Bazett's Formula Research Articles

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).

PO49 Presentation Time: 10:00 AM: Prevalence of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy

<h3>Purpose</h3> QTc has been associated not only with a higher risk of Torsade de Pointes (TdP), sudden cardiac arrest but also with general cardiac mortality, including cardiovascular and coronary death. We examined the prevalence of prolonged QTc interval in prostate cancer patients undergoing brachytherapy in general and in patients with more aggressive cancers who may be exposed to ADT and compared them to patients who underwent prostatectomy. <h3>Materials and Methods</h3> We randomly selected 1094 patients treated with either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy between August 2010 and February 2022 from our internal database. All patients had an ECG as part of the preoperative work-up. The QTc was automatically calculated using the Bazett formula. Excluded were patients with left or complete bundle branch block, ventricular extrasystoles, atrial fibrillation, presence of a pacemaker or a QRS ≥ 120 ms. .As primary outcome, a QTc ≥450ms was considered abnormal. Chi-square or Fisher's exact test, when appropriate was used to compare groups. Pearson correlation coefficient and binary multivariable regression analysis was used to evaluate correlations between QTc and clinical values. <h3>Results</h3> A total of 6.2% (n=68) had a QTc ≥450ms. Patients with a Cancer of the Prostate Risk Assessment (CAPRA) high risk disease (score 6-10) were significantly more likely to have a QTc ≥450ms than patients with low-or intermediate risk (9.7% vs. 5.5%, p=0.039). QTc as a continuous variable correlated weakly with the neutrophil count (r=0.13, p<0.001), age (r=0.08, p=0.009) and inversely with testosterone (r=-0.17, p=0.002). On binary multivariable regression analysis including neutrophils, testosterone and age, only testosterone [nmol/L] was predictive of a QTc ≥450ms, OR 0.9, 95% CI 0.82-0.98, p=0.02. We then compared the patients treated with brachytherapy to 178 patients who underwent prostatectomy. The latter had a non-significantly smaller portion of patient with a QTc ≥450ms: 4.5% vs. 6.2%, p=0.5. <h3>Conclusions</h3> Our data show that about 10% of patients with high-risk prostate cancer are at increased risk of TdP. Treating physicians should be aware of this and monitor the QTc during ADT to possible decrease cardiac mortality in these patients who require ADT. The correlation between increasing age, neutrophil count and low testosterone with QTc prolongation links inflammation and hypogonadism.

Anthracycline Chemotherapy-Induced Electro-Mechanical Changes: Strain Echocardiography Combined with Repolarization Parameters on Electrocardiography to Predict Early Cardiotoxicity.

The aim of the study was to describe the acute cardiotoxic effects of anthracycline chemotherapy in echocardiographic strain and electrocardiographic repolarization parameters in patients with breast cancer. A total of 35 consecutive patients (all females, mean age: 48.9 ± 11.8 years) who received chemotherapy due to breast cancer were prospectively included. Pre-treatment (T0) and third month (T2) 2-dimensional strain echocardiography and electrocardiography were performed. Additionally, within 3 hours of the first dose of chemotherapy (T1), additional electrocardiographic images were obtained. All mechanical and electrical parameters from different time intervals (T0, T1, and T2) were compared with each other. In the acute period after treatment, electrocardiographic repolarization parameters were prolonged and this prolongation continued to the third month (QT corrected with Bazett formula [440.10 ± 27.63 (T0), 468.00 ± 38.98 (T1), 467.86 ± 35.09 (T2)], QT dispersion [49.85 ± 19.52 (T0), 69.54 ± 16.06 (T1), 57.63 ± 14.42 (T2)], and T-wave peak-to-end interval [94.00 ± 45.46 (T0), 131.20 ± 17.79 (T1), 120.00 ± 18.32 (T2)]; P &lt; .001). There was no significant change in global longitudinal strain values before and after treatment (global longitudinal strain avg: -21 ± 7.1%; P = .8). However, there were significant reductions in strain parameters including circumferential and radial strain, and torsion (-17.2 ± 3.5 to -13 ± 2.84; P &lt; .001, 45.1 ± 8.3 to 35.6 ± 10; P &lt;.001, and 12.1 ± 3.5 to 7.7 ± 2.1; P &lt; .001, respectively). Both the electrical and mechanical functions of the heart can be impaired acutely extending to 3 months after anthracycline chemotherapy. Therefore, cardiotoxicity should be evaluated early both electrically and mechanically after chemotherapy.

