A Study of Tpeak-Tend/QT Interval Ratio in Predicting Heart Failure in ST-Elevation Myocardial Infarction and Its Correlation With N-terminal Pro B-type Natriuretic Peptide (NT-proBNP).

Background Acute ST-elevation myocardial infarction (STEMI) is the most common cause of mortality across the world. The electrocardiogram (ECG) Tpeak-Tend/QT interval appears to be a measure of the left ventricle's transmural dispersion of repolarization (TDR). Prolongation of this time could indicate adverse cardiac events like heart failure, arrhythmias, etc. Heart failure is a clinical syndrome that includes signs and symptoms such as peripheral edema and high jugular vein pressure. N-terminal pro B-type natriuretic peptide (NT-proBNP) is an effective predictor of left ventricular function and also helps in predicting the disease prognosis. Elevated levels of NT-proBNP are seen in many cases of left ventricular dysfunction. This study aims to evaluate the predictive utility of the Tpeak-Tend/QT interval ratio in predicting major adverse cardiac events (MACEs), such as heart failure, by examining the Tend/QT interval ratio values with NT-proBNP in STEMI. Methodology This cross-sectional study was conducted at a tertiary hospital between April 2024 and June 2024. It included STEMI patients, excluding those with non-STEMI (NSTEMI), valvular heart diseases, bundle branch block, or pacemakers. The patients with a Tpeak-Tend/QT ratio < 0.3 were included in group A, and the Tpeak-Tend/QT ratio > 0.3 in group B. They were monitored for MACE-like heart failure during hospitalization and were compared with a study of the Tpeak-Tend/QT interval ratio in predicting heart failure in STEMI and its correlation with NT-proBNP levels. Results In this study, out of 45 patients, male predominance was observed, with 35 (78%) being men and 10 (22%) being women. In group A, the most common age group was 60-70 years, with 16 (51%) patients; in Group B, it was 50-60 years, with six (42.8%) patients. Out of 31 patients in group A, 25 were male, and six were female. In group B, out of 14 patients, 10 were male, and four were female. In this study, out of the 45 patients included, 12 (85%) among 14 patients who had MACEs like heart failure had a Tpeak-Tend/QT interval ratio of more than 0.3, and their measured NT-proBNP levels were also more than 900 pg/mL, thus showing a statistically significant association between Tpeak-Tend/QT interval ratio and NT-proBNP. Conclusion The present study showed an increased Tpeak-Tend/QT interval ratio and NT-proBNP in patients who developed heart failure in STEMI. As ECG is a readily available and affordable tool, the Tpeak-Tend/QT interval ratio can be used along with conventional markers like NT-proBNP to predict MACE in patients with STEMI.

A change in QT interval and ST-segment after radiofrequency catheter ablation in pediatric patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Few studies have examined QT, JT interval, and ST-segment changes due to radiofrequency catheter ablation (RFA) in manifest Wolff-Parkinson-White (WPW) syndrome in pediatric patients. METHODS: The study involved 27 patients (male-to-female, 13:14; age, 12 (5-16) years) who were diagnosed with WPW syndrome and underwent RFA in our hospital between 2009 and 2022. Electrocardiographic (ECG) changes were compared between the group with ventricular preexcitation due to an accessory pathway (manifest group, n = 16) and those without it (concealed group, n = 11). RESULTS: The QT interval before RFA was significantly longer in the manifest group than in the concealed group (402 [362-482] vs. 344 [323-427]; p = 0.001). The QT interval was significantly shortened in the manifest group before and after RFA (402 [362-482] vs. 360 [298-422] msec; p = 0.01). At 1 month, the QT interval difference between the manifest and concealed groups disappeared (366 [305-437] vs. 335 [301-436] msec; p = 0.001). ST-segment changes were found after RFA in 56 % (9/16) of the patients in the manifest group but not in the concealed group. ECG changes presenting the Brugada-pattern was found in one patient. One month later, ECG abnormalities persisted in only one patient. CONCLUSIONS: In pediatric patients, the QT interval was prolonged in manifest WPW syndrome but shortened after RFA. In the manifest group, transient ST-segment change and T-wave abnormalities were often observed after RFA; however, the ECG normalized in approximately 1 month.

