Effect of Dapagliflozin on Electrocardiographic Parameters in Type 2 Diabetes Patients: DAPA - ECG Study

In the intervention group (dapagliflozin), 12-lead electrocardiograms (ECGs) were performed during designated outpatient visits, with the initial baseline recording conducted at visit 1 (day 0) and the subsequent recording at the final visit, approximately 90 days after the study began.

The ECGs were obtained using Micromed electronic equipment, configured with a paper speed of 25 mm/s and an amplitude of 10 mm/mV, ensuring standardized measurements. The ECG intervals were manually measured using Wincardio software (version 11.1.0.0).

The primary outcome, the interval between the peak of the T wave and the end of the T wave (TpTe), was assessed to evaluate the effect of dapagliflozin. This assessment compared the two time points (baseline and follow-up), with all ECGs analyzed by an independent external examiner to ensure objectivity and reliability of the study results.

In the intervention group (dapagliflozin), 12-lead electrocardiograms (ECGs) were performed during designated outpatient visits, with the initial baseline recording conducted at visit 1 (day 0) and the subsequent recording at the final visit, approximately 90 days after the study began.

The ECGs were obtained using Micromed electronic equipment, configured with a paper speed of 25 mm/s and an amplitude of 10 mm/mV, ensuring standardized measurements. The ECG intervals were manually measured using Wincardio software (version 11.1.0.0).

The secondary outcomes, the QT and corrected QT (QTc) intervals, were assessed to evaluate the effect of dapagliflozin. These intervals were analyzed by comparing the two time points (baseline and follow-up). All ECGs were reviewed by an independent external examiner, ensuring objectivity and reliability in the interpretation of the study data.

To evaluate the effect of dapagliflozin on the TpTe/QT ratio, an electrocardiographic marker of arrhythmogenesis that reflects the degree of heterogeneity in myocardial repolarization. The TpTe interval, measured as the time from the peak of the T wave to the end of the T wave, and the TpTe/QT ratio, calculated by dividing the TpTe interval by the QT interval, were assessed at baseline (visit 1, day 0) and follow-up (final visit, approximately 90 days later).

Prolonged TpTe and TpTe/QT intervals are associated with a higher risk of sudden cardiac death (SCD) in various cardiac conditions, including hypertrophic cardiomyopathy and long QT syndrome, making them valuable prognostic markers. In this study, 12-lead ECGs were recorded using Micromed electronic equipment (configured at a paper speed of 25 mm/s and amplitude of 10 mm/mV), and intervals were manually measured with Wincardio software (version 11.1.0.0).

The J-Tp interval (JTp), an important marker of delays in the early phase of the action potential, was measured from the J point to the peak of the T wave (Tp) on 12-lead electrocardiograms (ECGs). Baseline ECG recordings were conducted at visit 1 (day 0), while follow-up recordings were obtained approximately 90 days later at the final visit.

All ECGs were recorded using Micromed electronic equipment, standardized with a paper speed of 25 mm/s and an amplitude of 10 mm/mV. Manual measurements of the JTp interval were performed using Wincardio software (version 11.1.0.0). This parameter was assessed to evaluate the effect of dapagliflozin on early ventricular repolarization dynamics, providing valuable insights into potential delays in the initial phase of the cardiac action potential and contributing to the overall understanding of its impact on cardiac electrophysiology.

QT interval dispersion (QTd), a marker of spatial heterogeneity in ventricular repolarization, was calculated as the difference between the longest (QTmax) and shortest (QTmin) QT intervals measured on 12-lead electrocardiograms (ECGs). Baseline ECG recordings were taken at visit 1 (day 0), and follow-up recordings were acquired approximately 90 days later at the final visit.

The ECGs were obtained using Micromed electronic equipment, configured with a paper speed of 25 mm/s and an amplitude of 10 mm/mV. All interval measurements were manually conducted using Wincardio software (version 11.1.0.0) to ensure precision and standardization.