QTc interval in anorexia nervosa: a systematic review and meta-analysis

Abstract Background Patients with anorexia nervosa (AN) are at higher risk of sudden cardiac death. Although the underlying aetiology for this association remains unclear. It may be related to prolongation of the QT interval, which can degenerate into fatal ventricular arrhythmias. However, the presence of prolonged heart rate-corrected QT interval (QTc) in AN remains controversial, and two previous meta-analyses on AN and QTc showed contradictory findings [1,2]. Purpose In this systematic review and meta-analysis, we aimed to evaluate if AN was associated with changes in the QTc interval and dispersion. Methods MEDLINE, EMBASE and COCHRANE databases were systematically searched from inception to January 2021. Random-effects meta-analysis and meta-regression were used. The inclusion criteria were (i) confirmed diagnosis of AN, (ii) measurement of QTc on electrocardiogram and (iii) peer-reviewed articles. The primary endpoint of the study was the duration of the QTc interval calculated using the Bazett (QTcB), Hodges (QTcH), Fridericia (QTcF) and Framingham (QTcFr) formulae. The secondary endpoints were QT dispersion (QTd) and QTc dispersion (QTcd). Results The 25 eligible studies included 5687 patients (1862 AN, 3825 control) (Figure 1: PRISMA diagram). The majority of patients were female (96.3%) with a mean age between 14.3 to 31.0 years and mean duration of disease ranging from 9.1 to 129.6 months. The mean BMI ranged from 13.7 to 18.5 kg/m2. Pooled analysis did not show significant prolongation between AN versus control in QTcB (mean difference (MD) MD 4.9ms, 95% CI −3.2, 13.1ms, p=0.23; I2=95%; n=24/25 studies; Figure 2A), QTcH (MD 1.3ms, 95% CI −8.5, 11.2ms, p=0.79; I2=71%; n=3/25 studies), and QTcF (MD 3.1ms, 95% CI −21.6, 27.7ms, p=0.81; I2=97%; n=3/25 studies). Only two studies reporting QTcFr showed a significant prolongation between AN and control (MD 15.9ms, 95% CI 0.0, 31.8ms, p=0.05, I2=65%; n=2/25 studies; Figure 2B). However, QTd and QTcd were significantly greater in AN than control (MD 21.3ms, 95% CI 10.4, 32.3ms, p=0.0001, I2=94%; Figure 2C and MD 16.9ms, 95% CI 4.5, 29.3ms, p=0.007 I2=93%; Figure 2D, respectively). Conclusion To the best of our knowledge, this is the largest meta-analysis of QTc in AN and the first meta-analysis exploring the significance of QTd and QTcd in AN. AN was not found to be associated with prolongation of QTc calculated using the Bazett, Fridericia and Hodges formulae. However, an association of AN with prolonged QTc was observed in the studies using the Framingham formula. More pronounced dispersion (QTd and QTcd) was also observed in patients with AN. Funding Acknowledgement Type of funding sources: None.

The incidence and clinical features of anticancer therapy induced atrial fibrillation in patients with breast cancer without previously established cardiac disorder

