WJCD  Vol.10 No.10 , October 2020
Evaluation of Sub Clinical Myocardial Systolic Dysfunction Using 2D Global Longitudinal Strain Assessment in Type 2 Diabetes Patients in Sub-Saharan Africa
Abstract: Background: Heart failure is the commonest cardiovascular complication in type 2 diabetes mellitus. However, subclinical left ventricular dysfunction can’t be detected using 2D echocardiography which is routinely used for cardiac evaluation of diabetic patients. We aimed to determine the prevalence and factors associated to left ventricular global longitudinal strain (LV GLS) impairment in type 2 diabetes Cameroonians patients. Methods: We conducted a cross-sectional study from January 2019 to June 2019, including type 2 diabetes patients with preserved left ventricle ejection fraction. Clinical and echocardiographic data were collected, and LV GLS was assessed using speckle tracking technique, a value ≤ -16% been considered as normal value. Results: We recruited 95 patients, with a mean age of 57.4 ± 11.8 years old and median diabetes duration of 5 [2 - 12] years. Echocardiographic evaluation found 56.3% of left ventricle remodelling, 51.6% of left ventricle diastolic dysfunction and mean left ventricle ejection of 63.3% ± 6.6%. LV GLS impairment was present in 43.2% (95% CI: 32.6 - 53.7) of the participants. After adjustment to all significantly associated factors, Obesity (aOR: 4; 95% CI: 1.5 - 10.6) and diastolic dysfunction (aOR: 3.1; 95% CI: 1.2 - 8.2) were independent factors associated with LV GLS. Conclusions: Subclinical systolic dysfunction assessed by LV GLS impairment is frequent in diabetic patients. Further research should be carried out more extensively to integrate LV GLS in the type 2 diabetes patients’ routine follow up for a better prognostic outcome, especially in low-incomes countries.

1. Introduction

Type 2 diabetes is the pathology susceptible to lead to multi organ dysfunction including the heart failure (HF) [1]. Ischemic cardiopathy, diabetic cardiomyopathy and cardiac autonomic neuropathy are the three pathophysiologic mechanisms leading to cardiac complications in diabetes [2]. Diabetic cardiomyopathy is defined as the occurrence of ventricular dysfunction in a diabetic patient and in the absence of coronary atherosclerosis or hypertension [3]. Underlying mechanisms include: altered coronary micro circulation, mitochondrial dysfunction and lipotoxicity [4] [5]. All these complications can lead to left ventricular systolic dysfunction in diabetic patients, which is found in 18% of these patients [6].

Two-dimensional (2D) echocardiography is the leading non-invasive method used routinely for cardiac imaging. However, it cannot detect early ventricular abnormalities, especially when there are no left ventricular (LV) wall motion abnormalities and no reduction in left ventricular ejection fraction. During recent years, speckle tracking echocardiography has been used to assess the global longitudinal strain (GLS) of left ventricle, to detect subclinical systolic dysfunction. Furthermore, impaired GLS is an independent predictor of adverse cardiovascular events like myocardial infarction, heart failure hospitalisations, stroke and cardiovascular mortality [7]. In addition, LV longitudinal myocardial systolic dysfunction has been shown to be the first marker of a preclinical form of diabetic cardiomyopathy in diabetic patients with preserved left ventricular ejection fraction (LVEF) without overt HF [8]. We aimed to evaluate the prevalence and factors associated to impaired LV GLS in a population of diabetic patients from a low-income country where speckle tracking echocardiography is not routinely available.

2. Methods

2.1. Study Design

We conducted a cross sectional study over a period of 6 months (January 2019 to June 2019) at Yaoundé Central Hospital, based on a consecutive sampling, included patients with type 2 diabetes mellitus (DM) and a preserved LVEF who came for outpatient consultation. Informed consent was obtained before inclusion and patients with heart failure, important mitral or aortic valvulopathy, uncontrolled hypertension, atrial fibrillation, or flutter, congenital cardiopathy, anaemia or thyroid dysfunction were excluded from the study. Ethical clearance was obtained from the institutional review board of the faculty of medicine and biomedical sciences of the University of Yaoundé and administrative authorization from the hospital’s directors.

2.2. Clinical Data

Clinical assessment on admission included sociodemographic characteristics, cardiovascular risk factors, and global cardiovascular risk assessment based on the WHO/ISH cardiovascular risk prediction charts for AFR D zone [9].

