Marker Of Ventricular Repolarization Research Articles

The Relationship between Frontal QRS-T Angle and Vitamin D Deficiency.

Background and Objectives: A deficiency in serum 25-hydroxyvitamin D levels is associated with a number of cardiovascular situations, such as high blood pressure, heart failure, atherosclerotic heart disease, and peripheral artery disease. The frontal QRS-T angle has recently been proposed as a marker of ventricular repolarization. A wider frontal QRS-T angle has been positively correlated with adverse cardiac events. The objective of our study was to examine the association between serum 25-hydroxyvitamin D level and the frontal QRS-T angle. Materials and Methods: A total of 173 consecutive patients aged 18-60 years undergoing routine cardiology check-up evaluation, and not receiving concurrent vitamin D treatment were included in the study. Patients were classified in three groups, depending on their vitamin D levels, and categorized as follows: Group 1-deficient (<20 ng/mL), Group 2-insufficient (20-29 ng/mL), or Group 3-optimal (≥30 ng/mL). The frontal QRS-T angle was determined using the automated reports generated by the electrocardiography machine. Results: The average age of participants was 45.8 (±12.2) years, and 55.5% of participants were female (p < 0.001). Individuals with low vitamin D concentrations exhibited a wider frontal QRS-T angle. It was determined that vitamin D level is an independent predictive factor for the frontal QRS-T angle. Conclusions: As the levels of 25-hydroxyvitamin D decrease, repolarization time assessed by frontal QRS-T angle is widened. Our findings indicate that lower concentrations of vitamin D may increase the susceptibility to ventricular arrhythmia.

Predicting Long-Term Ventricular Arrhythmia Risk in Children with Acute Lymphoblastic Leukemia Using Normal Values of Ventricular Repolarization Markers Established from Japanese Cohort Study.

Cardiac complications due to anthracycline treatment may become evident several years after chemotherapy and are recognized as a serious cause of morbidity and mortality in cancer patients or childhood cancer survivors. We analyzed ventricular repolarization parameters in electrocardiography for pediatric acute lymphoblastic leukemia patients during chemotherapy and in long-term follow-up. To establish the reference values of ventricular repolarization parameters in children, we retrospectively summarized the Tpe interval, QT interval, QTc interval, and Tpe/QT ratio in healthy Japanese children. Electrocardiography data recorded from students in 1st and 7th grades were randomly selected from a database maintained by the school-based screening system in the Oita city cohort, Japan. Subsequently, chronological data of the Tpe/QT ratio in 17 pediatric patients with acute lymphoblastic leukemia were analyzed over time. The mean ± standard deviation of the Tpe interval in 1st and 7th graders was 70 ± 7 and 78 ± 17 ms, respectively, while the mean ± standard deviation of the Tpe/QT ratio was 0.21 ± 0.02 and 0.22 ± 0.02 ms, respectively. During the intensive phase of treatment, the Tpe/QT ratios of 3 high-risk patients among the 17 patients with acute lymphoblastic leukemia exceeded the upper limit. The Tpe/QT ratio has a potential clinical application in predicting the risk of long-term ventricular arrhythmia of cancer patients or childhood cancer survivors from childhood to adulthood.

DETERMINING THE RISK OF CARDIOVASCULAR DISEASE IN PATIENTS DIAGNOSED WITH SCHIZOPHRENIA AND BIPOLAR AFFECTIVE DISORDER.