Abstract Background/Introduction Anthracyclines (ATC), alkylating (AAg) and anti-microtubule (AMA) agents are established chemotherapeutics in management of breast cancer. Both agents might reveal cardiotoxicity, as well as cancer treatment–induced-arrhythmias at varying established rates and by complex mechanisms. Atrial fibrillation (AF) is one of the debilitating dysrhythmias encountered throughout the cancer treatment with a significant impact on mortality and morbidity. Purpose To reveal the incidence and clinical features of new onset AF episodes detected in breast cancer patients using different conventional chemotherapeutic regiments. Methods All consecutive adult women diagnosed with breast-carcinoma and getting the first chemotherapy treatment with either ATC+AMA or AAg+AMA were prospectively evaluated for 6 months. Clinical, echocardiographic and ECG parameters (QTc by Bazett's-formula) were obtained and evaluated on baseline, first month and 6th month. Patients with Structural/coronary-heart-disease, complete-bundle-branch-block, non-sinus-rhythms and acute-coronary-syndrome in follow-up were excluded. “AF” is diagnosed on 12-lead-ECG or at least 30s of AF on Rhythm/Holter monitoring indicated by palpitation symptoms. Results Of 192 cases, 140 women ([mean±SD] age, 64±12, [range] 36–86 years) were enrolled for analysis. 76 patients received the AAg (cyclophosphamide) and 64 received ATC (daunorubicin) in addition to AMA (docetaxel). Mean follow up time was 4.2±2 months (Min–Max 1–6 months). Incident AF was diagnosed in 38 patients (27.1%) at the end of the 6 month follow up. The clinical findings are presented in picture-1. In patients receiving ATC treatment, incident AF was significantly more common (35.9% vs 19.7, p=0,032) and mostly observed in the first month of ATC-chemotherapy compared with AAg-regiments respectively (69% vs 33% of AF events occurred in first month, P&amp;lt;0,001). Incident AF patients were significantly older, and ATC-receiving patients demonstrated significantly greater heart-rate and PR-interval changes from baseline. Age, ATC use, Delta-PR &amp;gt;10 ms, Delta-QTC &amp;gt;50 ms and Delta HR &amp;gt;10 ms from baseline significantly predicted incident AF in the 6 month follow up in univariate-regression-analysis. However, only age and more significantly Anthracyclin use was found to predict Incident AF in multivariate regression analyses (picture 2) [(OR 3.7 (95% CI 1.2–10) (p=0.02)]. Conclusion(s) Compared with alkylating-agents, anthracycline-regimens seem to induce significantly more incident-AF-events and profound ECG changes on the acute phase of chemotherapy for breast-cancer in women. They seem to exert their effects irrespective of conventional AF risk-factors apart from advanced-age. Affected ECG-parameters of delayed-conduction and repolarization-heterogeneity might be suggested as a surrogate for multiple-ion-channel-interactions and a possible mechanism underlying higher incident-AF. Funding Acknowledgement Type of funding sources: None.

Association of QTc Formula With the Clinical Management of Patients With Cancer

Monitoring of the corrected QT interval (QTc) for patients with cancer receiving chemotherapy is not standardized. Selection of QTc formula may be associated with adverse event grading and chemotherapy delivery. To describe the association of QTc formula selection with adverse event grading and chemotherapy delivery. This retrospective observational cohort study used data from January 2010 to April 2020 and included adult patients seen at the University of North Carolina Cancer Hospital who had an electrocardiogram (ECG) performed. Adjusted QTc using the Bazett, Fridericia, and Framingham formulae. The main outcome was QTc prolongation using the Common Terminology Criteria for Adverse Events (CTCAE). Consistency between formulae was evaluated. Subsequently, appropriateness of clinical management due to prolonged QTc was assessed for a subset of patients being treated with chemotherapy agents associated with a prolonged QT interval. We hypothesized that use of the Bazett formula would be associated with higher rates of QTc prolongation and inappropriate modifications to chemotherapy. A total of 19 955 ECGs from 6881 adult patients (3055 [44.4%] women, 3826 [55.6%] men; median [IQR] age at first ECG, 60 [47-68] years) were analyzed. The percentage of ECGs with grade 3 QTc prolongation differed by formula (all patients: Framingham, 1.8%; Fridericia, 2.8%; and Bazett, 9.0%; patients receiving QT-prolonging chemotherapy [2340 ECGs]: Framingham, 2.7%; Fridericia, 4.5%; and Bazett, 12.5%). The Bazett formula resulted in a median QTc value 26.4 milliseconds higher than Fridericia and 27.8 milliseconds higher than Framingham. Of the 1786 ECGs classified as grade 3 by Bazett, 1446 (81.0%) were grade 2 or less by either Fridericia or Framingham. A total of 5 of 28 (17.9%) evaluated clinical changes associated with prolonged QTc were deemed inappropriate when using either Fridericia or Framingham formula. Findings of this cohort study suggest that the Bazett formula resulted in higher QTc values associated with a 3-fold increase in grade 3 CTCAE toxic effects compared with other common formulae. Use of the Bazett formula likely was associated with inappropriate changes in clinical management. These data support the use of a standard QTc formula (such as Fridericia or Framingham) for QTc correction in oncology.