2.3. Echocardiography

A resting transthoracic echocardiography was carried out using an echocardiogram of brand Philips IE 33. We measured the size of the left ventricle and wall thickness in TM mode during diastole and systole using the parasternal long axis view. This enabled us to calculate the left ventricular mass. LVEF was measured using biplane disc summation method (modified Simpson’s rule) obtained from apical views [10]. Diastolic dysfunction was defined as the presence of at least 50% of these criteria: 1) E/E’ > 14; 2) septal E’ velocity < 7 cm/s or Lateral E’ velocity < 10 cm/s; 3) peak tricuspid regurgitation velocity > 2.8 m/s; 4) indexed left atrial volume > 34 ml/m2 [11]. LVGLS was assessed using speckle tracking technique by evaluating the displacement of the endocardial border, epicardial border and myocardial midline on a 2D image [12]. From data of previous literature, we defined Normal LV GLS as ≤ −16% [13].

2.4. Statistical Analysis

Data were collected using a predesigned structured form and entered in a data entry application conceived in CsPro 7.3. Analysis was carried out using IBM SPSS Version 25. Continuous variable was described using mean ± standard deviation for normally distributed variables and Median [interquartile range] for the other quantitative parameters, while qualitative data were described with frequency and percentage. Comparisons between patient with impaired LV GLS and those with normal LV GLS were performed with t tests for normally distributed continuous variables, U MannWhitney test for non-normally distributed variables, and Chi square tests for categorical variables. Independently associated factors were identified using a multivariate logistic regression analysis including all significantly associated factors on bivariate analysis. Probability values of p < 0.05 were considered statistically significant.

3. Results

3.1. General Characteristics of the Study Population

A total of 95 participants with a mean age of 57.4 ± 11.8 years were included. Females represent 62.1% and hypertension was the leading cardiovascular risk factor found in 56.8%. Table 1 summarise other characteristics of the study population.

3.2. Prevalence of LV GLS Impairment and Associated Factors

As shown in Table 2, 43.2% (95% CI: 32.6 - 53.7) of DM patients with preserved LVEF had LV GLS impairment. The mean LV GLS and LVEF were respectively −17.1% ± 3.2% and 63.3% ± 6.6%. Diastolic dysfunction was found in 49 (51.6%) patients.

Obesity and hypertension were more frequent in the group with impaired LV GLS compared to the group with normal LV GLS, with respectively 53.7% and 22.2% of participants for obesity (p = 0.002), and 70.7% and 46.3% for hypertension (p = 0.017). Diastolic dysfunction was also significantly associated to LV GLS impairment (OR: 3.4; 95% CI: 1.4 - 7.9). Patients with impaired LV GLS had a longer duration of DM compare to those with normal LV GLS (p = 0.047), the median values (IQR) of this duration were respectively 9 (3 - 15) years and 5 (1 - 10) years. After multivariate analysis, obesity (aOR: 4; 95% CI: 1.5 - 10.6) and diastolic dysfunction (aOR: 3.1; 95% CI: 1.2 - 8.2) were independently associated to LV GLS impairment, as shown in Table 3.

4. Discussion

The mean age of the participants was 57.4 ± 11.8 years. Apart from diabetes and obesity, other risk factors present were hypertension and dyslipidaemia. Because of these, more than half of our sample had at least a moderate global cardiovascular risk. The association type 2 diabetes and hypertension were found in 56.8%

Table 1. Characteristics of the study population.

DM: Diabetes mellitus.

Table 2. Echocardiographic characteristics of the study population.

cLVH: concentric Left Ventricular Hypertrophy; LV: Left Ventricular; GLS: Global Longitudinal Strain; LVEF: Left Ventricular Ejection Fraction.

Table 3. Factors associated with impaired LV GLS.

*(Median [IQR]); £Adjusted for age, obesity, hypertension, DM duration, diastolic dysfunction, NA: Not applicable.

of our study participants. A high prevalence of hypertension in patients with type 2 diabetes has been described in many studies, with a prevalence 2 to 3 times greater than in the general population [14]. This association significantly increases the cardiovascular risk through a synergistic effect, multiplying the risk by 4 in women and by 2 in men [15] [16].

A low proportion of our patients had left atrial dilation (5.3%), with a mean indexed left atrial volume of 21.6 ± 6.4 ml/m2. Type 2 diabetes is not recognized as a risk factor for left atrial dilation since many studies failed to find an association between these two variables [17] [18]. We found left ventricular diastolic dysfunction in 51.6% of our participants. Diastolic dysfunction is a risk factor of heart failure with preserved ejection fraction [19] [20]. this occurs due to insulin resistance and metabolic syndrome which induce left ventricular remodelling and lead to diabetic cardiomyopathy. Diastolic dysfunction is highly associated with type 2 diabetes reaching proportions up to 60% compared to 16% in the general population [21].

