|Year : 2017 | Volume
| Issue : 3 | Page : 86-91
QT corrected for heart rate and qtc dispersion in Gujarati type 2 diabetics predominantly using preventive pharmacotherapy and with very low electrocardiogram left ventricular hypertrophy
Jayesh Dalpatbhai Solanki1, Kruti J Patel2, Nisha Lalwani2, Hemant B Mehta1, Chinmay J Shah1, Matika N Lakhtaria2
1 Department of Physiology, GMC, Bhavnagar, Gujarat, India
2 Department of Medicine, GMC, Bhavnagar, Gujarat, India
|Date of Web Publication||29-Dec-2017|
Jayesh Dalpatbhai Solanki
Department of Physiology, Fourth Floor, Government Medical College, Bhavnagar, Bhavnagar - 364 001, Gujarat
Source of Support: None, Conflict of Interest: None
Background: There is a rising trend in the incidence of type 2 diabetes mellitus, and hyperglycaemia is known to cause cardiac dysautonomia, which may lead to life-threatening arrhythmias. It can be screened by simple electrocardiogram (ECG)-based QTc (QT corrected for heart rate) and QTd (QTc dispersion) indicating cardiac repolarisation abnormality. We studied QTc and QTd intervals in treated type 2 diabetics (T2D), testing the effect of age, gender, duration and control of disease. Materials and Methods: We conducted a cross-sectional study in a tertiary care teaching hospital of Gujarat, India, on 199 T2D (67 males and 132 females). Standard 12-lead ECG was recorded to derive QTc by Bazett's formula, QTd and ECG left ventricular hypertrophy (LVH). QTc >0.43 s in male and >0.45 s in female, QTd >80 msec were considered abnormal. Results: T2D (mean age 56 years, duration 6 years, coexisting hypertension 69%, glycaemic control 32% and use of β-blockers 56%) had QTc and QTd abnormality prevalence 15% and 20% respectively with ECG LVH prevailing in 3%. Male gender, poor glycaemic control and increased duration had negative impact on QT parameters with statistical significance only for first two and not for all results. Conclusion: Our study showed low-to-moderate prevalence of prolonged QTc and QTd, qualitatively more than quantitatively, in T2D with very low LVH and high prevalence of preventive pharmacotherapy, associated with male gender and glycaemic control. It underscores high risk of repolarisation abnormality, though moderate, that can be further primarily prevented by early screening and strict disease control.
Keywords: Diabetes, hyperglycaemia, hypertrophy, left ventricular, repolarisation
|How to cite this article:|
Solanki JD, Patel KJ, Lalwani N, Mehta HB, Shah CJ, Lakhtaria MN. QT corrected for heart rate and qtc dispersion in Gujarati type 2 diabetics predominantly using preventive pharmacotherapy and with very low electrocardiogram left ventricular hypertrophy. J Diabetol 2017;8:86-91
|How to cite this URL:|
Solanki JD, Patel KJ, Lalwani N, Mehta HB, Shah CJ, Lakhtaria MN. QT corrected for heart rate and qtc dispersion in Gujarati type 2 diabetics predominantly using preventive pharmacotherapy and with very low electrocardiogram left ventricular hypertrophy. J Diabetol [serial online] 2017 [cited 2018 Jul 20];8:86-91. Available from: http://www.journalofdiabetology.org/text.asp?2017/8/3/86/222086
| Introduction|| |
There is alarming rise of type 2 diabetes mellitus (T2DM) in India, a disease having multiple unfavourable effects on the heart. There is suboptimal disease control, lack of awareness and negligence towards early screening or primary prevention of various known cardiovascular aftermaths of type 2 diabetes. Abnormal cardiac repolarisation is seen in uncontrolled diabetics that can progress to life-threatening arrhythmia. However, same can be diagnosed by simple electrocardiogram (ECG)-based QTc (QT corrected for heart rate) and QTd (QTc dispersion) and prevented by pharmacotherapy. With increased duration of disease, poor glycaemic control  and in the presence of various risk factors abnormality further worsens. Against this background, we quantified QT parameters in uncomplicated type 2 diabetics (T2D) and studied various correlates for it.
| Materials and Methods|| |
This cross-sectional study was conducted in the Medicine department in association with Physiology department of Government Medical College, Bhavnagar, Gujarat, India.