Importance of Formula-Specific Centile Thresholds for Evaluation of Heart Rate-Corrected QT Prolongation in Williams Syndrome

Patients with Williams syndrome (WS) have a 25- to 100-fold higher risk of sudden death and prolonged heart rate-corrected QT (QTc). A recent study using the Fridericia formula for QT correction suggested that prolongation is principally an issue of heart rate. We used multiple published heart rate correction formulas to reevaluate the prevalence of QTc prolongation in our original dataset from our 2010 study at the Children's Hospital of Philadelphia. The ninety-eighth centile for QTc and corrected JT Interval (JTc) of the control population for each formula were used to set the threshold for prolongation. Prevalence comparison was done with Fisher's exact test. Predictors of longer QTc/JTc were assessed using linear regression models adjusting for age, gender, and heart rate. Adjusted odds of QTc/JTc prolongation were evaluated with conditional logistic regression models matched based on age and heart rate. There were 482 electrocardiograms from 188 patients with WS and 1,522 from normal controls. Patients with WS were younger, with higher heart rates and shorter RR and QRS intervals. WS was associated with longer QTc/JTc compared with controls. There were higher odds of prolonged QTc/JTc in patients with WS than controls using both Bazett and Fridericia formulas. In conclusion, this study confirms the higher prevalence of QTc prolongation in WS compared with controls and highlights the importance of setting appropriate formula-specific upper thresholds for QTc prolongation for accurate diagnosis.

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

Electrocardiographic changes associated with SGLT2 inhibitors and non-SGLT2 inhibitors: A multi-center retrospective study.

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors has been shown with cardiovascular benefit in type 2 diabetes mellitus (T2DM) patients. However, its osmotic diuresis still concern physicians who may look for possible electrolyte imbalance. We therefore aimed to investigate electrocardiographic (ECG) changes associated with SGLT2 inhibitors.MethodsElectronic medical records from Chang Gung Research Database between January 1, 2001 and January 31, 2019 were searched for patients with ECG reports and patients on an oral hypoglycemic agent (OHA). We then separate these T2DM patients with EKG into those taking either SGLT2 inhibitors or non-SGLT2 inhibitors. We excluded patients with OHA use <28 days, age <18 years, baseline ECG QTc > 500 ms, and ECG showing atrial fibrillation or atrial flutter. Propensity score matching (PSM) was performed between groups by age, sex, comorbidities, and medications (including QT prolonging medications). Conditional logistic regression and Firth's logistic regression for rare events were employed to compare the difference between SGLT2 and non-SGLT2 inhibitor patients.ResultsAfter exclusion criteria and PSM, there remained 1,056 patients with ECG on SGLT2 inhibitors and 2,119 patients with ECG on non-SGLT2 inhibitors in the study. There were no differences in PR intervals, QT prolongations by Bazett's or Fridericia's formulas, new onset ST-T changes, new onset CRBBB or CLBBB, and ventricular arrhythmia between the group of patients on SGLT2 inhibitors and the group of patients on non-SGLT2 inhibitors. There were no differences between the two groups in terms of cardiovascular death and sudden cardiac death. In addition, there were no differences between the two groups in terms of electrolytes.ConclusionsCompared with T2DM patients on non-SGLT2 inhibitors, there were no differences in PR interval, QT interval, ST-T changes, bundle-branch block, or ventricular arrhythmia in the patients on SGLT2 inhibitors. There were no differences in cardiovascular mortality between these two groups. In addition, there were no electrolyte differences between groups. SGLT2 inhibitors appeared to be well-tolerated in terms of cardiovascular safety.

Systemic primary carnitine deficiency induces severe arrhythmias due to shortening of the QT interval

Systemic primary carnitine deficiency is a rare genetic disease characterized by severe hypokinetic dilated cardiomyopathy and/or severe rhythm disorders. Without carnitine supplementation, evolution is usually towards a fatal cardiac decompensation. While the cardiomyopathy is most likely secondary to the energy deficiency, the mechanism of the rhythm disturbance is unclear, and may be related to a significant shortening of the QT interval. The aim of this work was to describe rhythmic manifestations at the diagnosis of primary carnitine deficiency and their evolution with carnitine supplementation. We conducted a retrospective multicenter study, including all French patients with a confirmed diagnosis of primary carnitine deficiency. Clinical and paraclinical data at diagnosis and during follow-up were collected. QT interval were measured by two pediatric cardiologists according to international recommendations and corrected with the Bazett formula (QTc). Nineteen patients (median age at diagnosis 2.3 years) followed in 8 French centers were included. At diagnosis, 22% of the patients (4/18) had arrhythmia (1 sudden death, 1 ventricular tachycardia and 2 ventricular fibrillations), and 78% (14/18) had a cardiomyopathy. Seven electrocardiograms before initiation of treatment out of the 9 available displayed a QTc < 340 ms indicating the diagnosis of short QT. The mean QTc after carnitine supplementation was 385 ± 24 ms versus 334 ± 21 ms before treatment ( P < 0.01). No patient reached the criteria of short QT syndrome with carnitine supplementation. Three patients died during the survey, which included one sudden death before carnitine supplementation, one non-recoverable rhythmic storm also before initiation of supplementation, and one sudden death in a patient who stopped carnitine supplementation 16 years after diagnosis. Primary carnitine deficiency is associated with a short QT interval that induces severe arrhythmias and sudden death. Carnitine supplementation normalizes the QTc and avoids arrhythmias. The screening of primary carnitine deficiency in neonates would prevent neonatal death.