Fourthy-three patients (43.2%) had a subclinical left ventricular myocardial dysfunction by alteration of the GLS. Ng et al. found a quasi-similar proportion of 44.8% in a similar study [22]. Wang et al. found a proportion of altered GLS of 50% in a similar study in patients with type 2 diabetes and preserved ejection fraction [23]. This finding can be explained by many underlying pathophysiologic mechanisms such as lipotoxicity, glucotoxicity, glycation of proteins, and altered coronary microcirculation [24] [25]. An altered GLS is also known to be an independent predictive factor of adverse cardiovascular events such as heart failure [22] [23] [26].

Obesity was significantly associated with LV GLS impairment. Conte et al. had the same conclusion after observing a significant difference in the mean GLS between obese and non-obese individuals [27]. This association is thought to result from insulin resistance and myocardial steatosis, leading to lipotoxicity and neuro endocrine system activation [24] [27].

Study Limitations

The cross-sectional design used does not enable us to describe the natural history and onset of the sub clinical myocardial dysfunction in our sample. The possible existence of asymptomatic and silent coronary diseases can be a confounding factor in our study.

5. Conclusion

The evaluation the left ventricular contractile function by assessing the Global Longitudinal Strain using 2D speckle tracking echocardiography is important to identify subclinical changes in myocardial function. An important proportion (43%) of the participants in our study—type 2 diabetes patients with preserved ejection fraction—had an impaired LV GLS. Factors independently associated with abnormal myocardial function are obesity and left ventricular diastolic dysfunction. Further research is needed in our context to find additional factors associated with subclinical impaired left ventricular function. We also need to determine the short- and long-term prognosis of these patients and identify therapeutic measures to improve patient outcomes.

Authors’ Contribution

APM: Concept/design, Data analysis/interpretation, Critical revision of article, Approval of article;

CNNG: Concept/design, Data analysis/interpretation, Drafting article, Critical revision of article, Approval of article;

LV: Data collection, data analysis/interpretation, critical revision of article, approval of article;

AJA: Data collection, data analysis/interpretation, critical revision of article, Approval of article;

GSW: Statistics, drafting article, critical revision of article, Approval of article;

DPTN: Statistics, drafting article, critical revision of article, Approval of article;

FN: Data collection, critical revision of article, Approval of article;

HB: Critical revision of article, Approval of article;

SK: Concept/design, Critical revision of article, Approval of article.

Cite this paper: Menanga, A. , Nganou-Gnindjio, C. , Viché, L. , Ahinaga, A. , Ngowa, F. , Wafeu, G. , Njeunje, D. , Bâ, H. , Kingue, S. , (2020) Evaluation of Sub Clinical Myocardial Systolic Dysfunction Using 2D Global Longitudinal Strain Assessment in Type 2 Diabetes Patients in Sub-Saharan Africa. World Journal of Cardiovascular Diseases, 10, 707-715. doi: 10.4236/wjcd.2020.1010068.

[1]   American Diabetes Association (2010) Standards of Medical Care in Diabetes—2010. Diabetes Care, 33, S11-S161.

[2]   Chanudet, X., Chenilleau, M.-C., Schiano, P. and Bauduceau, B. (2008) Insuffisance coronaire, cardiomyopathie et neuropathie autonome chez le diabétique. EMC (Elsevier Masson SAS, Paris), Endocrinologie-Nutrition, 10-366-J-20.

[3]   Poornima, I.G., Parikh, P. and Shannon, R.P. (2006) Diabetic Cardiomyopathy: The Search for a Unifying Hypothesis. Circulation Research, 98, 596-605.

[4]   Haffner, S.M. (2003) Insulin-Resistance, Inflammation, and the Prediabetic State. American Journal of Cardiology, 92, 18J-26J.

[5]   Dagres, N., Saller, B., Haude, M., et al. (2004) Insulin Sensitivity and Coronary Vasoreactivity: Insulin Sensitivity Relates to Adenosine-Stimulated Coronary Flow Response in Human Subjects. Clinical Endocrinology (Oxf), 61, 724-731.

[6]   The Queen of Hearts Consortium, Bouthoorn, S., Gohar, A., et al. (2018) Prevalence of Left Ventricular Systolic Dysfunction and Heart Failure with Reduced Ejection Fraction in Men and Women with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Cardiovascular Diabetology, 17, Article No. 58.

[7]   Liu, J.-H., et al. (2016) Incremental Prognostic Value of Global Longitudinal Strain in Patients with Type 2 Diabetes Mellitus. Cardiovascular Diabetology, 15, 22.