In Schizophrenia (SCZ) and Bipolar Affective Disorder (BAD) patients using the Framingham Heart Risk Scoring (FHRS), we aimed to investigate the possible cardiac arrhythmia risk by calculating electrocardiogram (ECG) parameters (QT, QTc, Tpe, and TPE/QTc ratios), which are ventricular repolarization markers. A total of 140 BAD and 253 SCZ patients were included in the study. Age, blood test results (fasting blood glucose, LDL-HDL-TC levels, hemogram values), blood pressure and heart rate, smoking status, antihypertensive drug use, and FHRS were calculated from the patient files, and sociodemographic information was recorded. In addition, ECG calculations were performed, and QT, QTc, TPe, TPe/QTc ratios and heart rate were measured. When we evaluated the cardiac risk indexes of SCZ and BAD patients, we detected that FHRS was higher in smokers, female patients, and those with other medical diseases such as diabetes mellitus (DM) (p<0.05). In addition, we found that QTc rates, markers of ventricular repolarization, were associated with FHRS, the number of antipsychotics used, patient age, disease duration, and the number of hospitalizations. TPe and QT rates were found to increase in parallel with FHRS. In addition, a positive correlation was found between QTc rates in females, patients with DM, and those using additional medical drugs. (p<0.05) In BAD and SCZ patients, diabetes diagnosis, other medical drug use, a high Framingham heart score, the number of antipsychotics, the disease duration, the patient&apos;s age, and an increased number of hospitalizations may increase the risk of cardiac arrhythmia. Therefore, possible cardiac risk should be considered in patients with chronic drug use, such as BAD and SCZ. Regulating the treatment and follow-up of this group of patients against possible cardiac risks will reduce cardiac mortality and morbidity

Cardio-ankle brachial index is associated with prolonged Tp-e interval in patients with arterial hypertension.

The cardio-ankle vascular index (CAVI) is a marker of arterial stiffness, and elevated CAVI values have been reported to be associated with an increased risk of cardiovascular mortality and cardiac arrhythmia. This study aimed to evaluate the relationship between Tp-e interval and CAVI, which is associated with cardiac arrhythmia on electrocardiography (ECG). The study included patients with hypertension whose blood pressure values were taken under control with optimal medical treatment. Arterial stiffness and CAVI were measured using the vascular scanning system VaSera VS-1000. The patients were divided into two groups as CAVI<9 and CAVI≥9. Ventricular repolarization markers QT and QTc intervals, Tp-e interval, and Tp-e/QT and Tp-e/QTc ratios were measured using 12‑lead ECG. Tp-e interval (78.7±10.3 vs. 63.6±9.1, p<0.001), Tp-e/QT ratio (0.018±0.02 vs. 0.015±0.02, p<0.001), and Tp-e/QTc ratio (0.17±0.02 vs. 0.14±0.04, p=0.025) were statistically significantly higher in the CAVI≥9 group compared to the CAVI<9 group. In the prediction of patients in the CAVI≥9 group, Tp-e interval had an area under the curve value of 0.862 (0.784-0.940, p<0.001) at the cut-off point of >72.5msec, indicating a statistically significant result. Left CAVI and right CAVI were found to be significantly correlated with Tp-e interval (r=-0.650, p<0.001 and r=-0.663, p<0.001, respectively). We found that elevated CAVI values were associated and positively correlated with prolonged Tp-e interval values in patients with hypertension. Patients with elevated CAVI values should be followed up closely to prevent cardiac arrhythmic events.

Evaluation of novel ventricular repolarization parameters in patients with acromegaly

Objectives: T wave’s peak and end interval (Tp-e), Tp-e/QT ratio and Tp-e/QTc ratio are novel markers of ventricular repolarization and are associated with ventricular arrhythmias. Increased ventricular arrhythmia incidence is reported in patients with acromegaly. The purpose of this study is to evaluate ventricular repolarization using the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio in patients with acromegaly. Methods: Thirty-five patients with acromegaly were included in the study. The control group was consisted of forty-one subjects without acromegaly that having similar age, sex ratio and comorbidities. The Tp-e interval, Tp-e/QT ratio, Tp-e/QTc ratio, and other ventricular repolarization parameters of all patients were evaluated using electrocardiography. Results: Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were significantly prolonged in patients with acromegaly compared to the control group. Furthermore, Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio showed a significant correlation with plasma GH levels and LVMI values. Conclusions: Our study revealed that Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with acromegaly. We believe that the Tp-e interval, Tp-e/QT ratio, and Tpe/QTc ratio can be used in the evaluation of increased cardiovascular risk in patients with acromegaly.

