile 3 of QTc levels had a significantly greater risk of all-cause mortality (hazard ratio [HR] 2.41, 95% confidence intervals [CI] 1.58–3.69) and MACEs (HR 1.90, 95% CI 1.15–3.13) than those in tertile 1. Similarly, each 10-ms increase in the baseline QTc predicted a higher risk of all-cause death (HR 1.15, 95% CI 1.09–1.21) and MACEs (HR 1.15, 95% CI 1.07–1.23). Conclusions: QTc prolongation was independently associated with adverse outcomes among dialysis patients with symptomatic PAD.

Roles of atrial arrhythmias in triggering torsade de pointes in patients with acquired long QT syndrome

Abstract Background Little is known about a role of atrial arrhythmias (AAs) in triggering Torsade de Pointes (TdP) in patients with long QT syndrome (LQTS). Purpose To determine the prevalence of AAs-induced TdP in acute acquired LQTS patients and to classify the AAs’ roles in the development of TdP. Methods Initiation patterns of 81 episodes of TdP obtained from 34 consecutive acquired LQTS patients (14 men; median age, 69 years; median QTc, 645.5 ms) with documented TdP were analysed. The patients were divided into 2 groups based on the presence or absence of AAs involvement in triggering TdP: AAs-induced and non-AAs-induced groups. Results AAs-induced group comprised 52.9% (18/34) of the patients studied. TdP was preceded by AAs-induced short-long sequences (SLSs) in 41.2% (14/34) of the patients and directly induced by R-on-T AAs (AAs coincidentally encounter a vulnerable repolarizing region during the T wave) in 23.5% (8/34). AAs-induced group experienced TdP after initiating therapy more frequently than non-AAs-induced group (2.5 vs. 1, p=0.008). AAs triggered 48 (59.3%) of the 81 TdP episodes. AAs-induced SLS comprised 67.8% (40 /59) of the SLS-induced TdP episodes. R-on-T AAs accounted for 23.5% (19/81) of the TdP episodes. Conclusions Our observations suggest that AAs are associated with the onset mechanism of TdP in more than half of acute acquired LQTS patients and even increase TdP frequency. Thus, AAs are not benign but rather can be lethal in acute acquired LQTS patients.Representative casesAnalysis of Torsade de Pointes episodes

Abstract 11749: Identifying Infants With Long QT Syndrome Type 1: Looking Beyond the QTc

Background: Abnormal repolarization in long QT syndrome type 1 (LQT1) is characterized by QT prolongation and abnormal T-waves. In the absence of familial disease, LQT1 is easily missed in infants as the QTc is often normal, exposing children to life-threatening arrhythmia. Hypothesis: T-wave morphology metrics are superior to QTc for diagnosis of LQT1. Aim: Compare quantifiable aspects of T-wave morphology and QTc to differentiate infants with and without LQT1. Methods: Infants aged 0.5-6 months with a pathogenic/likely pathogenic KCNQ1 variant were compared to age/sex-matched controls in a 1:2 ratio. Measurements were made in leads II/V5. T-wave morphology was assessed by J-point to T-wave peak (J-Tp) and Tp to T-wave end (Tp-Te). Bazett’s formula was used to correct for heart rate and Te defined using the tangent method. Results: We identified 34 LQT1 infants and 68 controls. The median (IQR) QTc was 457 (430-476) ms for LQT1 cases and 402 (392-420) ms for controls (p&lt;0.001). The 98%tile QTc for controls was 448 ms and 13/34 (38%) LQT1 cases were below this value. In lead II, LQT1 cases had a significantly longer rate corrected J-Tp compared to controls, 294 (272-312) ms v. 222 (211-234) ms (p &lt;0.001) and shorter Tp-Te, 71 (60-80) ms v. 85 (75-95) ms (p&lt;0.001). The J-Tp/Tp-Te ratio was 0.25 in LQT1 cases and 0.39 in controls (p&lt;0.001). Findings were similar in V5. V5 rate corrected J-Tp best discriminated between LQT1 cases and controls (ROC AUC 0.99, optimal cut point ≥256ms) and outperformed QTc (AUC 0.92). This remained true in those with QTc &lt;98%tile (AUC 0.98). Measurements in a subset of 30 infants made by 3 ECG readers showed superior reliability for J-Tp in leads II and V5 (ICC coefficient 0.92) compared to QTc (0.88). Conclusions: Nearly 40% of infants with LQT1 have a normal a QTc, yet a significantly abnormal and quantifiable T-wave morphology. J-Tp and Tp-Te are reliable and reproducible measurements and should be included in the assessment of potential infantile LQT1.

