Al-Azhar Assiut Medical Journal

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 17  |  Issue : 2  |  Page : 119--131

Assessment of left ventricular functions by strain and strain rate echocardiography in asymptomatic type II diabetic patients


Mohamed Mahmoud 
 Cardiology Department, Al-Azhar University, Assiut, Egypt

Correspondence Address:
Mohamed Mahmoud
MD of Cardiovascular Diseases Al-azhar University Assiut and Head of Cardiology Department, Cardiology Department, Al-Azhar University, Assiut, 71111
Egypt

Abstract

Background and aim The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eye, kidneys, heart and blood vessels, as treatment to reverse this disorder is more likely to be effective at an early (preclinical) stage, defining the mechanism of diabetic cardiomyopathy may be important to its selective treatment. Aim To assess the left ventricle (LV) function using tissue Doppler (TD) strain and strain rate imaging to detect early LV functions affection in type II diabetic patients without overt heart disease. Patients and methods The study included 60 persons presented in Al Azhar University (Asyut branch) Hospital in the period between November 2014 and January 2016. Were divided into two groups: group (1): 30 diabetic patients with normal (ejection fraction) EF and normal coronaries, group (2): 30 individual without diabetes mellitus (DM) with normal EF as a control group. The following was done for the two groups: 1. Complete History taking and complete general and cardiac clinical examination, resting 12 leads electrocardiography (ECG). 2. Laboratory investigation to diagnose diabetes and the control of the disease. 3. Transthoracic echo examination: 4. TD Strain and strain rate of the LV. Results In comparison between group (1) and group (2) the LV strain and strain rate was found to be significantly lower in group (1) as compared to group (2). Among group I, duration of DM was significantly correlated with decreased strain rate in posterior septum only. There was no correlation between methods of control and the degree of control and the impairment of strain and strain rate. From the present study we found that left ventricular strain and strain rate by conventional echo could reveal the presence of subclinical diabetic cardiomyopathy. Conclusions Type 2 DM deteriorates both LV systolic and diastolic performance. Diabetic patients showed some changes in strain and SR of LV walls at rest especially when the duration of diabetes increased. Strain and SR by TD is superior to conventional Doppler in early detection and evaluation of systolic and diastolic dysfunction in type 2 diabetic patients.



How to cite this article:
Mahmoud M. Assessment of left ventricular functions by strain and strain rate echocardiography in asymptomatic type II diabetic patients.Al-Azhar Assiut Med J 2019;17:119-131


How to cite this URL:
Mahmoud M. Assessment of left ventricular functions by strain and strain rate echocardiography in asymptomatic type II diabetic patients. Al-Azhar Assiut Med J [serial online] 2019 [cited 2020 Apr 7 ];17:119-131
Available from: http://www.azmj.eg.net/text.asp?2019/17/2/119/269759