Evaluation of Ventricular Repolarization Markers and Fragmented QRS in Patients with Bipolar Disorder

Evaluation of Ventricular Repolarization Markers and Fragmented QRS in Patients with Bipolar Disorder

Effect of Sodium-Glucose Co-transporter-2 Inhibitors on Ventricular Repolarization Markers in Heart Failure with Reduced Ejection Fraction.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors added to optimal medical therapy have been shown to reduce the risk of cardiovascular death and recurrent heart failure (HF) hospitalization in HF patients. We aimed to evaluate the effect of SGLT2 inhibitors on the ventricular repolarization markers (VRM) in patients with HF with reduced ejection fraction (HFrEF). 51 patients with HFrEF who had symptoms New York Heart Association (NYHA) class II-IV despite optimal medical treatment and were added SGLT2 inhibitors to their treatment were included in the study. Electrocardiography (ECG) and laboratory results obtained before the treatment and at the first-month follow-up visit were compared. QT, QTc (corrected by Bazett formula), QT dispersion (QTd), QTc dispersion (QTc-d), Tpeak to Tend (Tp-e) interval, Tp-e/QT, and Tp-e/QTc ratios were measured and defined as VRM. A significant decrease was observed in HR, QT, QTc intervals, and QTd compared to pre-treatment. While the mean Tp-e interval was 101.5 ± 11.7ms before treatment, it decreased to 93.1 ± 12.7ms after treatment (p < 0.001). There was a significant decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels after treatment [2859 ± 681vs.1266 ± 763, respectively (p < 0.001)] and QTd, Tp-e interval, and Tp-e/QTc ratio was positively correlated with the change in NT-proBNP level. The addition of SGLT2 inhibitors to optimal medical therapy in HFrEF patients positively changes VRM (QT, QTc, QTd, Tp-e, and Tp-e/QTc).

Relationship between subclinical hyperthyroidism and ventricular repolarization markers

Objective: To evaluate repolarization defects and arrhythmogenic predisposition through ventricular repolarization markers in patients with subclinical hyperthyroidism (sHT).&#x0D; Materials and Methods: Patients with asymptomatic endogenous sHT and healthy participants with similar age and demographic characteristics were included in our study. Laboratory tests and echocardiographic evaluations were performed. Specific ventricular repolarization markers,such as QT, QTc (corrected QT inteval by Bazett formula) dispersion, Tpeak-Tend (Tp-e) interval, and Tp-e/QT and Tp-e/QTc ratios were obtained with manually on electrocardiograpy.&#x0D; Results: A total of 90 participants were included in our study. The mean age was 59.04±13.28 years for the 45 patients in the sHT group and mean 57.13±15.87 years for the 45 controls. The PR, QT and QTc dispersions were found to be significantly higher in the sHT group (p