Anesthesia induction regimens may affect QT interval in cardiac surgery patients: A randomized-controlled trial.

Background The aim of this study was to investigate the effects on QT interval of the propofol-ketamine combination and the midazolam-fentanyl combination in anesthesia induction for cardiac surgery. Methods Between September 2020 and June 2021, a total of 9 5 c ardiac s urgery p atients ( 80 m ales, 1 5 f emales; mean age: 57±9.1 years; range, 26 to 76 years) were included. The patients were divided into two groups as Group PK (propofol-ketamine, n=50) and Group MF (midazolam-fentanyl, n=45). The 12-lead electrocardiographic and hemodynamic measurements were performed at three time points: before anesthesia induction, after anesthesia induction, and after endotracheal intubation. The measurements were evaluated with conventional Bazett's formula and a new model called index of cardio-electrophysiological balance. Results The evaluated QTc values of 95 patients after anesthesia induction were significantly prolonged with the Bazett's formula and the index of cardio-electrophysiological balance in Group PK (p=0.034 and p=0.003, respectively). A statistically significant QTc prolongation was observed with the index of cardio-electrophysiological balance after laryngoscopy and endotracheal intubation in Group PK (p=0.042). Hemodynamic parameters were also higher in Group PK. Conclusion Our study shows that the propofol-ketamine combination prolongs the QTc value determined by the Bazett's formula and the index of cardio-electrophysiological balance model. Using both QTc measurement models, the midazolam-fentanyl combination has no prolongation effect on QTc interval in coronary surgery patients.

C-reactive Protein Elevation Is Associated With QTc Interval Prolongation in Patients Hospitalized With COVID-19.

BackgroundThe relationship between inflammation and corrected QT (QTc) interval prolongation is currently not well defined in patients with COVID-19.ObjectiveThis study aimed to assess the effect of marked interval changes in the inflammatory marker C-reactive protein (CRP) on QTc interval in patients hospitalized with COVID-19.MethodsIn this retrospective cohort study of hospitalized adult patients admitted with COVID-19 infection, we identified 85 patients who had markedly elevated CRP levels and serial measurements of an ECG and CRP during the same admission. We compared mean QTc interval duration, and other clinical and ECG characteristics between times when CRP values were high and low. We performed mixed-effects linear regression analysis to identify associations between CRP levels and QTc interval in univariable and adjusted models.ResultsMean age was 58 ± 16 years, of which 39% were women, 41% were Black, and 25% were White. On average, the QTc interval calculated via the Bazett formula was 15 ms higher when the CRP values were “high” vs. “low” [447 ms (IQR 427–472 ms) and 432 ms (IQR 412–452 ms), respectively]. A 100 mg/L increase in CRP was associated with a 1.5 ms increase in QTc interval [β coefficient 0.15, 95% CI (0.06–0.24). In a fully adjusted model for sociodemographic, ECG, and clinical factors, the association remained significant (β coefficient 0.14, 95% CI 0.05–0.23).ConclusionAn interval QTc interval prolongation is observed with a marked elevation in CRP levels in patients with COVID-19.

QT Interval Prolongation Is a Novel Predictor of 1-Year Mortality in Patients With COVID-19 Infection.

BackgroundQT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known.PurposeTo evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection.Materials and MethodsA total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk.ResultsOne-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3–3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22–3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06–2.68, p = 0.027).ConclusionProlonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.

QT interval prolongation is a novel predictor of one year morality in patients with coronavirus disease-19 infection

Funding AcknowledgementsType of funding sources: None.BackgroundQT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known.PurposeTo evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection.MethodsA total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 hours from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥440 msec in males and ≥450 msec in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk.ResultsOne-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70±14.4 vs 62.7±16.6, p <0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5; p=0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.7% vs 16.9; p <0.001, adjusted HR 1.85[1.2-2.84]; p=0.005). Compared to patient without QTc prolongation and no myocardial injury, the adjusted 1-year mortality risk was highest in patients with prolonged QTc and myocardial injury (HR 6.63, 95% CI 2.28-19.3; p=0.001), followed by patients with QTc prolongation without myocardial injury (HR 6.12 95% CI 1.83-20.49; p=0.003), and patients with myocardial injury without QTc prolongation (HR 4.95 95% CI 1.83-20.49.; p=0.003).ConclusionProlonged QTc is an independent risk factor for both myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.