Full Text



 Introduction



The term diabetes mellitus (DM) describes a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The long-term effects of DM include progressive development of retinopathy, nephropathy, and/or neuropathy, and features of autonomic dysfunction. People with diabetes are at an increased risk of cardiovascular, peripheral vascular, and cerebrovascular disease [1]. A number of experimental, pathologic, and epidemiologic studies support the existence of diabetic cardiomyopathy [2]. The clinical diagnosis of which is made when systolic and diastolic left ventricular (LV) dysfunction are present in diabetic patients without any other known cardiac disease [3]. As with other conditions where new cardiac imaging technologies have identified subclinical heart disease [4], myocardial backscatter and strain characteristics in patients with DM have been shown to be abnormal [5]. As treatment to reverse this disorder is more likely to be effective at an early (preclinical) stage, defining the mechanism of diabetic cardiomyopathy may be important to its selective treatment. However, the etiologic agent for diabetic heart disease remains undefined − the most likely contributors being disturbances of cardiac muscle, pathology involving the cardiac stroma (e.g. fibrosis), or disease of the small vessels [6]. Diabetes upregulates the rennin–angiotensin system, which may contribute to the development of a dilated cardiomyopathy, whereas, locally, angiotensin II may lead to oxidative damage, activating cardiac cell death. These advances in the basic understanding of cellular mechanisms underlying diabetic cardiomyopathy might be relevant to therapy. Tight glycemic control could be a strategy to prevent cardiomyopathy, along with other pharmacologic treatment − for instance, angiotensin-converting enzyme inhibitors, selective blockers of angiotensin II type 1 receptors, or aldosterone antagonists at low nondiuretic doses [7]. In Doppler echocardiographic studies with analysis of combined mitral and pulmonary venous flow and flow during the Valsalva maneuver [8], abnormal LV diastolic filling was demonstrated to be present in ∼50% of normotensive patients with type II DM with normal systolic function. However, LV systolic function is often described in terms of LV ejection fraction (EF) or fractional shortening, reflecting global and radial shortening of the LV, whereas the longitudinal systolic contraction of the outer and inner layer of the myocardium contributes less in these parameters. Tissue Doppler imaging (TDI) has been introduced as a new method of quantifying segmental and global LV function by measuring systolic and diastolic tissue velocities. A derivative of TDI is strain rate (SR) imaging which is a new method for detection of segmental myocardial contraction or stretching [9].

 Aim



The aim of this study is to assess the LV function using tissue Doppler strain and SR imaging to detect early LV function affection in type II diabetic patients without overt heart disease.

 Patients and methods



This study was conducted on 30 type II diabetic patients who presented to the echo lab of Al-Azhar University Hospitals, Assiut, in the period from November 2014 to January 2016 for the evaluation of myocardial performance and exclusion of concomitant coronary artery diseases. This cohort of patients was classified into the study group or group I. The study also included 30 consecutive ages matched nondiabetic persons and was nominated the control group or group II. Inclusion criteria: all included patients were: (a) Nonischemic as defined by normal resting ECG and negative stress ECG test. (b) Having normal EF in the resting echocardiographic (echo) study EF more than 50%. Exclusion criteria: Patients with the following conditions were excluded from the study: (a) LV systolic dysfunction EF less than 50%. (b) Clinical manifestations of congestive heart failure (HF). (c) History and/or evidence of ischemic heart disease. (d) Concomitant significant valvular heart disease as evidenced by echocardiography. (e) Concomitant significant tachy or brady arrhythmias as evidenced by history, 12-lead ECG or Holter monitoring. (f) Poor echogenicity.

Methods

All patients in the study were subjected to the following:

Written consent

A written consent was taken from all patients and controls.

History taking

Thorough history taking with special emphasis on symptoms of ischemia or HF and the presence of risk factors such as smoking, dyslipidemia, hypertension, presence of DM, its duration, and method of control.

Physical examination

All patients underwent thorough physical examination including the following (a) General examination: It was done with special emphasis on signs associated with HF and the measurement of pulse and blood pressure. Patients were considered to be hypertensive when systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg on diabetic patients [10]. (b) Local cardiac examination: To detect the presence of murmurs to exclude valvular heart disease.

Laboratory investigations

Diagnosis of DM and its control: Defined as fasting blood glucose level of at least 126 mg/dl or 2 h postprandial or random sugar more than 200 mg/dl on 2 or more repeated samples, with HbA1c more than 6.5 g%. Poor glycemic control was considered if HbA1c was more than 7 g% [11].Diagnosis of dyslipidemia: It was recognized after obtaining a full lipid profile for all patients. Dyslipidemic patients showed a serum low density lipoprotein (LDL) level of at least 100 mg% according to NCEP-ATP III [12].

ECG

All patients had a baseline 12-lead surface ECG performed. The ECG was examined for ischemic changes as Q waves, ST-T wave changes, heart rate, and rhythm.