Abstract 18336: Accuracy of Antiarrhythmic Drug Dosing Using a Computer-Guided Decision Tree Model

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder and often requires inpatient monitoring for antiarrhythmic drug (AAD) initiation, specifically for dofetilide and sotalol. No system currently offers safe at-home AAD initiation, which is needed to expand AAD access for low-risk or underserved patients and reduce mortality. Objective: Assess accuracy of AAD dosing using a computer-guided decision tree algorithm compared to physician dosing decisions. Methods: Patients in an all-comer population were instructed to take a mobile ECG (mECG; KardiaMobile 6L, AliveCor). A proprietary ML algorithm (SafeBeat Rx) interpreted QTc for each mECG and recommended a starting dose for each AAD (dofetilide and sotalol), per drug labeling. For sotalol, an initial dose of 80 mg was recommended if QTc ≤ 450 ms and HR &gt; 60 bpm; if baseline ECG criteria were unmet, 0 mg was recommended. For dofetilide, initial 500 mcg dose was recommended if QTc ≤ 440 ms. For software simulation, creatinine clearance was assumed to be normal (&gt;60 mL/min) for all patients. Recommendations were adjusted based on a higher QTc threshold &gt;550 ms if the patient’s baseline ECG showed wide QRS (e.g. artificially paced, bundle branch block). The software recommendations were compared to the gold standard: dosing selected by 2 physicians manually measuring baseline mECG QTc and selecting a theoretical starting dose accordingly, independent from software-generated results. Results: 95 patients were enrolled (40% healthy, 30% outpatients, 30% inpatients). The algorithm was highly accurate in predicting starting dose; agreement with physicians was 94.68% for sotalol and 95.74% for dofetilide. Median heart rate was 84.8 bpm (SD = 17.5) and median QTc interval was 475.5 ms (SD = 106.4). Physicians chose the manufacturer-recommended full starting dose for 85% of patients for sotalol and 86% for dofetilide, compared with 86% for sotalol and 86% for dofetilide recommended by the software. Conclusion: The decision tree model had 95% agreement with physician dose recommendations, demonstrating that the algorithm can accurately guide patient-specific AAD dosing, which helps guide remote physician-directed initiation of AAD, ultimately expanding drug access for AF patients.

Acute Mesenteric Ischemia: The Diagnostic Value of QT Parameters and their Relationship with CT Findings.