After approval from the Institutional ethical Committee and written informed consent from each participant, volunteers were recruited for this study. Of a total number of participants who attended the outdoor clinic, all the adult participants were screened for the presence of type 2 diabetes. Participants coming to the clinic with record of treatment of diabetes were also included in this screening for confirmation. Of a total number of patients with type 2 diabetes, observed during the recruitment period (n = 400), 199 patients were consecutively selected for this study. Sample size was calculated by software Raosoft (Raosoft, Inc. free online software, Seattle, WA, USA). A sample of 199 participants for a population of 6 lakh with 7.33% prevalence of T2DM in our region gave us 95% confidence level, leaving 5% margin of error.
Inclusion and exclusion criteria
We enrolled T2D, with duration of at least 1 year and known current glycaemic control, aged 30–70 years, of either sex, with or without hypertension taking treatment (except insulin) regularly (through chart review), ready for written consent.
Exclusion criteria were those patients with duration <1 year of diabetes (n = 18), taking treatment of diabetes irregularly (n = 17), age >70 years (n = 140), chronic dysentery (n = 0), patients having cancer (n = 0), chronic kidney failure (n = 4), type 1 diabetes (n = 30), past history of cardiovascular intervention, on pacemaker (n = 0), drug therapy influencing autonomic function other than β-blocker (n = 70) and non-volunteers (n = 2) were excluded. None of the participants was using dipeptidyl peptidase 4 inhibitors.
Collection of data
After a 5-min rest, a blood pressure (BP) was recorded in a sitting position, on the right arm with a standard mercury manometer. Every participant had two readings, with the average of these reading recorded as the resting BP. To minimise measurement errors, one individual was assigned to measure BP for all the participants in both the groups. In accordance with the WHO guidelines, if a BP of more than ≥140/90 mmHg was recorded, a repeat measurement was obtained after a 5-min rest, with the subject in a supine position.
QT corrected for heart rate measurement
We used 12-channel ECG machine to record strip ECG with standard norms. Participants were asked to lie in supine position, and 12-lead ECG was recorded on ECG machine. QT interval and RR interval were measured manually from the ECG strip for 10 successive readings. QT interval was measured using tangent method. RR interval was measured from one R-wave peak to another R-wave peak. QTc intervals were derived using Bazett's formula and average of 10 results was taken for each participant. Seven cases were discarded since lead II had artefact or shallow T -wave as well as difficult measurement of the QT.
QTc = QT
No correction was used if heart rate was <60.
ECG left ventricular hypertrophy (LVH) criteria :
We used the Cornell voltage criteria to define LVH which is as follows-
- S in V3 + R in aVL >28 mm (men)
- S in V3 + R in aVL >20 mm (women).
We defined glycaemic control as per criteria laid by the American Diabetes Association 2014, and good glycaemic control was defined as (1) FPG ≤126 mg% and (2) PP2BG ≤180 mg%.
QTc and QTd were analysed in two ways:
- Quantitative comparison-comparing absolute QT values
- Qualitative comparison-comparing frequency of normal or prolonged QT defined as per standard cutoffs.
QTc value >0.43 s in male and >0.45 s in female and QTd value >80 ms were considered abnormal.
Systolic BP (SBP) <140 mmHg and diastolic BP <90 mmHg was defined as controlled BP.
The data were transferred on Excel Spreadsheet; descriptive analysis was expressed as mean ± standard deviation and categorical data as number (percentage). All calculations were done by GraphPad InStat 3 statistical software (demo version free software of GraphPad Software, Inc. California, USA). Observed difference in the mean distribution of QTc intervals was compared by student's t-test. We evaluated the strength of association between QTc and various parameters by calculating odds ratio, keeping confidence interval 95%, taking QTc >0.43 s in males and QTc >0.45 s in females as positive outcomes and QTc ≤0.43 s in males and QTc ≤0.45 s in females as negative outcome. Difference in distribution of categorical data between groups was tested by Fisher's exact test. Any observed difference was considered significant statistically with P < 0.05.
| Results|| |
Our study group had mean age 56 years, preponderance of female gender (66%) and mean duration of diabetes 6 years with poor glycaemic control (32%) and moderate BP control (51%), whereas coexistence of hypertension was high (69%). Most of type 2 diabetes patients are taking biguanides except two patients.