0782 Changes in markers of ventricular repolarization and positive airway pressure therapy: A pilot study

Abstract Introduction Positive airway pressure (PAP) therapy is the mainstay treatment for obstructive sleep apnea (OSA). Continuous PAP (CPAP) therapy has been shown to decrease QTc length in electrocardiograms in patients with OSA in small studies. The impact of higher pressures of CPAP and Bilevel PAP (BPAP) on ventricular repolarization—QTc length and QT variability in OSA is unknown. The goal of this pilot study is to explore this relationship. Methods 10 consecutive patients who underwent polysomnography during which they had a diagnostic, CPAP titration, and BPAP titration portion were included for analysis. Bazett’s heart rate correction was used to calculate QTc. QT variability was measured as short-term interval QT variability (STVQT) and normalized QT interval variance (QTVN). All variables were analyzed for the entire duration of the diagnostic period, on the highest CPAP pressure and highest BPAP pressure delivered. Results The patients were 49 ± 15 years of age and 60% women. Median CPAP pressure was 14.5 cm H2O (mean 13.5 ± 5 cm H2O). For BPAP, the median inspiratory PAP was 21.5 cm H2O (mean 20.5 ± 5 cm H2O) and EPAP median was 16 cm H2O (mean 15.9 ± 4 cm H2O). Mean QTc for the diagnostic portion, highest CPAP pressure and highest BPAP pressure were 430 ± 17 ms, 445 ± 15 ms and 441 ± 21 ms, respectively (p=0.141). Mean QTVN for the diagnostic portion, highest CPAP pressure and highest BPAP pressure settings were 0.0011 ± 0.0008 dimensionless units (du), 0.0012± 0.0008 du and 0.002 ± 0.0012 du, respectively (p=0.127). STVQT for the diagnostic portion, highest CPAP pressure and highest BPAP pressure settings were 6.62 ± 4.13 ms, 9.12 ± 4.7271 ms and 12.62 ± 4.99 ms, respectively (P=0.041). Post-hoc pairwise comparisons between BPAP and diagnostic portions of the study were significant for STVQT (P=0.034). Conclusion Short-term QT variability, STVQT, was significantly increased on BPAP when compared to the diagnostic portion of the study. Support (If Any) American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140, 2L30HL154400-023) University of Arizona Health Sciences Career Development Award (5299903), and University of Arizona Faculty Seed Grant (5833261)

Markers of ventricular repolarization and overall mortality in sleep disordered breathing

IntroductionVariability and prolongation of ventricular repolarization – measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. MethodsEight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. ResultsEight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). ConclusionSleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

Examination of New Electrocardiographic Repolarization Markers in Diabetic Patients with Noncritical Coronary Artery Disease.

Background Diabetes mellitus (DM) is a multisystemic, chronic disease that affects many organs. Coronary artery disease (CAD) is the leading cause of death in patients with DM. The electrocardiogram's new ventricular repolarization parameters can predict mortality and morbidity. The ventricular repolarization indices were examined in diabetic patients with a CAD diagnosis in this study. Methods The study group consisted of 84 DM patients (51 males; mean age 58.8 ± 6.6) with noncritical CAD. The control group consisted of 84 DM patients (47 males; mean age 58.7 ± 8.8) with a normal coronary artery. The intervals of QT, QRS, JT, and Tp-e were all measured. Tp-e/QT, Tp-e/QTc, Tp-e/JT, and Tp-e/JTc ratios were determined with QTc, QTd, QTdc, and JTc intervals. Results Heart rate (74.4 ± 13.1 vs. 70.0 ± 13.6 bpm, p: 0.036), QT (381.0 ± 30.3 vs. 368.6 ± 29.1 ms, p: 0.008), QTc (407.5 (359–450) vs. 389 (339–430) ms, p < 0.001), QTd (25.1 ± 6.2 vs. 21.9 ± 9.9 ms, p: 0.013), QTdc (26.7 ± 6.1 vs. 23.1 ± 10.8 ms, p: 0.010), Tp-e (95.7 ± 12.2 vs. 73.6 ± 9.8 ms, p < 0.001), JT (293.8 ± 22.0 vs. 283.5 ± 30.9 ms, p: 0.014), and JTc (313.6 ± 12.3 vs. 302.4 ± 33.7 ms, p=0.005) intervals, and Tp-e/QT (0.25 ± 0.03 vs. 0.20 ± 0.03 ms, p < 0.001), Tp-e/QTc [0.23 (0.19–2.33) vs. 0.19 (0.14–0.25) ms, p=0.007], Tp-e/JT (0.33 ± 0.04 vs. 0.26 ± 0.04 ms, p < 0.001), and Tp-e/JTc (0.30 ± 0.03 vs. 0.24 ± 0.03 ms, p < 0.001) ratios were all found to be significantly higher in diabetic patients with noncritical CAD. Conclusion In this study, ventricular repolarization markers on the surface ECG were found to be elevated in diabetic CAD patients. These variables may be related to fatal arrhythmic events. To be sure, large-scale, randomized controlled trials are required.

