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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 9  |  Issue : 4  |  Page : 205-210

Exercise electrocardiogram testing in asymptomatic patient with type 2 diabetes and left ventricular diastolic dysfunction


Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Web Publication11-Mar-2020

Correspondence Address:
Dr. Ahmed Shaker
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JICC.JICC_21_19

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  Abstract 


Background: Type 2 diabetes mellitus (DM) is an established risk factor for cardiovascular events and the development of congestive heart failure (HF). Diastolic dysfunction is considered a precursor of HF and may be diagnosed noninvasively by echocardiography. Diastolic dysfunction is common in well-controlled type 2 diabetic patients without clinically detectable heart disease. Left ventricular diastolic dysfunction represents the earliest preclinical dysfunction and that it can progress to asymptomatic HF. Aim of the Work: The aim of the study is to evaluate if diastolic dysfunction in diabetic patients is due to silent ischemia. Methods: This study included 80 asymptomatic patients with type 2 DM. Echocardiography was done to all patients to assess systolic and diastolic functions. Exercise electrocardiogram (ECG) was done for all patients to detect ischemic heart disease. Coronary angiography was done to patients with positive exercise ECG test. Results: The incidence of diastolic dysfunction was 75%; among the studied groups. Impaired relaxation was detected in 87 % and pseudo normal pattern was detected in 13 % of subjects with diastolic dysfunction. Patients with normal diastolic function had negative stress exercise test, while those with diastolic dysfunction, 12 patients had positive exercise stress ECG (40%) and 18 patients had negative exercise stress ECG (60%). Conclusion: These findings indicate that coronary artery disease is not uncommon in diabetic patients with diastolic dysfunction and increase markedly in patients with positive stress exercise electrocardiography.

Keywords: Diabetes mellitus, diastolic dysfunction, exercise electrocardiography


How to cite this article:
Shaker A. Exercise electrocardiogram testing in asymptomatic patient with type 2 diabetes and left ventricular diastolic dysfunction. J Indian coll cardiol 2019;9:205-10

How to cite this URL:
Shaker A. Exercise electrocardiogram testing in asymptomatic patient with type 2 diabetes and left ventricular diastolic dysfunction. J Indian coll cardiol [serial online] 2019 [cited 2020 Apr 6];9:205-10. Available from: http://www.joicc.org/text.asp?2019/9/4/205/280343




  Introduction Top


Diabetes is a risk factor for the development of asymptomatic heart failure (HF), particularly in elderly patients with type 2 diabetes.[1],[2] HF that occurs as a result of impaired myocardial relaxation and compliance has been termed diastolic HF.[3] Diastolic HF develops despite normal left ventricular (LV) systolic contractile function and leads to significant morbidity, medical cost, and mortality. Typically, patients with type 2 diabetes who are symptomatic from diastolic HF have superimposed hypertension, coronary artery disease, LV hypertrophy, atrial fibrillation, or renal insufficiency.[4] Diabetic patients have a higher incidence of congestive HF as compared to age-matched nondiabetic participants. Several causative mechanisms for diabetic cardiomyopathy have been postulated including microangiopathy, autonomic nervous dysfunction, defective cellular calcium transport as well as structural changes in myocardial intracellular proteins, and accumulation of collagen leading to increased stiffness of ventricular wall.[5]

Doppler echocardiography is one of the most useful clinical tools for the assessment of LV diastolic function. Doppler indices of LV filling are used not only for diagnostic purposes but also for establishing prognosis and evaluating the effect of treatment.[6] LV diastolic dysfunction may represent the first stage of diabetic cardiomyopathy reinforcing the importance of the early examination of diastolic function in individual with diabetes.[7] Diabetes is associated with increased cardiovascular complications, the most common of which are ischemic cardiomyopathy and LV dysfunction. Diabetes is also associated with HF, mainly through its association with hypertension and coronary artery disease.[8] Diabetes mellitus (DM) speeds up the process of coronary atherosclerosis and functional and structural cardiac impairments.[9],[10] DM is not only a significant independent risk factor for the development of atherosclerotic ischemic heart disease or ventricular hypertrophy, but it is also able to trigger a diabetic cardiomyopathy due to some metabolic processes: inhibition of switching within the cardiomyocyte from free fatty acid (FFA) to glucose metabolism, dysregulation of FFA metabolism with increased uptake, reduced FFA oxidation, reduction of peroxisome proliferator-activated receptor (PAPAR), increase of PAPAR-g and insulin-resistance, and increased intracellular lipogenesis which leads to cardiomyocyte lipotoxicity.[11] The patients with type 2 DM are at 2–5 folds higher risk for developing HF.[12] Some large trials reported that the prevalence of DM in patients with chronic HF is around 30% and close to 50% in those with acute HF.[13],[14]