Use of other drugs affecting cardiovascular outcome was statins (48%), aspirin (32%), β-blockers (56%), ACE inhibitors (29%).
Males were significantly elder (mean-59 vs. 54, P < 0.001) and with longer disease duration than females (mean-7 vs. 5, P= 0.01).
Otherwise, both gender-based subgroups were comparable with reference to glycaemic control, BP control and prevalence of use of pharmacotherapy [Table 1].
|Table 1: Baseline and clinical data of study participants-whole group and gender wised|
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ECG-based parameters showed average QTc 0.42 s and QTd 47.8 msec in whole group with the prevalence of abnormal QTc, QTd and ECG LVH (15%, 20% and 3%, respectively). As compared to females, males had insignificantly higher quantitative QTc and QTd. The prevalence of abnormal QTc was significantly higher in males compared to females (QTc-22% vs. 11%, P= 0.034). The prevalence of prolonged QTd and ECG LVH were not much different between these subgroups [Table 2].
|Table 2: Electrocardiogram parameters of the study group-gender wise and in total|
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We divided study participants into two subgroups with disease duration more than or less than 5 years, keeping them comparable for gender distribution, disease control and use of preventive pharmacotherapy. Participants with longer duration had higher prevalence of qualitative QTc prolongation as compared to those with <5-year duration (17% vs. 12%, P= 0.418). Other QT parameters were better with less duration but differences were insignificant statistically [Table 3].
|Table 3: Comparison of study parameters between participants with diabetes duration ≥5 years (n=113) and <5 years (n=86)|
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Based on the American Diabetes Association 2014 guidelines, participants were divided into the group with good glycaemic control or poor glycaemic control. These two subgroups were not different in baseline data, disease control or drugs used. Group with poor glycaemic control had high mean QTc (P 0.003) and higher prevalence of prolonged QTd (24% vs. 11%, P= 0.036) as compared to the group with good glycaemic control. Later group had small, insignificantly better qualitative QTc and quantitative QTd than former group [Table 4].
|Table 4: Comparison of study parameters between good glycaemics (n=64) and poor glycaemics (n=135)|
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| Discussion|| |
Cardiovascular complications are well documented in type 2 diabetes, but cardiac autonomic neuropathy is neglected. Cardiac dysautonomia is known in T2DM ,, and can be screened by various tests to judge cardiac autonomic balance. We compared effect of type 2 diabetes on cardiac autonomic balance judged by simple ECG-based QT intervals.
We found low-to-moderate prevalence of abnormally prolonged QTc (15%) and QTd (20%) in ambulatory-treated T2D. This is more than the prevalence of QT abnormality found in normal healthy participants in our region. Although, our diabetic group revealed a prevalence, lesser than other similar studies., This can be attributed to two of the main factors, low prevalence of LVH in ECG and use of preventive pharmacotherapy. QT prolongation marks the heterogenicity of left ventricular mass that correlates with LVH  seen in patients with diabetes  and more so in hypertensive diabetics (which comprised of more than two-third of our cases). Very low LVH prevalence (3%) explains the lower incidence of QTc or QTd abnormalities. There are studies showing QT prolongation in the absence of LVH, but still 'low LVH leads to low-QT abnotmality' holds true in our cases. This becomes even significant with the fact that only one-third diabetics had optimum glycaemic control, whose the absence is risk factor for QT interval prolongation. The second possible factor for lower than expected QT abnormality is the presence of co-existing hypertension which brings the additive risk  but also offers the benefit of use antihypertensive drugs. Normotensive diabetics not receiving this preventive pharmacotherapy such as beta-blockers, first-line antihypertensives and aspirin are not offered this benefit. Beta-blockers have beneficial effect on QT interval as previously documented  and we found the same, evident as low-QT abnormality in patients with diabetes with use of beta-blocker in majority (56%). A recent study  has shown that beta-blockers in T2DM prevent hypoglycaemia-related complications such as hypertension, hypokalemia, QT prolongation, cardiac arrhythmia and sudden cardiac death. As compared to with beta-blocker, intensive glycaemic control without beta-blocker, has found to have increased all-cause and cardiovascular mortality, and this study gives a re-affirmative clue to that. In our previous study, we found that use of antihypertensive drug mainly ACE inhibitor gives better profile of diabetic vasculopathy in hypertensive diabetics as compared to normotensive diabetics not receiving the same. Hence, the preventive effect of these drugs in our study group can be understood that was applicable to hypertensives, consisting of 2 out of three participants.