Tp-e interval and Tp-e/JT ratio before and after catheter ablation in patients with Wolff Parkinson White syndrome

Aim: Tp-e and Tp-e/QT are novel markers of ventricular repolarization. However, preexcitation in Wolff Parkinson White (WPW) syndrome may preclude accurate measurement of repolarization as assessed by the QT. We aimed to research the assessment of Tp-e and Tp-e/JT before and after ablation in WPW.&#x0D; Material and Method: We enrolled 50 consecutive patients with symptomatic WPW syndrome who underwent catheter ablation of their accessory pathways for treatment. All of the patients were successfully ablated. ECGs were performed before the procedure and repeated after the ablation procedure.&#x0D; Results: Tp-e (86.6±16.2 vs 80.6±12.5; p=0.021) and Tp-e(c) (96.7±18.9 vs 88.3±11.2; p=0,005) showed a significant decrease after the procedure. Tp-e/JT (0.307±0.053 vs 0.279±0.040; p=0.001) and Tp-e/JT(c) (0.276±0.048 vs 0.255±0.045; p=0.009) showed a significant decrease after the procedure. There was a significant association between ERP and before procedure Tp-e (c) (r=- 0.370, p=0.008) and Tp-e/JT (r=- 0.371, p=0.008).&#x0D; Conclusion: This study demonstrated that Tp-e and Tp-e/JT were significantly diminished in WPW after the ablation.

Electrocardiographic markers of ventricular repolarization in the obese population: A descriptive review

Abstract Obesity is a global epidemiological problem that significantly contributes to the development of cardiovascular diseases. It is a proven factor for an increased risk of overall mortality and the occurrence of sudden cardiac death (SCD). The disease is accompanied by a structural and functional myocardium remodeling, which often results in ventricular repolarization abnormalities and contributes to the triggering of life-threatening arrhythmias. This heightened state of readiness for proarrhythmia is the cause of the sudden cardiac deaths which are recorded in this group of patients and which often constitute the first manifestation of ongoing cardiac pathology. One of the reasons for these arrhythmias may be abnormalities of ventricular muscle repolarization. In this descriptive review, we demonstrate electrocardiographic markers of ventricular repolarization (J point, QT/QTc/QTc-d, JT/JTc/JTc-d, ST segment, T wave and Tp-e/Tp-ed/Tp-e/QT), analyze their abnormalities in the obese population, and discuss their changes after weight loss.

The relationship between vitamin B12 levels and electrocardiographic ventricular repolarization markers.

Background: it has been shown that vitamin B12 deficiency, which can cause hematological and neuropsychiatric disorders, may also be associated with cardiac autonomic dysfunction, heart rate variability, endothelial dysfunction, and a decrease in myocardial deformation. Aims: the aim of our study is to evaluate the relationship between vitamin B12 levels and electrocardiographic repolarization disorders, which are indicators of arrhythmogenic predisposition in healthy individuals. Methods: our study population consisted of 214 healthy adults. Considering the distribution of vitamin B12 levels and accepting 25 % and 75 % percentiles as the cut-off values, the participants were divided into 3 groups. Laboratory, echocardiography and electrocardiography (ECG) measurements were compared between three groups. ECG measurements were performed manually and Tpeak-Tend (Tp-e), Tp-e corrected (Tp-ec), QT and QT corrected (QTc) intervals were calculated. Results: the patients in Group 1 (vitamin B12 < 253 pg/ml) were found to have significantly higher QT and QTc dispersions, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios when compared to those in Group 2 (253 pg/ml < vitamin B12 > 436 pg/ml) and Group 3 (vitamin B12 > 436 pg/ml). On the other hand, a negative significant correlation was detected between vitamin B12 levels and Tp-e, Tp-e/QT, Tp-e/QTc ratios, QT and QTc dispersions. Conclusion: a low level of vitamin B12 in healthy individuals can be a significant indicator of arrhythmogenic susceptibility. A close follow-up of these subjects in terms of arrhythmogenic predisposition can be useful.