Transthoracic echocardiography

Using a GE Vingmed vivid 7 echo machine with a 2.5-MHz phased array probe, acquiring three apical views (apical four-chamber, two-chamber, and long-axis views) in gray scale and color tissue Doppler modes. Mitral inflow velocities were recorded by using conventional pulsed wave. Doppler echo is performed in the usual manner. All images were saved digitally in raw-data format to a magnetooptical disk for offline analysis. LV diameters and wall thicknesses were measured by M-mode echo, using the criteria of the American Society of Echocardiography [12]. Fractional shortening was calculated using the standard formula [13], and LV mass was determined by Devereux’s formula [14]. LV hypertrophy was defined as an LV mass index (g/m2) of more than 131 g/m2 in men and more than 100 g/m2 in women [15]. Resting LV end-diastolic and end-systolic volumes and EF were computed using a modified Simpson’s biplane method. Each representative value was obtained from the average of three measurements.

Strain and strain rate data analysis

Tissue velocity curves were obtained from color TDIs using standard commercial software (Echopac; GE Vingmed, Chicago, Illinois, USA). Peak myocardial early diastolic velocity (Em) and peak myocardial late diastolic velocity (Am) and their ratio were obtained by placing a tissue Doppler sample volume at the lateral annulus in the apical four-chamber view ([Figure 1][Figure 2][Figure 3]).{Figure 1}{Figure 2}{Figure 3}

Statistical analysis

Data were analyzed on an IBM-compatible computer using statistic package of the social sciences version 17 (SPSS, IBM SPSS Inc, Chicago USA). Categorical data were expressed by frequencies and percentages, while continuous data were expressed as mean±SD. χ2-Test or Fisher’s exact test were used to compare categorical data, while unpaired Student’s t-test was used to compare continuous data. Pearson’s correlation coefficient was used to correlate continuous variables. Results were considered significant if ‘P’ value was less than 0.05 and was considered highly significant if P value less than 0.01.

 Results



The study included 60 patients with normal EF and no evidence of coronary artery disease (CAD) as evidenced by normal resting ECG and negative stress ECG test, recruited at the echo lab of Al-Azhar University Hospital, Assuit within the period between November 2014 and January 2016. According to the presence of type II DM, the patients were divided into two groups: group I included 30 patients with DM and group II (control group) included 30 patients without DM. Baseline characteristics of the whole cohort: The mean age of the whole cohort was 54.38±7.71 years (range: 34–71 years). Thirty-one (51.67%) patients were men. Twenty-eight (46.67%) patients were hypertensive and 22 (36.67%) were smokers. Dyslipidemia was found in 26 (43.33%) patients.

The two studied groups were compared as regards age, sex, and risk factors for CAD. There was no statistically significant difference between them as shown in [Table 1].{Table 1}

Echo and TDI findings: the data of transthoracic echocardiography of both groups were compared that showed no statistically significant differences between both groups as regards LV internal diameters, EF by M-mode and modified Simpson’s biplane method, peak myocardial early diastolic velocity (Em), and peak myocardial late diastolic velocity (Am) as shown in [Table 2].{Table 2}

Strain and SR at different walls of the left ventricle among the two groups were compared. These data are shown in [Table 3] and [Table 4].{Table 3}{Table 4}

Strain in the anterior wall and the anterior septum were significantly lower in group I than in group II (P=0.006 and 0.017, respectively), while no significant differences were found between strain in the anterior wall and the anterior septum were significantly lower in group I than in group II (P=0.006 and 0.017, respectively), while no significant differences were found between the two groups as regards strain values in other LV walls ([Figure 4] and [Figure 5]).{Figure 4}{Figure 5}

As regards SR, group I had significantly lower values regarding the anterior wall (P=0.003), inferior wall (P=0.049), posterior wall (P<0.001), and anterior septum (P=0.005), and posterior septum (P=0.023). There was no significant difference between the two groups as regards SR at the lateral wall ([Figure 6][Figure 7][Figure 8]).{Figure 6}{Figure 7}{Figure 8}

Among group I, the mean duration of DM was 6.6±5.99 years (range: 1–28 years). Mean HbA1c was 6.16±1.33% (range: 4.8–10.2%). Sixteen (53.3%) patients were on oral hypoglycemic agents, 13 (43.3%) patients were on insulin, and one (3.4%) patient was on diet control as shown in [Table 5].{Table 5}