Opportunities and challenges for identifying undiagnosed Rare Disease patients through analysis of primary care records: long QT syndrome as a test case.

BACKGROUND: Patients with rare genetic diseases frequently experience significant diagnostic delays. Routinely collected data in the electronic health record (EHR) may be used to help identify patients at risk of undiagnosed conditions. Long QT syndrome (LQTS) is a rare inherited cardiac condition associated with significant morbidity and premature mortality. In this study, we examine LQTS as an exemplar disease to assess if clinical features recorded in the primary care EHR can be used to develop and validate a predictive model to aid earlier detection. METHODS: 1495 patients with an LQTS diagnostic code and 7475 propensity-score matched controls were identified from 10.5 million patients' electronic primary care records in the UK's Clinical Practice Research Datalink (CPRD). Associated clinical features recorded before diagnosis (with p < 0.05) were incorporated into a multivariable logistic regression model, the final model was determined by backwards regression and validated by bootstrapping to determine model optimism. RESULTS: The mean age at LQTS diagnosis was 58.4 (SD 19.41). 18 features were included in the final model. Discriminative accuracy, assessed by area under the curve (AUC), was 0.74, (95% CI 0.73, 0.75) (optimism 6%). Features occurring at significantly greater frequency before diagnosis included: epilepsy, palpitations, syncope, collapse, mitral valve disease and irritable bowel syndrome. CONCLUSION: This study demonstrates the potential to develop primary care prediction models for rare conditions, like LQTS, in routine primary care records and highlights key considerations including disease suitability, finding an appropriate linked dataset, the need for accurate case ascertainment and utilising an approach to modelling suitable for rare events.

Torsades de Pointes electrical storm in children with KCNH2 mutations.

Congenital long QT syndrome (LQTS) is a genetic heart disorder, which may lead to life-threatening arrhythmias, especially in children. Here, we reported two children who were initially misdiagnosed with epilepsy and experienced Torsades de Pointes (TdP) cardiac electrical storm (ES). Through whole exome sequencing (WES), we identified two Potassium voltage-gated channel subfamily H member 2 (KCHN2) mutations (c.1841 C > T and c.1838 C > T) respectively in a 6-year-old boy and a 13-year-old girl. Clinical data indicated that the QT interval was significantly prolonged, the T-wave pattern of chest V5-V6 leads and limb leads were inverted. Our study suggests that patients with epilepsy, especially those refractory epilepsy with atypical features, need comprehensive evaluation of cardiovascular function. KCNH2 mutation in pore region, QT interval prolongation and T wave inversion are high risk factors for ES. For LQT2 patients with ES, Nadolol and left cardiac sympathetic denervation are indicated, sometimes with an ICD.

Uncovering possible silent acquired long QT syndrome using exercise stress testing in long-term pediatric acute lymphoblastic leukemia survivors.

An example of chemotherapy-induced cardiotoxicity in cancer survivors is acquired long QT syndrome (aLQTS), which may cause serious yet preventable life-threatening consequences. Our objective was to identify and characterize childhood acute lymphoblastic leukemia (ALL) survivors with possible aLQTS using maximal exercise testing. In this cross-sectional study with exploratory analysis, a total of 250 childhood ALL survivors were evaluated for abnormal QT interval prolongation using the McMaster cycle exercise test. A total of 198 survivors (102 males; 96 females), having reached their V ̇ O 2 $$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ peak (mean 32.1 ± 8.4 mL/kg/min; range 15.5-57.8 mL/kg/min), were included in our analyses. Two survivors were excluded for possible congenital LQTS. QT intervals were corrected for heart rate using the Bazett, Fridericia, and Rautaharju formulas at rest (supine, sitting, and standing positions), at the end of each stage of the CPET, and at 1, 3, and 5 minutes into the recovery period. The corrected QT (QTc) of borderline (n = 37) and long QT survivors (n = 20) was significantly longer than normal survivors (n = 141) at rest, exercise, and recovery. Out of 57 survivors presenting an abnormal QTc prolongation, 40 survivors (70%) showed no QT interval anomalies at rest but developed various anomalies during exercise. No significant differences were found between the groups for any of the measured clinical characteristics or cardiac parameters. The standardization of exercise testing in the regular follow-up of oncology patients is necessary for appropriate cardiac prevention and surveillance to enhance the health and quality of life of the ever-increasing number of cancer survivors.