[8]   Ernande, L., Bergerot, C., Rietzschel, E.R., et al. (2011) Diastolic Dysfunction in Patients with Type 2 Diabetes Mellitus: Is It Really the First Marker of Diabetic Cardiomyopathy? Journal of the American Society of Echocardiography, 24, 1268-1275.e1.

[9]   Mendis, S., Puska, P. and Norrving, B. (2011) Global Atlas on Cardiovascular Disease Prevention and Control. World Health Organization, Geneva.

[10]   Lang, R.M., et al. (2015) Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 28, 1-39.e14.

[11]   Nagueh, S.F., Smiseth, O.A., Appleton, C.P., et al. (2016) Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 29, 277-314.

[12]   Voigt, J.-U., et al. (2015) Definitions for a Common Standard for 2D Speckle Tracking Echocardiograhy: Consensus Document of the EACVI/ASE/Industry Task Force to Standardize Deformation Imaging. European Heart Journal—Cardiovascular Imaging, 16, 1-11.

[13]   Yingchoncharoen, T., Agarwal, S., Popovic, Z.B., et al. (2013) Normal Ranges of Left Ventricular Strain: A Meta-Analysis. Journal of the American Society of Echocardiography, 26, 185-191.

[14]   Choukem, S.P., Kengne, A.P., Dehayem, Y.M., et al. (2007) Hypertension in People with Diabetes in Sub-Saharan Africa: Revealing the Hidden Face of the Iceberg. Diabetes Research and Clinical Practice, 77, 293-299.

[15]   Deedwania, P.C. (2000) Hypertension and Diabetes. New Therapeutic Options. Archives of Internal Medicine, 160, 1585.

[16]   Jandeleit-Dahm, K. and Cooper, M.E. (2000) Hypertension, and Diabetes. Current Opinion in Nephrology and Hypertension, 11, 221-228.

[17]   Armstrong, A.C., Gidding, S.S., Colangelo, L.A., et al. (2014) Association of Early Adult Modifiable Cardiovascular Risk Factors with Left Atrial Size over a 20-Year Follow-Up Period: The CARDIA Study. BMJ Open, 4, e004001.

[18]   TODAY Study Group (2015) Alterations in Left Ventricular, Left Atrial, and Right Ventricular Structure and Function to Cardiovascular Risk Factors in Adolescents with Type 2 Diabetes Participating in the TODAY Clinical Trial: Cardiac Structure and Function in TODAY. Pediatr Diabetes, 16, 39-47.

[19]   Wang, M., Yip, G., Wanf, A., et al. (2003) Peak Early Diastolic Mitral Annulus Velocity by Tissue Doppler Imaging Adds Independent and Incremental Prognostic Value. Journal of the American College of Cardiology, 43, 820-826.

[20]   Exiara, T., Konstantis, A. and Papazoglou, L. (2010) Left Ventricular Diastolic Dysfunction in Diabetes Mellitus Type 2. Journal of Hypertension, 28, 294.

[21]   Bell, D.S. (2003) Diabetic Cardiomyopathy. Diabetes Care, 26, 2949-2951.

[22]   von Bibra, H., Thrainsdottir, I.S., Hansen, A., et al. (2005) Tissue Doppler Imaging for the Detection and Quantitation of Myocardial Dysfunction in Patients with Type 2 Diabetes Mellitus: A Methodological Study. Diabetes and Vascular Disease Research, 2, 483-487.

[23]   Ng, A.C.T., Bertini, M., Ewe, S.H., et al. (2019) Defining Subclinical Myocardial Dysfunction and Implications for Patients with Diabetes Mellitus and Preserved Ejection Fraction. American Journal of Cardiology, 124, 892-898.

[24]   Wang, Y., Yang, H., Nolan, M., et al. (2017) Incremental Value of Global Longitudinal Strain in Predicting Heart Failure in Patients with Type 2 Diabetes Mellitus. Heart Lung and Circulation, 26, s137.

[25]   Gulsin, G.S., Athithan, L. and McCann, G.P. (2019) Diabetic Cardiomyopathy: Prevalence, Determinants, and Potential Treatments. Therapeutic Advances in Endocrinology and Metabolism, 10, 1-21.

[26]   Ernande, L. and Derumeaux, G. (2012) Diabetic Cardiomyopathy: Myth or Reality? Archives of Cardiovascular Diseases, 105, 218-225.

[27]   Jorgensen, P.G., Biering-Sorensen, T., Mogelvang, R., et al. (2018) Predictive Value of Echocardiography in Type 2 Diabetes. European Heart Journal—Cardiovascular Imaging, 20, 687-693.