  Methods Top


This study included 80 patients with type 2 DM who has normal electrocardiogram (ECG) and normal systolic function. Exclusion criteria were patients with hypertension, congestive HF, valvular heart disease, atrial fibrillation, conduction abnormalities, echocardiographic evidence of LV systolic dysfunction, and patients with contraindications to exercise ECG as (electrolyte abnormalities, resting ECG changes, muscular disorder, acute illness, etc.,). After taking a written consent, all patients underwent complete echo-Doppler study using a commercially available echocardiography machine (Hewlett-Packard 5500 Sons machine imaging system). LV dimensions, left atrial dimensions, wall thickness and ejection fraction were measured. Furthermore, transmitral flow was done by pulsed wave Doppler between the tips of mitral valve leaflets from four-chamber view measure peak E wave velocity, peak A wave velocity, E/A ratio, E wave deceleration time, and isovolumic relaxation time (IVRT). Exercise ECG was done to all patients to detect ischemic heart disease and those with positive exercise ECG will prone to coronary angiography.


  Results Top


The study included 80 asymptomatic patients with type 2 DM. According to the presence of LV diastolic dysfunction on the echo-Doppler study and the results of stress ECG, patients were divided into three groups:

  • Group I: included 36 (14 males and 22 females) diabetic patients with LV diastolic dysfunction with negative stress ECG
  • Group II: included 24 (18 males and 6 females) diabetic patients with LV diastolic dysfunction with positive stress ECG
  • Group III (control group): included 20 (12 males and 8 females) diabetic patients with normal LV diastolic function.


The statistical analysis showed a significantly higher age in Group II (P< 0.03) than the control group and Group I. From odds ratio, the higher age of diabetic patients above 50 years is associated with 1.42-fold increase in the risk of developing LV diastolic dysfunction as shown in [Table 1].
Table 1: Demographic and clinical carachteristics of the study population.

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Regarding the fasting blood sugar level, there was no significant difference between the studied groups (P = 0.06). From odds ratio, the increase in the fasting blood sugar level above 180 mg/dl is associated with 1.2-fold increase in the risk of developing LV diastolic dysfunction.

Regarding the postprandial sugar level, there was one significant difference between the studied groups (P = 0.46). From odds ratio, the increase in postprandial sugar level in diabetic patients above 250 mg/dl is associated with 1.4-fold increase in the risk of diastolic dysfunction as shown in [Table 1].

There was a significant lower duration of diabetes in control group compared to other groups (P< 0.001), from odds ratio, the duration of 2 or more years of diabetes is associated with two-fold increase of the risk of diastolic dysfunction.

There was no statistically significant difference between the three groups regarding to left atrial dimension (P = 0.81), aortic root dimension (P = 0.65), LV end-diastolic dimension (P = 0.15), ejection (P = 0.92), and LV mass (0.98), while there was statistically significant increase in Groups I and II in comparison with control group regarding LV end-systolic dimensions (P = 0.004) and posterior wall thickness (PWT) (P = 0.04) as shown in [Table 2].
Table 2: M-Mode and 2-D echocardiographic data of the study group.

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There was statistically no significant difference among the study groups regarding to mean E wave (P = 0.66), while there was a statistically significant increase of mean A wave in Groups I and II in comparison to control group (P = < 0.001) and also significant increase of mean A wave in Group II in comparison with Group I (P = < 0.001). The statistical analysis shows a significant decrease of mean E/A ratio in Groups I and II in comparison with the control group (P = <0.001) and also a significant decrease of mean E/A ratio in Group II in comparison with Group I (P = <0.001).