P171 EVALUATION OF ARRHYTHMIC RISK IN THE PSYCHOPHARMACOLOGIC–TREATED PATIENT

Abstract Background Neuroleptics (NRL) and Tricyclic Antidepressants (TCA) could be related to the QT prolongation although the risk of ventricular arrhythmias and sudden death caused by these drugs was not clearly described in literature. Corrected QT (QTc), is the major marker of arrhythmic risk; Qt dispersion (QTd) is defined as the dispersion of the QT interval on 12–lead electrocardiogram (ECG) and is predictive of mortality if &amp;gt; 58; the heart rate variability (HRV) is indicative of the sympathetic/vagal tone and of the arrhythmic risk. Aim of the study. Evaluation of the main effects of psychotropic drugs in psychiatric patients on the following parameters: QT interval, QTc using 4 formulas (Bazett, Fridericia, Framingham e Hodges), Qtd and HRV depending on time and heart rate. Materials and Methods Data from 167 patients treated with typical and atypical NRL, TCA, and mood stabilizers have been collected. The observational study consisted in these phases: 1) chart review of 84 patients admitted in day hospital to detect sex, age, diagnosis, therapy and Qtc; 2) evaluation of the same parameters in 83 of them, to whom an ECG was performed at the discharge; 3) ECG Holter in a subgroup of 17 patients who have given consent to the exam, to highlith the incidence of arrhythmias and to investigate the HRV. Results No significant QTc alterations related to therapy were detected at the admission or at the discharge. Moreover, no statistically significant differences emerged among NRL classes nor an increased arrhythmic risk in polypharmacy. The use of different formulas has confirmed an overestimation of the QTc according to the Bazett formula. QTd was altered in 67 patients ( QTd ≥50 in 51 subjects; QTd&amp;gt;60 in 12 subjects)and the HRV was lower compared to the general population regardless of the therapies. Conclusions The psychopharmacological therapy in a “real world setting” didn’t show a signiticative influence on the evaluated parameters of arrhythmic risk. The arrhythmic risk is low in absence of other risk factors or comorbidities. QT correction using FRI or HOD, the QTd if QTc &amp;gt;450–470 ms and the HRV in patients with arrhythmic risk factors, should be considered as parameters to evaluate in the clinic routine of follow–up of psychopharmacologic–treated patient.

Assessment of the QT interval in right bundle branch block

Background Identifying prolonged QT interval in RBBB has been problematic. Methods Four approaches were compared to adjust for the QT prolongation in intermittent RBBB. The implications were assessed in a separate group of 200 persons with established RBBB. Results In 12 individuals, mean age 74.5 years with intermittent RBBB, the presence of RBBB significantly (p < 0.05) increased the QT interval in each of six different heart rate correction formulae by an amount ranging from 35.4 ms in the Hodges formula to 50.2 ms in the Bazett formula. Four different equations were tested to adjust the QT interval and one approach QTcRBBB = 0.945*QTcRBBB − 26 was the best method to adjust for the increased QT in RBBB as it produced a QT value that was not significantly different from the QT interval in the absence of RBBB in intermittent RBBB. Failure to adjust the QT interval in RBBB produces an overestimate of the QT interval which in some heart rate adjustment formulae was marked. For the Bazett heart rate adjustment approach QTc 450 ms was found in 73.9% of men and QTc over 460 ms was found in 60.6% of women. Conclusion These data suggest the implementation of a new approach to recalculate the QT intervals in RBBB. QTcRBBB = 0.945*QTcRBBB − 26 with an appropriate heart rate adjustment formula (other than the Bazett formula) accurately predicts the QT interval in the absence of RBBB.

Association of QTc Interval and V4-S Wave With Appropriate ICD Therapy in Hypertrophic Cardiomyopathy.

BackgroundVentricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) may lead to sudden cardiac death (SCD). We aimed to investigate the relationship between electrocardiogram (ECG) indicators and the risk of appropriate implantable cardioverter-defibrillator (ICD) therapy in HCM.MethodsThe HCM patients receiving ICD implantation were enrolled consecutively. QT interval correction (QTc) was calculated using Bazett's formula. Long or deep S wave in V4 lead was defined as duration time >50 ms and/or voltage amplitude >0.6 mV. The endpoint in our study was at least one ICD appropriate therapy triggered by ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF), including anti-tachyarrhythmia pacing (ATP) and electrical shock.ResultsA total of 149 patients with HCM (mean age 53 ± 14 years, male 69.8%) were studied. Appropriate ICD therapies occurred in 47 patients (31.5%) during a median follow-up of 2.9 years. Cox regression analysis showed that long or deep S wave in V4 lead [hazard ratio (HR) 1.955, 95% confidence interval (CI) 1.017–3.759, P = 0.045] and QTc interval (HR 1.014, 95% CI 1.008–1.021, P < 0.001) were independent risk factors for appropriate ICD therapy. The ROC showed that the optimal cut-off point value for the QTc interval to predict the appropriate ICD therapy was 464 ms, and the AUC was 0.658 (95% CI 0.544–0.762, P = 0.002). The AUC for S wave anomalies in V4 lead was 0.608 (95% CI 0.511–0.706, P = 0.034). We developed a new model that combined the QTc interval and S wave anomalies in V4 lead based on four patient groups. Patients with QTc ≥464 ms and long or deep V4-S wave had the highest risk of developing appropriate ICD therapy (log-rank P < 0.0001). After adding QTc interval and V4-S wave anomalies into the HCM-risk-SCD model, the prediction effect of the new model was significantly improved, and the NRI was 0.302.ConclusionsIn this HCM cohort, QTc and S wave anomalies in V4 lead were found to be significant and strong predictors of the risk of appropriate ICD therapy. Patients with QTc ≥464 ms and long or deep S wave had the highest risk. After QTc interval and V4-S wave anomalies adding to the HCM-risk-SCD model, the prediction effect is significantly improved.

Association between indices of cardiac repolarization, adiposity and metabolic syndrome. The Polish Norwegian Study (PONS)

BackgroundSeveral cardiac repolarization indices have been associated with cardiovascular disease (CVD) mortality and arrhythmia risk, but little is known about their relation to adiposity in apparently healthy individuals.Study objectiveTo compare prevalence of T‐wave inversion (TWI) and QT interval duration across levels of adiposity and metabolic health.HypothesisWe hypothesized that repolarization indices are associated with body mass index (BMI), waist circumference (WC), waist‐to‐hip ratio (WHR) and metabolic syndrome.MethodsCross‐sectional data of 10531 CVD‐free participants, age 45‐64 years. TWI was considered relevant if present in leads other than V1‐V3, on a standard 12‐lead resting ECG read by study cardiologists. QT intervals were digitally obtained by automated ECG software and were corrected for frequency (QTc, Bazett formula). Metabolic syndrome was defined according to the International Diabetes Federation criteria. We defined metabolically healthy/unhealthy normal weight (MHNW/MUHNW), metabolically healthy/unhealthy overweight (MHOW/MUHOW) and metabolically healthy/unhealthy obesity (MHO/MUO). We used logistic regression and general linear models to adjust for traditional cardiovascular risk factors and beta blockers medication.ResultsIn the overall study population (mean age [SD] 55.2 [5.3] years, 66.4% women), TWI prevalence was 2.59% and ranged from 1.4%, 2.5% to 3.9% in those with normal BMI, overweight and obesity, respectively. There was linear relation between TWI prevalence and BMI decile (p for trend &lt;0.001). Overweight and/or obesity were associated with a 1.47 (95% CI 1.02‐2.12) and 2.09 (95% CI 1.41‐3.08) higher odds of TWI respectively, after multivariable adjustment including left ventricular hypertrophy (Cornell criteria). TWI prevalence was higher for sex‐specific increased vs. normal WHR (3.16% vs. 1.78%) and WC (3.67% vs 1.90%) respectively; these increases persisted after multivariable adjustment. TWI prevalence increased from 2.12% to 3.64% in the presence of metabolic syndrome, but not statistically significant after accounting for BMI. Compared to MHNW, higher adjusted odds (OR, 95%CI) for TWI were observed for those with MHOW (1.52, 1.03‐2.24), MUHOW (1.72, 1.08‐2.77), MHO (1.98, 1.24‐3.16) and MUHO (2.78, 1.87‐4.14). QTc increased from 423.31 to 425.97 ms in the presence of sex‐specific increased WC (delta 2.67 ms, 95% CI 0.82‐4.52), but there were no statistically significant associations with BMI or metabolic syndrome after multivariable adjustments.ConclusionTWI prevalence showed a gradient with BMI and was associated with regional adiposity. Even traditionally considered metabolically healthy overweight/obesity were associated with increased TWI prevalence suggesting early repolarization abnormalities with weight gain. Potential implications: health promotion efforts in conjunction with a simple routine ECG may aid identification of individuals requiring targeted aggressive prevention interventions.