This parameter was analyzed to assess the impact of dapagliflozin on reducing ventricular repolarization dispersion, which has been associated with an increased risk of arrhythmias and sudden cardiac death (SCD) in patients with type 2 diabetes.

The QRS-T angle, a vectorcardiographic marker of ventricular repolarization heterogeneity and electrical dyssynchrony, was evaluated using data obtained from 12-lead electrocardiograms (ECGs). Baseline ECGs were recorded at visit 1 (day 0), and follow-up recordings were performed approximately 90 days later at the final visit.

The QRS-T angle was calculated by analyzing the electrical axes of the QRS complex and the T wave in the frontal plane leads. These measurements were performed using the MYEKG software, which processed the R and T wave amplitudes in millimeters and calculated the spatial QRS-T angle using a dedicated algorithm available at [https://pt.my-ekg.com/calculadoras-ecg/calculadora-eixo-eletrico.php].

The QRS-T angle was categorized into three groups: normal (0 to 105°), borderline (105 to 135°), and abnormal (135 to 180°). This parameter was assessed to determine the impact of dapagliflozin on ventricular electrical heterogeneity

Heart rate was measured from 12-lead electrocardiograms (ECGs) recorded during designated outpatient visits. Baseline ECG recordings were obtained at visit 1 (day 0), and follow-up ECGs were performed approximately 90 days later at the final visit.

The ECGs were recorded using Micromed electronic equipment, standardized with a paper speed of 25 mm/s and an amplitude of 10 mm/mV. Heart rate measurements were automatically calculated by the Wincardio software (version 11.1.0.0) and manually verified when necessary to ensure precision and consistency.

This parameter was evaluated to assess the effect of dapagliflozin on overall cardiac rhythm and rate regulation in patients with type 2 diabetes. Independent external examiners reviewed all ECGs to ensure objectivity and reliability in the study data.

The measurement of glycated hemoglobin (HbA1c %) was performed through venous blood collection, with samples sent for analysis in a certified laboratory in accordance with the international quality standards established by the National Glycohemoglobin Standardization Program (NGSP) and aligned with the reference methods of the International Federation of Clinical Chemistry (IFCC).

The collected data were recorded in the study's digital Case Report Form (CRF) during the baseline visit and again after 90 days, at the end-of-study visit.

he participants' weight (Kg) was measured using a properly calibrated scale, with participants standing upright, barefoot, and wearing light clothing. The data were recorded in the study's digital Case Report Form (CRF) during the baseline visit and again after 90 days, at the end-of-study visit, to monitor any changes associated with the treatment or clinical progression.

The participants' Body Mass Index (BMI) was calculated using the formula weight (kg) divided by height squared (m²), based on measurements obtained during the baseline visit. Weight was measured using a properly calibrated scale, and height was measured with a stadiometer, with participants standing barefoot and in an upright position. The BMI data were recorded in the study's digital Case Report Form (CRF) during the baseline visit and again after 90 days, at the end-of-study visit, to assess any changes associated with the treatment or clinical progression.

The participants' systolic and diastolic blood pressure (BP) was measured in millimeters of mercury (mmHg) using a properly calibrated automated or manual sphygmomanometer. Measurements were taken with participants seated, at rest for at least five minutes, and with their arm supported at heart level. Blood pressure readings were recorded in triplicate, with the average value documented for accuracy.

The systolic and diastolic BP data were entered into the study's digital Case Report Form (CRF) during the baseline visit and again after 90 days, at the end-of-study visit, to monitor any changes associated with the treatment or clinical progression.

The participants' glomerular filtration rate (GFR) was estimated in milliliters per minute per 1.73 square meters (mL/min/1.73 m²) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This calculation was based on serum creatinine levels, age, sex, and race, obtained from blood samples analyzed in a certified laboratory.

The GFR data were recorded in the study's digital Case Report Form (CRF) during the baseline visit and again after 90 days, at the end-of-study visit, to evaluate renal function changes associated with the treatment or clinical progression.