The statistical analysis shows no significant difference among the study groups regarding deceleration time of E wave (P = 0.02) while there was a significant increase of IVRT in Groups I and II in comparison to control group (P = <0.001) as shown in [Table 3].
Table 3: Diastolic function indices in the study population.

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In Groups I and II, there were 36 patients with negative stress exercise ECG (60%) and 24 patients with positive stress exercise ECG (40%). While in the control group, there were 20 patients with negative stress exercise ECG (100%). The statistical analysis showed a significant increase in the number of stress exercise ECG-positive patients among diabetic patients with diastolic dysfunction than diabetic patients without diastolic dysfunction (P< 0.001). Regarding function capacity, there was no significant difference among diabetic patients with and without diastolic dysfunction (P = 0.12) as shown in [Table 4].
Table 4: Stress exercise ECG in diabetic patients with versus those without LV diastolic dysfunction.

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Patients with positive stress exercise ECG were subjected to coronary angiography. Among these patients, 8 had normal coronary angiography (33%), 8 had single vessels disease (33%), 4 had two vessel disease (16.7%), and 4 had the three-vessel disease (16.7%) as shown in [Table 5].
Table 5: Result of coronary angiography in group II.

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  Discussion Top


Epidemiological data indicate a greater risk of cardiovascular morbidity and mortality, particularly congestive cardiac failure, in diabetic participants as compared with those without diabetes.[15] The prevalence of DM in the HF population is close to 20% as compared with 4%–6% in control group.[16] Early detection and evaluation of the severity of this impairment lead to an earlier application of preventive measures to delay or avoid the occurrence of clinical heart disease.[7]

In the present study, 80 asymptomatic patients were included in the study. Diastolic dysfunction was detected in 60 (75%) patients, while 20 (25%) of them had normal diastolic function and were taken as control group. Among the 60 patients who had diastolic dysfunction, impaired relaxation was detected in 32 (87%) patients and the pseudonormal pattern was detected in 8 (13%) patients which were unmasked by Valsalva maneuver. The restrictive pattern was not noted in any patients. Poirier et al. attempted to determine the prevalence of LV diastolic dysfunction in asymptomatic participants with type 2 diabetes in a study, which included 46 men who have no evidence of diabetic complications, hypertension, coronary artery disease, congestive cardiac failure, thyroid, or renal disease. LV diastolic dysfunction was found in 28 (60% participants, of whom 7 (15%) had a pseudonormal pattern of ventricular filling and 21 (45%) had impaired relaxation.[7]

In our study, neither age nor glycemic control could be contributing factors in the development of diastolic dysfunction in our patients. However, age >50 years was associated with 1.42-fold increase in the risk of developing diastolic dysfunction, and 2 h postprandial blood glucose level >250 mg/dl was associated with 1.4-fold increase in the risk of developing diastolic dysfunction. The relationship between diastolic dysfunction and glycemic control is still a matter of debate as Poirier et al., Devereux et al., and Shreatha et al. concluded that fasting and 2 h postprandial blood glucose levels did not correlate with the presence of diastolic dysfunction in type 2 diabetes. Those authors claim that the process starts early in the disease.[7],[17],[18] On the other hand, Holzmann et al. have shown a correlation between glycemic control and LV dysfunction with associated improvement in cardiac function after adequate treatment.[19] It is unclear whether glycemic control by any methods alone is the effective intervention or whether insulin and insulin sensitizer medications are a specific requirement for the prevention of diastolic dysfunction.[20]

In our study, we found that the duration of DM is the major contributing factor in the development of diastolic dysfunction, and patients with duration of diabetes <2 years have normal diastolic function. Furthermore, we found that duration of 2 years or more of DM was associated with two-fold increase in the risk of developing diastolic dysfunction. Devereux et al. and Rathod et al. showed that patients with diabetes of more than 2-year had two times higher risk of developing diastolic dysfunction and the longer the duration of diabetes, the higher the incidence, and severity of diastolic dysfunction.[17],[21] DM is associated with increased risk of diastolic dysfunction and diabetic cardiomyopathy due to several factors including microangiopathy, autonomic nervous dysfunction, defecting cellular calcium transport, structural changes in myocardial intracellular proteins, accumulation of collagens leading to increased stiffening of the ventricular wall, deposition of glycoprotein, activation of rennin-angiotensin system, and decreased adiponectin level.[5]