Glycemic control was inadequate (HbA1c>7%) in five patients, while 25 patients were controlled (HbA1c<7%). Comparison between the two subgroups regarding strain and SR parameters did not show any significant differences ([Table 6]).{Table 6}

Among group I, the duration of DM was significantly correlated with decreased SR in posterior septum only (P=0.023). On the other hand, there were no significant correlations between duration of DM and strain or SR in other walls ([Figure 9]).{Figure 9}

Selected cases

[Figure 10][Figure 11][Figure 12][Figure 13][Figure 14][Figure 15][Figure 16][Figure 17] represent some patients of this study.{Figure 10}{Figure 11}{Figure 12}{Figure 13}{Figure 14}{Figure 15}{Figure 16}{Figure 17}

 Discussion



Diabetic heart disease had two major components; the first is physiological adaptation to metabolic changes, whereas the second represents degenerative changes. There are many factors such as treatment, metabolic characteristics, lipid profile, and other individual differences that may affect the development of diabetic heart disease, and not all diabetic patients are affected by the same factors or to the same degree. This may result in marked variability in clinical manifestations of diabetic heart disease including subclinical impaired myocardial contractility [19]. DM is considered a major contributor of the development of HF despite the absence of CAD and hypertension even in patients with preserved LVEF. This condition is known as diabetic cardiomyopathy [20]. The pathogenesis of diabetic cardiomyopathy is likely to be multifactorial, including microvascular disease, altered myocardial metabolism, and structural changes in the myocardium with increased fibrosis. Increasingly, evidence is emerging on the role of myocardial lipotoxic injury from lipid oversupply. Visceral adipose tissue insulin resistance leads to increased myocardial fatty acid delivery and uptake with associated myocardial triglyceride accumulation [21]. It has been assumed that the subsequent accumulation of fatty acid intermediates is associated with mitochondrial dysfunction, leading to cell damage, apoptosis, replacement with fibrosis, and myocardial contractile dysfunction [22]. A number of plausible explanations have been proposed to account for reduced myocardial contractility in diabetes. Chronic abnormalities in myocardial carbohydrate and lipid metabolism due to insulin deficiency may result in reduced adenosine triphosphatase activity, decreased ability of the sarcoplasmic reticulum to take up calcium [23], and an intracellular accumulation of toxic fatty acid intermediates [24]. These in turn may lead to adenosine triphosphate depletion, changes in calcium homeostasis, and increased myocardial oxygen consumption. This may produce a focal, progressive loss of myofibrils, transverse tubules and sarcoplasmic reticulum, and separation of the fasciae adherents at the intercalated disk within the myocytes causing myocyte hypertrophy, loss and replacement of fibrosis, and resulting in deleterious effects on myocardial contractility [25]. Early detection and evaluation of the severity of this impairment could lead to an earlier application of preventive measures to delay or avoid the occurrence of clinical heart disease [26]. TDI was introduced as a new method of quantifying segmental and global LV function by measuring systolic and diastolic tissue velocities. Derivatives of TDI are strain and SR imaging which are new methods for detection of segmental myocardial contraction or stretching [27]. In this study, strain and SR were found to be significantly lower in diabetic patients. This finding is concordant with the results of the study of Sertaç Alpaydın et al. [28] who evaluated regional LV myocardial functions by strain and SR echo on patients with type II DM without microvascular complications The study included 40 DM patients (20 women, 20 men; mean age 52.4±7.9 years) without microvascular complications, and 40 healthy controls (20 women, 20 men; mean age 52.8±10.1 years). Conventional Doppler findings were similar in the patient and control groups. Among TDI variables, only early diastolic mitral annular velocity (Em) was significantly decreased (10±2.9 vs. 11.4±3.2 cm/s, P<0.05), and accordingly, mitral inflow E/Em ratio was significantly increased (7.3±2.5 vs. 6.3±2, P<0.05) in patients with DM. The two groups were similar with respect to systolic strain and SR values, except for apical–lateral strain, mid-anterior strain, basal–anteroseptal strain, apical–anterior SR, and mid-anteroseptal SR (P<0.05, for all). Patients with a DM duration of more than 3 years and receiving medical therapy showed similar changes as the overall patient groups and the results of Fang et al. [6] who found that diabetic patients showed reduced systolic function compared with controls, as evidenced by lower peak strain (P<0.001) and SR (P=0.005). And the results of Andersen et al. [29] who analyzed longitudinal contraction of the left ventricle in normotensive type II DM patients with normal EF. They found that patients with type II DM had a significantly lower tissue tracking score index compared with normal participants (5.8±1.6 mm compared with 7.7±1.1 mm; P<0.001). Mean peak systolic velocity was also significantly lower (4.3±1.5 cm/s compared with 5.4±1.0 cm/s; P<0.001), as well as peak systolic SR (−1.2±0.3/s compared with −1.6±0.4/s; P<0.001). Also, the regional systolic peak SR was significantly lower in patients with DM than in normal participants and it is concordant with the results of our study, we found that SR was significantly impaired in the anterior wall, septal wall, inferior wall, and posterior wall, while strain was significantly impaired in anterior wall and anterior septum wall. Also, the results of Ng et al. [30] analyzed the LV multidirectional strain and SR to detect subtle myocardial dysfunction in 47 asymptomatic, male patients with type 2 DM. They found that diabetic patients had impaired longitudinal but preserved circumferential and radial systolic and diastolic function. DM was an independent predictor for longitudinal strain, systolic SR, and early diastolic SR on multiple linear regression analysis (all P<0.001). Fang et al. [6] showed that diabetic patients without overt heart disease demonstrate evidence of subclinical LV systolic dysfunction and this was attributed to hyperglycemia and insulin resistance which are able to induce functional and structural changes of cardiomyocytes and lead to progressive deterioration of regional and global myocardial dynamics. Among group I, the mean duration of DM was 6.6±5.99 years (range: 1–28 years), duration of DM was significantly correlated with decreased SR in the posterior septum (P=0.023) and it is concordant with the results of Andersen et al. [29], who found that long-term hyperglycemia could be part of the cause. Among group mean HbA1c was 6.16±1.33% (range: 4.8–10.2%). Sixteen (53.3%) patients were on oral hypoglycemic agents, 13 (43.3%) patients were on insulin, and one (3.4%) patient was on diet control. Glycemic control was inadequate (HbA1c>7%) in five patients, while 25 patients were controlled (HbA1c<7%). Comparison between the two subgroups regarding strain and SR parameters did not show any significant differences.