The echocardiographic parameter left ventricular ejection fraction (LVEF), expressed as a percentage (%), was evaluated using standard transthoracic echocardiography (TTE).

All measurements were conducted by certified sonographers using clinically approved equipment, adhering to the guidelines established by the American Society of Echocardiography (ASE). Data collected during the echocardiographic assessments were systematically documented in the study's digital Case Report Form (CRF). Evaluations were performed both at the baseline visit and at the end-of-study visit (90 days) to monitor potential structural or functional cardiac changes related to the treatment or clinical progression.

The echocardiographic parameter left ventricular end-diastolic diameter (LVEDD), measured in millimeters (mm), was evaluated using standard transthoracic echocardiography (TTE).

All measurements were performed by certified sonographers using clinically validated equipment, in compliance with the guidelines of the American Society of Echocardiography (ASE). The obtained echocardiographic data were systematically recorded in the study's digital Case Report Form (CRF). Assessments were conducted at the baseline visit and at the end-of-study visit (90 days) to track any structural cardiac changes associated with treatment or clinical progression.

The echocardiographic parameter left ventricular systolic diameter (LVSD), measured in millimeters (mm), was assessed using standard transthoracic echocardiography (TTE).

All measurements were performed by certified sonographers utilizing clinically validated equipment, in accordance with the guidelines of the American Society of Echocardiography (ASE). The recorded data were systematically entered into the study's digital Case Report Form (CRF). Measurements were obtained at both the baseline visit and the end-of-study visit (90 days) to evaluate potential changes in ventricular dimensions associated with treatment or clinical progression.

The echocardiographic parameter left atrial diameter (LAD), measured in millimeters (mm), was assessed using standard transthoracic echocardiography (TTE).

All measurements were performed by trained and certified sonographers utilizing clinically validated equipment, in accordance with guidelines provided by the American Society of Echocardiography (ASE). The collected LAD data were systematically recorded in the study's digital Case Report Form (CRF) during the baseline visit and again at the end-of-study visit (90 days) to evaluate potential changes in left atrial size associated with treatment effects or clinical progression.

The use of key medications, including beta-blockers, propafenone, amiodarone, renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors), angiotensin II receptor blockers (ARBs), sacubitril-valsartan, and mineralocorticoid receptor antagonists (MRAs), was documented for each participant. Information on medication type, dose, and frequency was collected during interviews and confirmed through medical records.

These data were systematically recorded in the study's digital Case Report Form (CRF) during the baseline visit and again after 90 days, at the end-of-study visit, to monitor ongoing treatment regimens and assess their potential influence on clinical outcomes.

The variable for hospitalization within 90 days was recorded as a categorical variable (Yes/No). These data were collected during the final visit at 90 days, based on self-reported information provided by the participant or through active data retrieval from medical records and hospital databases to ensure accuracy.

The hospitalization data were documented in the study's digital Case Report Form (CRF) during the 90-day visit to assess the occurrence of hospital admissions during the study period and their potential influence on outcomes.

The variable for all-cause mortality was recorded as a categorical variable (Yes/No). These data were collected during the final visit at 90 days through direct communication with the participant's family or caregiver, or via active data retrieval from medical records, hospital databases, or public death registries to ensure accuracy.

The all-cause mortality data were documented in the study's digital Case Report Form (CRF) at the 90-day visit to assess the occurrence of death from any cause during the study period and its potential impact on clinical outcomes.

The cause of death was recorded as a categorical variable, classified as either cardiovascular death or non-cardiovascular death. These data were collected during the final visit at 90 days through direct communication with the participant's family or caregiver, or via active data retrieval from medical records, hospital databases, or public death registries. For cardiovascular deaths, the classification was based on standard clinical definitions, including sudden cardiac death, death due to myocardial infarction, stroke, or other cardiovascular causes.

The cause-of-death data were documented in the study's digital Case Report Form (CRF) at the 90-day visit to differentiate between cardiovascular and non-cardiovascular mortality and to assess its potential influence on clinical outcomes.