QTc prolongation in adolescents with acute alcohol intoxication

In adults, alcohol intoxication is associated with prolongation of the QT interval corrected for heart rate (QTc). The QTc is influenced by age and sex. Although alcohol intoxication is increasingly common in adolescents, there are no data on the prevalence of QTc prolongation in adolescents with alcohol intoxication. This study aimed to determine the prevalence of QTc prolongation in adolescents with alcohol intoxication and identify at-risk adolescents. In this observational study including adolescents aged 10–18 years, heart rate and QT interval were automatically assessed from an electrocardiogram (ECG) at alcohol intoxication using a validated algorithm. The QTc was calculated using both the Bazett formula (QTcB) and Fridericia formula (QTcF). If present, an ECG recorded within 1 year of the date of admission to the emergency department was obtained as a reference ECG. A total of 317 adolescents were included; 13.3% had a QTcB and 7.9% a QTcF longer than the sex- and age-specific 95th-percentile. None of the adolescents had a QTcB or QTcF > 500 ms, but 11.8% of the adolescents with a reference ECG had a QTcB prolongation of > 60 ms, while no adolescents had a QTcF prolongation of > 60 ms. QTc prolongation was mainly attributable to an increase in heart rate rather than QT prolongation, which underlies the differences between QTcB and QTcF. Male sex and hypokalaemia increased the likelihood of QTc prolongation.Conclusion: QTc prolongation was seen in approximately 10% of the adolescents presenting with alcohol intoxication, and although no ventricular arrhythmias were observed in this cohort, QTc prolongation increases the potential for malignant QT-related arrhythmias. Clinicians must be aware of the possibility of QTc prolongation during alcohol intoxication and make an effort to obtain an ECG at presentation, measure the QT interval, and give an adequate assessment of the findings. We advocate admitting adolescents with alcohol intoxication and QTc prolongation. During hospital admission, we recommend limiting exposure to QTc-prolonging medication, increasing potassium levels to a high-normal range (4.5–5.0 mmol/L) and obtaining a reference ECG at discharge.What is Known:• One out of five deaths in adolescents is alcohol-related. Alcohol intoxication has been related to cardiac arrhythmias and sudden cardiac death.•In adults, alcohol intoxication is associated with QTc prolongation.What is New:•Approximately 10% of the adolescents with alcohol intoxication had a QTc longer than the age- and sexspecific cut-off. In contrast to adults, in adolescents with alcohol intoxication, QTc prolongation is attributable to an increase in heart rate, rather than a prolongation of the QT interval.•Especially males and adolescents with hypokalaemia are at risk of QTc prolongation.

Frequency of QTc Interval Prolongation in Children and Adults with Williams Syndrome.

QTc prolongation (≥ 460ms), according to Bazett formula (QTcB), has been identified to be increased in Williams syndrome (WS) and suggested as a potential cause of increased risk of sudden cardiac death. The Bazett formula tends to overestimate QTc in higher heart rates. We performed a retrospective chart review of WS patients with ≥ 1 electrocardiogram (EKG) with sinus rhythm, no evidence of bundle branch blocks, and measurable intervals. A total of 280 EKGs from 147 patients with WS were analyzed and 123 EKGs from 123 controls. The QTc was calculated using Bazett formula. The average QTcB for individuals with WS and controls was 444 ± 24ms and 417 ± 26ms, respectively (p < 0.001). In our WS cohort 34.4% had at least 1 EKG with a QTcB ≥ 460ms. The mean heart rate (HR) from patients with WS was significantly higher than controls (96bpm vs 76bpm, p < 0.001). Linear regression showed that HR contributed 27% to QTcB prolongation in the patients with WS. Patients with WS have a mean QTcB in the normal range but higher than controls, and a higher than expected frequency of QTc ≥ 460ms compared to the general population. HR is also higher in WS and contributes modestly to the WS QTcB prolongation. Future studies are needed to assess if these findings contribute risk to sudden cardiac death but in the interim we recommend routine EKG testing, especially when starting QTc prolonging medications.