Electrocardiographic Predictors of Cognitive Decline and Dementia: A Systematic Review.

Markers of altered cardiac function might predict cognitive decline and dementia. This systematic review aims to review the literature that examines the associations of various electrocardiogram (ECG) markers with cognitive decline and dementia in middle-aged and elderly populations. We searched PubMed, Embase, and Web of Science through 1 July 2020 for literature and conducted a systematic literature review. We included studies examining the associations of ECG markers (e.g., left ventricular hypertrophy [LVH], spatial QRS-T angle, and QT prolongation) with cognitive function and dementia in adult populations regardless of study setting and design, but excluded studies examining atrial fibrillation and heart rate variability. Fourteen community-based cross-sectional and longitudinal studies were identified. ECG markers were investigated in association with dementia in four prospective studies, and with cognitive decline in ten prospective studies. ECG-assessed LVH was associated with dementia in one study while five heterogeneous prospective studies yielded inconsistent associations with cognitive decline. Regarding ventricular repolarization markers, spatial QRS-T angle was associated with cognitive decline in one study while another study found no association between QT prolongation and cognitive decline. High resting heart rate was associated with both dementia and cognitive decline in one study but not associated with dementia in another study. P-wave abnormality was significantly associated with incident dementia and cognitive decline in one prospective study. Some ECG markers were associated with incident dementia and cognitive decline. However, limited number of heterogeneous studies did not allow us to make firm conclusions. Further studies are needed.

Assessment of proarrhythmic ventricular electrophysiological remodeling in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is related to cardiovascular disease and results in increased mortality rates. Ischemia, autonomic nervous system dysfunction, impaired cardiac ionic currents, and genetic predisposition may be the underlying mechanisms. Proarrhythmic ventricular electrophysiological remodeling detected on the basis of Tp‑e interval, Tp-e/QT, and Tp-e/QTc ratios plays akey role in the prognosis. Our aim was to assess proarrhythmic ventricular electrophysiological remodeling in patients with RA, awell-known chronic inflammatory disorder. Atotal of 163patients with RA and 47patients as acontrol group were included in this retrospective study. Proarrhythmic ventricular electrophysiological remodeling markers were evaluated in both groups along with baseline demographic and clinical variables. Patients using medication or with chronic disorders that can affect ventricular repolarization markers were excluded. The patients with RA had prolonged Tp‑e interval (66ms [44-80]; 80ms [78-96], p < 0.001) and increased Tp-e/QT ratio (0.18 [0.12-0.22]; 0.22 [0.20-0.24], p < 0.001) and Tp-e/QTc ratio (0.16 [0.11-0.19]; 0.20 [0.17-0.22], p < 0.001) compared to the control group. The Tp‑e interval and Tp-e/QT ratio, which may help to clarify the pathophysiological mechanisms of ventricular arrhythmias, were increased in patients with RA.

Novel markers of ventricular repolarization are associated with mortality in patients undergoing surgical aortic valve replacement for severe aortic stenosis.