 Conclusion



Type 2 DM deteriorates both LV systolic and diastolic performance. Diabetic patients showed some changes in strain and SR of LV walls at rest especially when the duration of diabetes increased. Strain and SR by TDI is superior to conventional Doppler in early detection and evaluation of systolic and diastolic dysfunction in type 2 diabetic patients. Strain and SR of LV walls at rest by conventional echo may be a useful technique to identify subclinical diabetic cardiomyopathy. It seems that the method of control or degree of control has no effect on the development of subclinical cardiomyopathy.

Recommendations

The follow-up study of diabetic patients should be carried out to detect early complications especially subclinical diabetic cardiomyopathy. Large-scale researchers should be carried out to find out the incidence of subclinical cardiomyopathy, factors affecting its development. TDI and strain and SR in association with the conventional Echo study should be implemented to evaluate segmental LV function as a screen test.

Study limitation

The study has certain limitations: (a) the few numbers of patients; (b) single-center study; (c) no follow-up was done for these patients to detect the occurrence of clinical diabetic cardiomyopathy; (d) Most of the patients whether diabetic or hypertensive was on medications which may affect systolic and diastolic functions; (e) to define normal systolic and diastolic myocardial velocities is to some extent difficult because age-dependent variations have not permitted a universally accepted normal value to be defined.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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