Recurrent ventricular arrhythmias and heart failure induced by osimertinib- a case report.

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib. Case summary: A 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655 ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17 ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490 ms and LVEF of 42% after a 6-month follow up. Conclusion: Regular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.

Relevance of accurate QT correction in the assessment of long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a genetic cardiac disease, where the corrected QT (QTc) interval is prolonged. It can cause arrhythmias and lead to a sudden cardiac death. Duration of the QT interval depends on the heart rate and this dependency is treated with QT correction. However, the current QT correction methods have well known problems and limitations. OBJECTIVE: We study the relevance of QT correction method in evaluating the risk of LQTS. We evaluate the reliability of the present and recently developed QT correction methods to discriminate LQTS subjects from healthy controls. METHODS: We use the clinically prevalent QT correction methods, particularly Bazett and Fridericia, in comparison with the recently developed AccuQT method. The data of healthy controls and LQTS subjects is extracted from the Rochester THEW database. The analysis accounts for sex, major LQTS subtypes, and beta-blocker treatment. RESULTS: QT values corrected with AccuQT discriminate the healthy and LQTS samples with the best accuracy, leading to (TP, TN) = (0.87, 0.65) with the conventional 450 ms threshold for LQTS. Fridericia correction yields lower sensitivity (0.71), but comparable balanced accuracy, whereas Bazett shows significantly less accurate results due to overcorrection at lower heart rates. CONCLUSION: The selected QT correction method is important in the identification of LQTS. In particular, the use of Bazett correction should be questioned. Fridericia correction yields good results with respect to its simplicity. AccuQT has the best accuracy out of all the methods for LQTS discrimination. For practical applicability, however, AccuQT needs further validation in realistic clinical conditions.

QT Prolongation Preceding Ventricular Fibrillation After Amiodarone Administration: A Case Report.

Atrial fibrillation (AF) is the most common long-term arrhythmia in adults. Rhythm control in patients with AF involves efforts to restore and maintain sinus rhythm and is accomplished by medication, catheter ablation, or electrical cardioversion. Amiodarone represents one of the most commonly used antiarrhythmic medications. Prolonged use of amiodarone can lead to many side effects. One of the most severe side effects is drug-induced long QT syndrome (LQTS), which can cause malignant arrhythmias and sudden cardiac death. We presented a case of a 52-year-old male who was admitted to the Coronary Unit due to first diagnosed AF with a rapid ventricular response. After amiodarone infusion was administrated the patient lost consciousness and the monitor displayed torsades de pointes (TdP) ventricular tachycardia with rapid conversion to ventricular fibrillation (VF). Cardiac resuscitation with two direct current (DC) shocks was performed. The patient was stabilized, and restoration of sinus rhythm with significant QT prolongation on the ECG was noted. This is a rare case of short-term amiodarone administration causing LQTS, TdP, and VF. The findings or observations emphasize the significance of diligent ECG monitoring during amiodarone treatment.

Severe Hypocalcemia Occurring During the Hospitalization of a Patient Affected by Permanent Post-Surgical Hypoparathyroidism with Multimorbidity: A Case Report.

BACKGROUND: Patients with permanent hypoparathyroidism experience an impaired quality of life, due to acute and chronic complications that may affect several organs, with an increased risk of hospitalisation and death. Adequate and continuous replacement therapy with calcium and calcitriol is necessary to avoid symptoms and long-term complications related to hypocalcemia. CASE PRESENTATION: A 63 years old male, affected by permanent post-surgical hypoparathyroidism, was hospitalized in the cardiology department because of a dehiscence of the subcutaneous housing of the double-chambered implantable cardioverter-defibrillator. Chronic replacement therapy for hypoparathyroidism was poorly controlled and, during hospitalization, severe hypocalcemia occurred together with electrocardiographic and echocardiogram life-threatening alterations. CONCLUSION: Constant and targeted long-term replacement therapy with calcium and particularly calcitriol is necessary to avoid major consequences on patients' health, especially during acute events and in the presence of other comorbidities.