One of the greatest challenges in the diagnosis of acute mesenteric ischemia (AMI) is the lack of specific laboratory tests that support multidetector computed tomography (CT). Our aim is to investigate the diagnostic value of electrocardiographic QT parameters in AMI and their relationship with CT findings. Patients who were admitted to the emergency department with abdominal pain were recruited retrospectively from the hospital information system. Grouping was carried out on the basis of AMI (n=78) and non-AMI (n=78). In both groups, the corrected QT (QTc) and QT dispersion (QTD) were measured on electrocardiographs, and the qualitative and quantitative CT findings were evaluated on CT examinations. The QTc and QTD values were higher in the AMI group. The median QTc values were 456.16 (IQR: 422.88-483.16) for the AMI group and 388.83 (IQR: 359.74-415.83) for the control group (p<0.001), and the median QTD values were 58 (IQR: 50.3-68.25) for the AMI group and 46 (IQR: 42-50) for the control group (p<0.001). In the CT analysis, the QTc values were significantly higher among AMI patients, with images of paper-thin bowel walls and the absence of bowel wall enhancement (p=0.042 and p=0.042, respectively). Meanwhile, the QTD values were significantly higher among patients with venous pneumatosis findings on CT (p=0.005). In the regression analysis, a significant relationship was found between the QT parameters and AMI (p<0.001). For QTc, an AUC of 0.903 (95% CI: 0.857-0.950, p<0.001), a sensitivity of 80.8%, and a specificity of 82.3% were found. For QTD, an AUC of 0.821 (95% CI: 0.753-0.889, p<0.001), a sensitivity of 73.1%, and a specificity of 82.3% were found. We found the QTc and QTD values to be significantly higher among AMI patients. Furthermore, we found a significant relationship between the CT findings and QTc and QTD and a significant relationship between survival and QTc in the AMI group.

Sodium bicarbonate treatment for QRS widening in bupropion overdoses

Introduction Bupropion cardiotoxicity widens QRS complexes by inhibiting cardiac gap junctions. Sodium bicarbonate is the standard treatment for QRS widening from sodium channel blockade, but its effect on QRS widening in bupropion cardiotoxicity is not well-studied. Methods This is a retrospective cohort study of bupropion overdoses from 10 hospitals between January 2010 and June 2022. Patients with documented administration of sodium bicarbonate and QRS duration > 100 milliseconds on pre-bicarbonate electrocardiogram were included. Patients with no electrocardiogram within four hours of treatment or with baseline pre-overdose wide QRS and < 10 milliseconds widening from baseline were excluded. The primary outcome was a change in QRS duration between the pre-bicarbonate electrocardiogram and the first electrocardiogram after initial bicarbonate administration. Secondary outcomes included prevalence of post-bicarbonate QRS < 100 milliseconds, change in electrocardiogram intervals after total bicarbonate administration, and change in metabolic parameters and hemodynamics. Wilcoxon signed-rank testing was performed on the primary outcome. Linear regression modeling was performed to test for an association between change in QRS and bicarbonate dosing. Results Thirteen patients were included for final analysis. The median age was 32 years, and 54% were male. Six patients developed seizures; one developed ventricular tachycardia, and four received vasopressors. The median QRS and QTc pre-bicarbonate were 116 and 495 milliseconds, respectively. The median change in QRS duration was −2.0 milliseconds, which was not statistically significant (P = 0.42). The median bicarbonate dose administered before the first post-bicarbonate electrocardiogram was 100 milliequivalents. We did not identify an association between QRS change and bicarbonate dosing (P = 0.9, R-squared = 0.001). No patient had a QRS duration < 100 milliseconds after the initial bicarbonate dose. There was minimal change in QTc, electrolytes, heart rate, or blood pressure; alkalemia post-bicarbonate was achieved in eight patients. Conclusion Sodium bicarbonate did not significantly decrease QRS duration in this small retrospective cohort of bupropion overdoses.

Management of cardiac arrhythmias in paediatric patients with TANGO2-deficiency disorder