Aortic stenosis (AS) is the most common degenerative valvular heart disease that can affect left ventricular functions. Tp-e interval and Tp-e/QT ratio is a novel repolarization marker which is associated with adverse cardiovascular events in several cardiovascular diseases. In our study, our aim is to investigate the prognostic effect of Tp-e interval, Tp-e/QT and Tp-e/QTc ratios on mortality in patients who underwent successful surgical aortic valve replacement (AVR). A total of three hundred seventy-five patients undergoing successful surgical AVR were included in this study. Then, patients were divided into two groups according to mortality as group 1 without mortality (342 patients) and group 2 with mortality (33 patients). Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were calculated for both groups. Tp-e interval (71 (63.7-77); 86 (84-88), p < .001), Tp-e/QT ratio (0.19 (0.17-0.20); 0.23 (0.22-0.23), p < .001) and Tp-e/QTc ratio (0.17 ± 0.02; 0.21 ± 0.01, p < .001) were higher in group 2 compared to group 1. In multivariate logistic regression analyses Tp-e interval (odds ratio [OR]: 1.315, 95% confidence interval [CI]: 1.203-1.437, p < .001), Tp-e/QT ratio (OR: 7.334, 95% CI: 3.274-1.643, p < .001) and Tp-e/QTc ratio (OR: 2.567, 95% CI: 4.106-1.605, p < .001) were found to be independent predictors of mortality. Additionally, a Kaplan-Meier survival analysis also revealed that long term survival was found to be significantly decreased in patients with higher Tp-e/QT ratio (Log-Rank p < .001) and Tp-e/QTc ratio (Log-Rank p < .001). Tp-e interval, Tp-e dispersion, Tp-e/QT, and Tp-e/QTc ratios are associated with worse prognosis after surgical AVR in patients with severe AS. All of them are also independent predictors of mortality.

B-011-01 TRANS-ANCESTRY GWAS OF 252,730 INDIVIDUALS IDENTIFIES 114 NOVEL LOCI ASSOCIATED WITH THE QT INTERVAL

The QT interval, a marker of ventricular repolarization, is a heritable, independent predictor of risk for ventricular arrhythmias and sudden cardiac death (SCD). Previous genome-wide association studies (GWAS) of the QT interval have highlighted pathways regulating cardiac ion channels, calcium signaling and myocyte internal structure. However, a large proportion of the heritability remains unexplained, suggesting additional mechanisms remain undiscovered. To identify new candidate genes and pathways relevant to ventricular repolarization to elucidate novel mechanisms underlying arrhythmogenesis. We performed the largest trans-ancestry QT GWAS meta-analysis to date, using 35 studies imputed with 1000G / HRC reference panels, comprising a total sample of 252,730 individuals (84% European, 7.7% Hispanic and 6.7% African ancestry/ethnicity). Candidate gene prioritisation and gene-set enrichment analyses were performed using DEPICT. We identified 176 independent loci (114 novel) associated with QT. SNP-based heritability in European ancestry UK-Biobank participants was 29.3%. The variance explained by lead and conditionally independent variants was 14.6%. Across all loci, the top 30 gene-ontology terms highlighted by DEPICT included processes involved in either muscle cell differentiation, tissue development, insulin receptor signaling or regulation of gene expression. At one locus (CD36), the association was driven by studies of African ancestry only. This gene encodes an immune-metabolic receptor necessary for appropriate myocardial substrate utilisation. Another novel locus (FAM9B) was identified in male-stratified X-chromosome analyses. Other candidate genes highlighted include cardiac Z-disk proteins (C10orf71), enzymes with cardioprotective roles in oxidative stress (PON2), cardiomyocyte glucose transporters (GLUT4) and regulators of cell morphology and cytoskeleton organization (BRWD1). Our analyses highlight novel genes and pathways associated with the QT interval that may expose new mechanisms, which contribute to arrhythmogenesis and SCD and could serve as new therapeutic targets.