The current study showed a significant increase in LV end-systolic diameter and PWT in patients with diastolic dysfunction than those with normal diastolic function. On the other hand, LV mass was comparable in all patients with and without diastolic dysfunction. Although there was increase in LV mass in all patients with DM, it showed no significant correlation with different diastolic dysfunction indices. Devereux et al. and Ilercil et al. determine that diabetes has been implicated as important determinant of LV mass. Myocardial and systemic mechanisms, as increased extracellular matrix, vascular hypertrophy, and vasoconstriction, have been attributed to this response.[17],[22]

Our study showed that there was a significant increase in mean a wave and IVRT in Groups I and II in comparison with the control group and significant increase in mean a wave and IVRT in Group II in comparison with Group I. Furthermore, there was a significant decrease in mean E/A ratio in Groups I and II in comparison with the control group and also significant decrease in mean E/A ratio in Group II in comparison with Group I. This could be attributed to the variation in glycemic control and the variation in duration of DM among patients in the group population.

The current study showed that aortic sclerosis and mitral annular calcification were comparable among different groups which denote that neither duration of DM nor presence of diastolic dysfunction has a role in their development. Eren et al. stated that aortic stiffness is increased in patients with hypertension, diabetes, or both even after the exclusion of coronary artery disease. Aortic stiffness and LV diastolic dysfunction are also associated in these patients.[23] This contradiction could be explained by small number of patients in our study, absence of other atherosclerosis risk factors in addition to individual response variation as well as age variation.

Our study showed that there was a significant difference between groups in the results of stress exercise electrocardiography. All patients with no diastolic dysfunction were stress exercise electrocardiography negative (100%) while 12 patients of those with diastolic dysfunction (30 patients) were stress exercise electrocardiography positive (40%). This is concordant to the result of Kligfield and Lauer who found that the number of patients with positive stress exercise electrocardiography increases in the presence of diastolic dysfunction caused by any causes mainly DM and hypertension.[24]

Our study showed that there was no significant difference between group studies in the functional capacity. This is discordant to the result of Grewal et al. which stated that abnormalities of diastolic function seemed to be related to a lower exercise capacity and the magnitude of the effect of diastolic abnormalities became greater in older patients. Also stated that exercise improves diastolic function in healthy individuals but its effects on diastolic dysfunction are less clear.[25] This contradiction could be explained by the absence of coexisting other medical diseases that may affect or decrease exercise functional capacity. Also by variation in age, body mass index, and gender of the patients may play a role.

In our study, 8 of 30 patients (24%) with diastolic dysfunction had coronary artery disease evident by coronary angiography. On the other hand, 8 of 12 patients (66.6%) with diastolic dysfunction and positive stress exercise electrocardiography had coronary artery disease evident by coronary angiography. The remaining 4 patients with positive stress exercise electrocardiography had normal epicardial coronary artery; however, small vessels disease may be present. These findings indicate that coronary artery disease is common in diabetic patients with diastolic dysfunction and increase markedly in patients with positive stress exercise electrocardiography. Patients with positive stress exercise electrocardiography and coronary artery disease evident by coronary angiography had a comparable diastolic function index to those with negative stress exercise electrocardiography. This could be explained by the absence of myocardial ischemia at rest and hence its effects on the diastolic function indices.


  Conclusion Top


These findings indicate that coronary artery disease is not uncommon in diabetic patients with diastolic dysfunction and increase markedly in patients with positive stress exercise electrocardiography. Patients with positive stress exercise electrocardiography and coronary artery disease evident by coronary angiography had a comparable diastolic function index to those with negative stress exercise electrocardiography.

Recommendation

  • All diabetic patients even if asymptomatic should be evaluated for the presence of LV diastolic dysfunction by echocardiography, especially after 2 years of diabetes, and the evaluation should include procedure as Valsalva maneuver
  • Presence of LV diastolic dysfunction is indication to start preventive measures for future cardiac events
  • Diabetic patients with diastolic dysfunction should be subjected to stress test evaluation.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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