The role of mitochondrial dysfunction in the association between trace metals and QTc prolongation in the aged population.

This study delves into the relationship between environmental metal exposure and QT interval corrected for heart rate (QTc) prolongation, a critical marker for cardiovascular risk in the elderly. Although the interplay between metal exposure and QTc prolongation is important for predicting sudden cardiac death, it remains underexplored. Our analysis of 6478 participants from the Shenzhen aging-related disorder cohort involved measuring urinary concentrations of 22 trace metals and using mitochondrial DNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Utilizing Bayesian kernel machine regression, and structural equation modeling, we assessed the effects of mixed trace metals on QTc prolongation. Our findings indicated a direct association between certain metals (Sb, Cu, Zn) and a 7 % increase in QTc prolongation risk, while Li, V, and Rb were associated with a 5 % reduction in risk. Elevated levels of V, Ti, and Cr corresponded to higher mtDNA-CN. Notably, restricted cubic splines revealed a U-shaped, nonlinear relationship between mtDNA-CN and QTc prolongation. After adjusting for metal exposure, an inverse correlation was observed between mtDNA-CN and QTc prolongation, suggesting mitochondrial dysfunction as a partial mediator.

Impact of preoperative QTc interval prolongation on short-term postoperative outcomes: A retrospective study.

STUDY OBJECTIVE: Although a prolonged heart rate-corrected QT interval (QTcI) is associated with an increased risk of mortality in the general population, its prognostic value in surgical patients remains unclear. We aimed to examine whether preoperative QTcI prolongation predicts short-term postoperative outcomes in elderly patients undergoing noncardiac surgery. DESIGN: The study was a retrospective analysis using the TriNetX network database. SETTING: Operating room. INTERVENTION: Assessment and categorization of preoperative QTcI. PATIENTS: Data of patients aged ≥65 years who underwent non-cardiac surgery between 2010 and 2023 were analyzed. MEASUREMENTS: Patients were categorized into four groups based on preoperative QTcI: long (500-600 ms), borderline (460-500 ms), high-normal (420-460 ms) and control (370-420 ms) groups. The groups were compared using a propensity score-matched analysis. The primary outcome was the all-cause 90-day mortality risk. The secondary outcomes included 90-day risks of postoperative new-onset atrial fibrillation (Af), ventricular arrhythmias (VAs), emergency visits, hospital readmissions, and pneumonia. RESULTS: In total, data on 519,929 patients were collected in this study. Pairwise comparisons showed that all QTcI prolongation groups demonstrated a heightened incidence of postoperative mortality, arrhythmias, and other complications compared to the control group. Patients with a long QTcI had a 3-fold higher risk of mortality (hazard ratio [HR] = 3.124, p < 0.001), Af (HR = 3.059, p < 0.001), and VAs (HR = 3.617, p < 0.001) than controls. The risks of emergency visits (HR = 1.287, p < 0.001), hospital readmissions (HR = 1.591, p < 0.001), and pneumonia (HR = 1.672, p < 0.001) were also higher in the long QTcI group than in the control group. A dose-dependent response was evident between QTcI and mortality as well as arrhythmia risk. CONCLUSION: Preoperative QTcI screening effectively risk-stratifies elderly surgical patients, with a QTcI≥500 ms being strongly predictive of short-term postoperative mortality and other complications. Incorporating QTcI assessment into the preoperative evaluation may guide perioperative monitoring and management.

ß-Adrenoceptor blockade can augment the torsadogenic action of risperidone.

