ORIGINAL ARTICLE JIACM 2002; 3(2): 164-8 Echocardiographic and Doppler Assessment of Cardiac Functions in Patients of Non-Insulin Dependent Diabetes Mellitus Rajesh Rajput*, Jagdish**, SB Siwach***, A Rattan**** Abstract Diabetes mellitus is a chronic progressive metabolic disease. It involves myocardium at a relatively early stage even before clinical manifestation(s) become obvious. The present study was undertaken to assess cardiac functions by echocardiography and doppler in patients of NIDDM before and after control of hyperglycaemia. This study included thirty patients of uncomplicated type-2 diabetes mellitus (duration > 1 year) and thirty, age and sex matched, healthy subjects. Pre-treatment blood sugar, fasting (182.46 ± 33.92 mg%) and post-prandial (245.76 ± 37.87 mg%), was significantly higher than the post-treatment values (101.93 ± 10.17 mg% and 152.75 ± 15.42 mg% respectively). Systolic functions of LV were within normal range in all patients. Diastolic dysfunction of LV was very common and was detected in 63% of patients (A/E > 1.0). None of the control subjects had systolic or diastolic dysfunction. Diastolic dysfunction persisted even after control of hyperglycaemia over three-month duration. It is suggested that all patients of NIDDM should be routinely and repeatedly subjected to 2D-echocardiography and doppler assessment of cardiac functions in long term management of this metabolic disease. Long-term glycaemic control may result in decrease/ reversal of diastolic dysfunction or development of overt cardiomyopathy. Key words Diabetes, Diastolic dysfunction. Introduction * Lecturer ** Professor *** Professor and Head **** Senior Resident Department of Medicine, Pt. BD Sharma PGIMS, Rohtak-1240 001 (Haryana). Diabetes mellitus is associated with a multitude of cardiovascular complications, e.g., increased incidence of atherosclerotic coronary artery disease, myocardial infarction, congestive heart failure, coronary microangiopathy, and systemic arterial hypertension. In addition, structural myocardial involvement termed as diabetic cardiomyopathy may be there which is suggested by clinical, epidemiological, and histological studies done till date in large number of diabetics 1,2. Myocardial involvement in diabetics may occur relatively early in the course of disease, initially impairing early diastolic relaxation and when more extensive, it causes decreased myocardial contraction. Prior to the development of symptomatic congestive heart failure, subclinical left ventricular dysfunction (systolic or diastolic) exists for sometime 3-5. However, frequency of progression from pre-clinical to clinically evident myocardial dysfunction is not established. Further, role of metabolic control in primary prevention or reversal of myocardial dysfunction had not been much studied. With the availability of echocardiography and doppler, it is now possible to fully elucidate the natural history of cardiac involvement from pre-clinical to clinical stage in patients with diabetes 6,7. The present study intends to assess diabetic patients by echocardiographic and doppler parameters, specifically excluding diabetes mellitus with neurological, cardiovascular, pulmonary, and renal complications. Material and methods The study material comprised of sixty subjects. 1. Uncontrolled diabetes mellitus type2 30 subjects duration 1 year (Group A). 2. Normal healthy controls 30 subjects, age and sex matched (Group B).