Abstract Funding Acknowledgements Type of funding sources: None. Background TANGO2-deficiency disorder (TDD) is a rare paediatric condition caused by bi-allelic mutations in the TANGO2 gene. TDD is characterised by susceptibility to metabolic crises with rhabdomyolysis, encephalopathy, lactic acidosis, hypothyroidism and difficult to manage tachyarrhythmias. Aim We describe the electrocardiographic (ECG) findings at baseline and during metabolic crises in patients with TDD. Methods Retrospective, single-centre, case series study of patients with TDD (&amp;lt;18 years), with ECG and subcutaneous Holter monitoring, both during metabolic crises and compensated phases. Results During the period 2013-2021, 12 patients with TDD were found (median age 6.8 years, IQR 2-11.5 years). In the inter-crisis period, bradyarrhythmias were evidenced: 2/12 patients presented sinus bradycardia, 2/12 pauses of 4 and 10 seconds, 1/12 Wenckebach type block; and tachyarrhythmias: 1/12 presented paroxysmal supraventricular tachycardia and 1/12 flutter. 25% had long QT during non-acute phases (median QTc max 476 ms, IQR 456ms-530ms). There were 14 hospitalisations for metabolic crises. 57.1% had QTc interval prolongation, 35.7% ventricular tachycardias (4/14 monomorphic VT, 1/14 torsade de prongs) and 1/14 Brugada type 3 pattern. Three patients died in the context of severe metabolic acidosis and multi-organ involvement (2/12 due to VT and 1/12 due to cardiogenic shock, bradycardia associated with QTc of 635ms and severe ventricular dysfunction). Conclusions In paediatric patients with TDD, the most frequent ECG abnormality was QTc interval prolongation with or without metabolic crises. There is a high risk of tachyarrhythmias, mainly VT, being the main cause of death in children with TDD. Subcutaneous Holter monitoring is recommended. During metabolic crises, there should be close ECG monitoring.

Repolarization abnormalities and outcomes following return of spontaneous circulation after cardiac arrest

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Boston Medical Center Background Prolongation of ventricular repolarization, as measured by the corrected QT interval (QTc), is common in patients resuscitated from cardiac arrest and is exacerbated by targeted temperature management. In this population, QTc prolongation appears to be transient and may not be associated with risk for malignant arrhythmia. The T-peak to T-end interval (TpTe), which represents transmural dispersion of repolarization in the left ventricle, is an emerging marker of risk for sudden cardiac death. Purpose We sought to evaluate the association of prolonged QTc and TpTe with in-hospital mortality and favorable neurologic outcome at discharge in comatose survivors of cardiac arrest. Methods We conducted a retrospective analysis of patients enrolled in the Multimodal Outcome CHAracterization in cardiac arrest patients (MOCHA) study at a single academic center. Participants were comatose survivors of cardiac arrest aged 18-89 years who had an electrocardiogram (ECG) obtained after return of spontaneous circulation between 2011-2020. Prolonged QTc was defined as QTc &amp;gt;450 ms in males and QTc &amp;gt;460 ms in females as measured by automated algorithm. Prolonged TpTe was defined as TpTe &amp;gt;90 ms as measured by two trained assessors. The primary outcomes were in-hospital mortality and favorable neurologic outcome at hospital discharge (Cerebral Performance Category 1-2). Multivariable logistic regression, adjusted for age, medical comorbidities (diabetes, chronic kidney disease, heart failure, malignancy) and arrest characteristics (location, initial rhythm, witnessed status, bystander CPR) was used to test the association between QTc prolongation and TpTe prolongation and outcomes. Results 471 (89.0%) patients met inclusion criteria and were included in this analysis; 58 (11.0%) were excluded due to missing post-ROSC ECG. The median age was 62 years (Interquartile range (IQR): 51-73 years), and 284 (60.4%) were male. 297 (63.2%) presented with out-of-hospital cardiac arrest and 138 (29.4%) presented with a shockable rhythm. The median QTc was 479 ms (IQR: 445-517 ms) and the median TpTe was 82.5 ms (IQR: 66-102 ms). Patients with and without prolonged QTc had similar incidence of mortality (71.2% vs 65.5%, P=0.22) and favorable neurologic outcome (22.4% vs 26.9%, P=0.29). Mortality was higher among patients with prolonged TpTe (75.4% vs 65.8%, P=0.03), which persisted after multivariable adjustment (OR 1.91; 95% CI: 1.20-3.04, P&amp;lt;0.01). Patients with prolonged TpTe had lower incidence of favorable neurologic outcome (18.3% vs 27.1%, P=0.03), which persisted after multivariable adjustment (OR 0.47; 95% CI: 0.28-0.79, P&amp;lt;0.01). Conclusion TpTe prolongation, but not QTc prolongation, was independently associated with higher mortality and worse neurologic outcome in comatose survivors of cardiac arrest. Further research is needed to clarify the clinical significance of repolarization abnormalities in patients presenting with cardiac arrest.