We had males with worse QT profile than females, having mean age in mid-fifties, in contrast to few studies done in younger age group., The mean age beyond menopausal age explains the absence of female advantage due to hormones. and our result is supported by another study with broad age group of normal healthy Indians. Another reason for the male disadvantage may be higher mean age (59 vs. 54) and disease duration (7 vs. 5 years) in males than females. Duration did not affect results of QT parameters significantly in contrast with the previous studies., It can be due to delay in diagnosis, delay in onset of treatment, poor glycaemic control and low self-care despite increasing duration. Poor glycaemic control and its effect on cardiovascular study parameters known in our type 2 diabetics,, same being true in the current study. Hyperglycaemia imposes direct damage to cardiac myocyte. Good diabetic control may reduce the prevalence of QT abnormality from 15% to 20% to the normal level of 5%–10%.
Our recent study showed a high prevalence of prolonged QTc, both qualitatively and quantitatively, in hypertensives of our region on monotherapy (n = 142, mean age 40 years, 58% males) with poor pressure control, associated with female gender and age but not duration or BP. The same study also showed  prolonged QTc more so in newly diagnosed hypertensives, unaffected by duration of hypertension or use of ACEI or CCB but associated with modifiable risk factors. These two results are just alike current study done focusing diabetes instead of hypertension. Both conditions have common risk factors, associates and aftermaths, increasing trend and silent progressing nature. It suggests that early screening, better disease control, ECG monitoring and lifestyle interventions, all can serve as good preventive measures. Prolonged QTc and QTd indicates heterogenicity of ventricular depolarisation. This is due to an underlying change in ion channels responsible for the synchronised electrical activity. Prolonged repolarisation leaves a scope for circus movement of electrical impulse. This can lead to ventricular arrhythmia that begins as premature ventricular contraction. T2D have more likelihood of cardiovascular diseases, more so when the diagnosis is delayed, HbA1c reports are unavailable, lifestyle modifications are neglected, awareness is less and screening tools such as ECG and HRV are sparely used. ECG is a simple diagnostic tool that can be practised even at primary health care level. A simple rule of 50 can be used to detect arrhythmia risk early which states that QT interval should be normally <50% of RR interval. However, it is undertreated and underused in asymptomatic, at-risk patients such as patients with diabetes or hypertensives. QTc and QTd are validated diagnostic tools available since long. QTc >440 msec and QTd >80 msec are known individual predictor of CVD events. It becomes more useful in T2DM than myocardial infarction or congestive heart failure as ECG baseline is stable and other arrhythmia are absent. T2DM is incurable lifelong companion where quality of life and longevity are endangered by cardiovascular risk. Healthy heart is a key to apparently healthy life in diabetics, but it needs assurance by timely screening and benefit of glycaemic control.
This study was limited by manual method of measurement, moderate sample size, unavailability of HbA1c, the absence of biochemical parameters, the presence of confounding factors. We did not have other tests to detect cardiac dysautonomia and various macrovascular and microvascular complications were not studied. It also needs follow-up study to ascertain exact cause-effect relationship.
| Conclusion|| |
We found low-to-moderate QTc abnormality, qualitative more than quantitative, in T2D having poor glycaemic control and very low ECG LVH, which were not significantly affected by disease duration but with male gender and poor glycaemic control. It suggests possible beneficial effect of use of co-existing preventive pharmacotherapy other than hypoglycaemics and a possibility of preventing cardiac repolarisation abnormality with early diagnoses and prompt glycaemic control.
We are thankful to medicine department of our teaching government hospital for allowing us to conduct this study. We kindly acknowledge the support of Indian Council of Medical Research for selecting, approving and funding this project under short-term studentship programme for the year 2015.
Financial support and sponsorship
This study was financially supported by ICMR (Indian Council Of Medical Research) under STS 2015.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]