Risperidone is a second-generation antipsychotic for treating schizophrenia and bipolar disorder. It can potently inhibit IKr, but is classified into conditional risk for torsade de pointes (TdP) by CredibleMeds®. Our previous studies using chronic atrioventricular block dogs showed that risperidone alone did not induce TdP, and that dl-sotalol (ß-adrenoceptor blockade plus IKr inhibition) induced TdP three times more frequently than d-sotalol (IKr inhibition alone). Since risperidone can block α1-adrenoceptor and decrease blood pressure, the resulting reflex-mediated increase of sympathetic tone on ß-adrenoceptor might protect the heart from its IKr inhibition-associated TdP. To validate this hypothesis, risperidone was administered to chronic atrioventricular block dogs after ß-adrenoceptor blocker atenolol infusion with monitoring J-Tpeak and Tpeak-Tend, which are proarrhythmic surrogate markers of "substrate" and "trigger" toward TdP, respectively. Atenolol alone induced TdP in 1 out of 5 dogs; moreover, an additional infusion of risperidone induced TdP in 3 out of 4 dogs. Risperidone prolonged QT interval, J-Tpeak and Tpeak-Tend in animals that induced TdP. These findings indicate that ß-adrenoceptor blockade can diminish repolarization reserve to augment risperidone's torsadogenic potential, thus advising caution when using ß-adrenoceptor blockers in patients with IKr inhibition-linked labile repolarization.

No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects.

Cardiotoxicity and QT interval prolongation have been a common cause of withdrawal of drugs from the market. FCN-437c is an oral, second-generation, potent, and selective CDK4/6 inhibitor for the treatment of patients with HR+/HER2- metastatic breast cancer. A single-center, double-blind, randomized, and placebo-controlled clinical study in healthy subjects was conducted to investigate the QTc prolongation potential of FCN-437c utilizing Concentration-QTc (C-QTc) modeling approach. FCN-437c was administered at doses of 300, and 400 mg with single oral administration, along with placebo, in 18 healthy subjects. Electrocardiograms (ECGs) through 24 h holter monitor and blood samples were collected. The Cmax of 400 mg single dose in healthy subjects is similar to that from therapeutic dose 200 mg QD at steady state in patients with cancer. The 90% CI upper limit of ΔΔQTcF at the Cmax geometric mean in both dose groups were <10 ms. It is concluded that FCN-437c has low risk of prolonging the QT interval at therapeutic dose. Systematic Review Registration: https://clinicaltrials.gov/study/NCT06290466?term=NCT06290466&rank=1, identifier [NCT06290466].

Ventricular unloading causes prolongation of the QT interval and induces ventricular arrhythmias in rat hearts.

Introduction: Ventricular unloading during prolonged bed rest, mechanical circulatory support or microgravity has repeatedly been linked to potentially life-threatening arrhythmias. It is unresolved, whether this arrhythmic phenotype is caused by the reduction in cardiac workload or rather by underlying diseases or external stimuli. We hypothesized that the reduction in cardiac workload alone is sufficient to impair ventricular repolarization and to induce arrhythmias in hearts. Methods: Rat hearts were unloaded using the heterotopic heart transplantation. The ECG of unloaded and of control hearts were telemetrically recorded over 56 days resulting in >5 × 106 cardiac cycles in each heart. Long-term electrical remodeling was analyzed using a novel semi-automatic arrhythmia detection algorithm. Results: 56 days of unloading reduced left ventricular weight by approximately 50%. While unloading did not affect average HRs, it markedly prolonged the QT interval by approximately 66% and induced a median tenfold increase in the incidence of ventricular arrhythmias in comparison to control hearts. Conclusion: The current study provides direct evidence that the previously reported hypertrophic phenotype of repolarization during cardiac unloading translates into an impaired ventricular repolarization and ventricular arrhythmias in vivo. This supports the concept that the reduction in cardiac workload is a causal driver of the development of arrhythmias during ventricular unloading.

Comparison of corrected QT (QTc) interval of electrocardiogram calculated from various formulas.

QT interval in an electrocardiogram (ECG) is interpreted after correction (QTc) by various formulas. This study aimed to compare the QTcs calculated by nine formulas. Sinus rhythm ECG reports of 1140 anonymous subjects showed uncorrected QT interval of 388.49 ± 42.74 ms. The QTc calculated by Bazett (443.96 ± 57.58 ms), Fridericia (424.37 ± 50.1 ms), Dmitrienko (433.59 ± 53.37 ms), Framingham (422.59 ± 45.55 ms), Schlamowitz (433.89 ± 48.05 ms), Hodges (421.6 ± 46.4 ms), Ashman (434.33 ± 54.05 ms), Rautaharju (427.75 ± 47.4 ms), and Sarma (429.22 ± 48.67 ms) showed a significant difference F (8, 10251) = 22.78 p < 0.0001. Hence, ECG should contain the formula for proper reporting and ease of interpretation by clinicians.

Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.

Effect of Empagliflozin Treatment on Ventricular Repolarization Parameters.

Background: An example of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor is Empagliflozin. It is a new medicine for treating type 2 diabetes mellitus (T2DM), but there is increasing interest in how empagliflozin affects the heart. This study aims to examine the impact of empagliflozin treatment on ventricular repolarization parameters in T2DM patients. Methods: T2DM patients were included in a prospective study. Measurements of ventricular repolarization parameters, including QT interval, corrected QT interval (QTc), QT dispersion (QTd), Tpeak-to-Tend interval (Tp-e), and Tpeak-to-Tend interval corrected for QTc (Tp-e/QTc), were obtained before initiating empagliflozin treatment and six months following treatment initiation. Statistical analysis was performed to assess changes in these parameters. Results: In this study, 95 patients were diagnosed with T2DM out of 177 patients. Among T2DM patients, 40 were male (42%) compared to 48% males in controls (p = 0.152). The average age of the T2DM patients was 60.2 ± 9.0 years, compared to 58.2 ± 9.2 years in the control group (p = 0.374). When comparing pre- and post-treatment measurements of parameters representing ventricular repolarization (QT 408.5 ± 22.9/378.8 ± 14.1, p < 0.001; QTc 427.0 ± 20.5/404.7 ± 13.8, p < 0.001; QTd 52.1 ± 1.2/47.8 ± 1.7, p < 0.001; Tp-e 82.3 ± 8.7/67.1 ± 5.1, p < 0.001; Tp-e/QTc 0.19 ± 0.01/0.17 ± 0.01, p < 0.001 (respectively)), statistically significant improvements were observed. A statistically significant dose-dependent decline in the magnitude of change in the QTc parameter (19.4/29.6, p = 0.038) was also observed. Conclusions: According to these results, empagliflozin may decrease the risk of potential ventricular arrhythmias.

Exploring the multiple effects of nifedipine and captopril administration in spontaneously hypertensive rats through pharmacokinetic-pharmacodynamic analyses.

This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated. The coadministration of nifedipine and captopril resulted in an increase in nifedipine's total body clearance (CLtot) and a reduction in its mean residence time (MRT) with an increase in the terminal elimination half-life (t1/2) and volume of distribution at steady state (Vdss) of captopril. However, no significant PK interactions were observed. During monotherapy, BP reduced rapidly following nifedipine infusion. Subsequently, despite the increase in nifedipine plasma concentration, BP recovered, likely because of homeostasis. Similar results were observed with coadministration. Subsequently, BP demonstrated a sustained reduction that was greater than or equal to the additive effect estimated from each PK. Captopril exhibited a minimal effect on HR, except for a transient increase observed immediately after starting infusion, consistent with observations during coadministration. Subsequently, the HR reduction was nearly equal to that calculated from the nifedipine PK. QT prolongation was more rapid with captopril than with nifedipine. Although QT prolongation during the initial 60 min of coadministration was approximately the sum of both effects, the recovery period to baseline QT was faster than that in the simulation.

Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.

Association Between Disturbed Serum Phosphorus Levels and QT Interval Prolongation.

Introduction: QT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in patients on hemodialysis (HD) is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in patients on HD and to verify the association between predialysis serum calcium (Ca) and phosphate (P) levels and QT interval prolongation. Methods: A cross-sectional study was conducted on adult patients on maintenance HD who were enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with predialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome. Results: A total of 204,530 patients were analyzed with a mean QTc of 451.2 (standard deviation, 36.9) ms. After multivariable analysis, estimated change in QTc (coefficients; 95% confidence interval) per 1 mg/dl increase in serum Ca and P was -2.02 (-3.00 to -1.04) and 5.50 (3.92-7.09), respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve. Conclusion: Decreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in patients on maintenance HD.