QT interval and short-term outcome in acute heart failure

ObjectiveTo investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF).MethodsWe analyzed AHF patients enrolled in 11 Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a QTc = 450 ms as reference.ResultsOf 1800 patients meeting entry criteria (median age 84 years (IQR = 77–89), 56% female), their median QTc was 453 ms (IQR = 422–483). The 30-day mortality was 9.7%, while need of hospitalization, in-hospital mortality and prolonged hospitalization were 77.8%, 9.0% and 50.0%, respectively. RCS curves found longer QTc was associated with 30-day mortality if > 561 ms, OR = 1.86 (1.00–3.45), and increased up to OR = 10.5 (2.25–49.1), for QTc = 674 ms. A similar pattern was observed for in-hospital mortality; OR = 2.64 (1.04–6.69), for QTc = 588 ms, and increasing up to OR = 8.02 (1.30–49.3), for QTc = 674 ms. Conversely, the need of hospitalization had a U-shaped relationship: being increased in patients with shorter QTc [OR = 1.45 (1.00–2.09) for QTc = 381 ms, OR = 5.88 (1.25–27.6) for the shortest QTc of 200 ms], and also increasing for prolonged QTc [OR = 1.06 (1.00–1.13), for QTc = 459 ms, and reaching OR = 2.15 (1.00–4.62) for QTc = 588 ms]. QTc was not associated with prolonged hospitalization.ConclusionIn ED AHF patients, initial QTc provides independent short-term prognostic information, with increasing QTc associated with increasing mortality, while both, shortened and prolonged QTc are associated with need of hospitalization.Graphical abstract

Abstract WMP70: Young Adults With Cryptogenic Ischemic Stroke Have Longer Corrected QT Intervals Than Healthy Controls

Introduction: In cryptogenic ischemic stroke, no definite etiology is found and high-risk cardiac sources of embolism are excluded. However, it has been hypothesized that many cryptogenic strokes could be cardioembolic especially in younger patients. We assessed whether resting ECG could reveal cardiac differences in young patients with cryptogenic ischemic stroke, as compared to healthy controls. Methods: We recruited prospectively 477 patients with cryptogenic ischemic stroke at age 18-49 and 455 controls at 19 European tertiary centers. We obtained vast clinical data and resting 12-lead ECG (at subacute phase from patients). From the ECGs we measured heart rate, presence of conduction blocks, QRS transition zone in precordial leads, presence of abnormal T-wave inversions, presence of ST depression and corrected QT-interval (QTc). We constructed multivariate models for each ECG parameter, adjusting for demographic and clinical data, using binomial logistic regression. Results: Median age for both patients and controls was 41 years, with 54.0% of patients and 54.6% of controls being men. Compared to controls, patients had higher prevalence of hypertension (38.8% vs. 30.0%, P=0.005) and obesity (38.8% vs. 30.1%, P=0.005), were more frequently heavy drinkers (14.6% vs. 7.6%, P&lt;0.001), and were more likely to smoke (34.1% vs. 17.5%, P&lt;0.001). Patients with cryptogenic ischemic stroke had longer QTc interval than controls (median QTc 416ms vs. 409ms, P&lt;0.001). After adjustments, longer QTc interval was associated with stroke (odds ratio 1.12 per 10ms increase, P&lt;0.001). There were no statistically significant differences in other ECG-abnormalities between patients and controls. Conclusion: Young patients with cryptogenic ischemic stroke have a longer corrected QT interval than healthy controls. The reason for this novel finding is unclear, and could reflect both underlying cardiogenic and neurogenic reasons.