478 The Relationship between Sleep Disordered Breathing, Markers of Ventricular Repolarization and Cardiovascular Mortality

Abstract Introduction Sleep disordered breathing (SDB) is associated with increased mortality. Obstructive apneas/hypopneas have been associated with an increase in both QTc duration and QT variability. These markers of ventricular repolarization are associated with arrhythmias and death. It is unknown whether SDB-related QTc changes are responsible for the relationship between QTc/QT variability and cardiovascular death (CVD). Methods From the Sleep Heart Health Study, we randomly selected 200 subjects in each of four groups based on overall apnea/hypopnea index: those with no SDB and those in either, mild, moderate or severe SDB at baseline, matched for gender, age and BMI. Respiratory-related channels and electrocardiograms (ECG) from each polysomnography were analyzed. QTc was calculated using Bazett’s heart rate correction. The following measures of QT variability were obtained: i) standard deviation of QT intervals (SDQT) at 1- and 5-minute intervals and ii) short-term interval QT variability (STVQT) at 5-minute intervals. Cox proportional hazards regression models were used to evaluate potential predictors of CVD. Results Twenty-nine subjects were excluded either due to missing data or low quality ECG. The 771 subjects included were 68±10 years of age, half were female. During follow-up, 220 subjects (28.5%) died of CVD among whom, 67 (30.5%) had comorbid severe SDB, 45 (20.5%) had no SDB, and the remaining CVD deaths had mild (47, 21.4%) and moderate 61 (27.7%) SDB. The CVD patients were more likely to be older(p&amp;lt;0.001), hypertensive (p&amp;lt;0.001), diabetic(p&amp;lt;0.001), and had increased SDQT(p&amp;lt;0.001), STVQT(p&amp;lt;0.001) and QTc (0.017). After adjusting for covariates, the presence of mild (p=0.562), moderate(p=0.439) and severe SDB (p=0.912) did not moderate the association between QTc prolongation and CVD. Additionally, mild (p=0.486), moderate(p=0.478) and severe SDB (p=0.849) did not moderate the association between SDQT and CVD. Similarly, mild (p=0.144), moderate(p=0.594) and severe SDB (p=0.508) did not moderate the association between STVQT and CVD. However, QTc, SDQT, STVQT, mild and severe SDB were individually associated with CVD (p=0.004, 0.000, 0.000, 0.014, 0.022, respectively). Conclusion SDB was not a factor in the relationship between QTc prolongation/QT variability and CVD. Support (if any) American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140), University of Arizona Health Sciences Career and Development Award (5299903)

Associations of frontal QRS-T angle with left ventricular volume and function derived from ECG-gated SPECT in patients with advanced chronic kidney disease.

The frontal QRS-T angle is one of markers of ventricular repolarization. We investigated whether or not the frontal QRS-T angle could predict left ventricular (LV) volume and function derived from ECG-gated SPECT in patients with advanced chronic kidney disease (CKD). Two hundred and twelve patients with advanced CKD defined as estimated glomerular filtration rate of < 45ml min-1/1.73 m2 were enrolled. Wide QRS-T angle was defined as its angle of > 90°, and was considered abnormal. Enlarged LV end-diastolic volume (LVEDV) was defined as LVEDV index of > 76ml m-2 in men and > 57ml m-2 in women. Reduced LV ejection fraction (LVEF) was defined as LVEF of < 40%. Fifty-one patients (24%) had wide QRS-T angle, and 161 patients (76%) had normal QRS-T angle. Patients with wide QRS-T angle had larger SSS [9 (5-16) vs 4 (1-9), p < 0.001], larger LVEDV index (69 ± 29 vs 50 ± 18ml m-2, p < 0.001) and lower LVEF (47 ± 13 vs 59 ± 12%, p < 0.001) than those with normal QRS-T angle. Multivariate analysis showed that wide QRS-T angle (odds ratio 5.93; 95% CI 2.55-14.33; p < 0.001) was significantly associated with enlarged LVEDV, whereas SSS severity was not. Severely abnormal SSS (odds ratio 3.80; 95% CI 1.16-14.05; p < 0.03) and wide QRS-T angle (odds ratio 5.67; 95% CI 2.10-16.22; p < 0.001) were significantly associated with reduced LVEF. Our results suggest that wide QRS-T angle is associated with LV remodeling such as enlarged LVEDV or reduced LVEF in patients with advanced CKD.