The patients with history of diabetes mellitus, hypertension, valvular dysfunction, coronary artery disease, significant pulmonary or renal disease, and neurological disease were excluded from the study. Each had normal ECG, chest X-ray, and exercise treadmill test negative for myocardial ischaemia. 24 hours urinary albumin excretion was < 500 mg. Echocardiographic assessment was done in 2 dimensional mode, M-mode, and doppler mode using colour flow mapping. Each patient was examined in left lateral recumbent position using standard parasternal, short axis, and apical views. From the pulsed doppler spectrum of mitral flow, the following measurements were made: (figure 1). 1. Peak velocity of early filling (E) 2. Peak velocity of atrial filling (A) 3. Ratio of A/E 4. Deceleration time-dt (msec) 5. Acceleration time-at (msec) 6. Isovolumetric relaxation time (IVRT) 7. Isovolumetric contraction time (IVCT) From the 2-D echo using apical 4-chamber view, the ejection fraction was calculated using the area-length method. Aortic, pulmonary, and tricuspid valves were studied in detail. Echo and doppler parameters were repeated in patients of diabetes mellitus after control of diabetes. Data so obtained was analysed using student s paired t test, while difference between various Fig. 1 : Showing Doppler Velocites baseline parameters in diabetics and controls was analysed using student s unpaired t test. The p value of > 0.05 was taken as nonsignificant, < 0.05 as probable significant, < 0.01 as definitely significant and < 0.001 as highly significant. Results Baseline characteristics of the study population were comparable. Group-A (Patients) had an average age of 42 ± 4.78 years. Group-B (Control) had an average of 39.6 ± 6.27 years. Male and female ratio was comparable in both the groups (Table I). Blood sugar levels were elevated in all patients, both in fasting samples (182.46 ± 33.92 mg%) as well as in post-prandial samples (245.76 ± 37.87 mg%) at the start of study. After three months of treatment these levels were near normal (fasting 101.93 ± 10.17 mg% and postprandial 152.75 ± 15.42 mg% respectively). The difference in both fasting and post-prandial levels was statistically significant (P < 0.001). Blood sugar levels were within normal limits in all controls. None, patients and controls, had evidence of other systemic disease, which could have potentially affected the heart. A conventional 12 lead ECG in all patients had no abnormality. All patients were subjected to stress test and were found to have normal responses with ST segment, never exceeding 1.0 mm. None of the patients suffered from arrhythmia/chest pain during or after exercise and none showed any hypertensive blood pressure response. Using the doppler study, the atrial filling (A) wave velocity in msec in diabetic patients (0.71 ± 0.18) was found to be significantly higher (p < 0.01) when compared with normal controls (0.59 ± 0.13). The early filling (E) wave velocity in msec in diabetic patients (0.67 ± 0.17) was found to be significantly lower when compared with normal controls (0.79 ± 0.15). Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002 165
The comparison of atrial filling (A) and early filling (E) wave ratios, i.e., A/E, suggestive of diastolic dysfunction was seen in 63% of diabetics. Maximum percentage of patients with diastolic dysfunction (43%) was seen in 41-50 years age group. While no patient had diastolic dysfunction in group B. In diabetics, A/E (1.09 ± 0.26) was found to be statistically significant and higher (p < 0.001) when compared with normal controls (0.74 ± 0.12) and is suggestive of impaired relaxation type of diastolic dysfunction. None of the patients had pseudonormalisation or restrictive filling pattern of diastolic dysfunciton. The mean value of A/E was > 1 in 60% of patients even after correction of hyperglycaemia. Acceleration time (AT) in diabetics (56.66 ± 19.7 msec) was found to be significantly lower when compared with normal controls (69.33 ± 21.76 msec). (13.20 ± 2.40 mm) and 2D-echo parameters like stroke volume (SV) (60.93 ± 21.20 ml/m 2 ), ejection fraction (EF) (59.16 ± 8.31%), and fractional shortening (FS) (29.03 ± 10.24%) were not found to be statistically significant when compared with normal controls (Table II). After three months of treatment, all these echodoppler parameters were not found to be statistically different from pre-treatment values. Discussion The importance of diastolic dysfunction as a cause for heart failure in isolation or associated with systolic dysfunction is increasingly recognised. Three patterns of abnormal diastolic function have been recognised, i.e., impaired relaxation, pseudonormalisation, and restrictive filling 8. Impaired relaxation is characterised by A/E > 1, prolonged IVRT, and increased DT. Pseudonormalisation refers to Table I : Baseline characteristic of study population. Characteristics Patients Controls Number of patients 30 30 Age (years ± SD) 42±4.78 39.6±6.27 Male 15 15 Female 15 15 Pre-treatment fasting blood sugar (mg%) 182.46±33.92 Pre-treatment postprandial blood sugar (mg%) 245.76±37.87 Post-treatment fasting blood sugar (mg%) 101.93±10.17 Post-treatment fasting blood sugar (mg%) 152.75±15.42 However, deceleration time (DT) (181.33 ± 64.97 msec), isovolumetric contraction time (IVCT) (66.0 ± 18.68 msec), isovolumetric relaxation time (IVRT) (120 ± 29.86 msec), and other M-mode parameters like left ventricular end-diastolic dimension (LVEEDD) (45.73 ± 4.93 mm), left ventricular end-systolic dimension (LVESD) (32.16 ± 6.02 mm), left ventricular posterior wall thickness in diastole [LVPW (D)] (9.27 ± 1.60 mm), left ventricular posterior wall thickness in systole [LVPW (S)] normal appearance of ventricular inflow (A/E < 1). This pattern is due to combined effects of abnormal relaxation and elevated LV pressure and is considered as intermediate stage between impaired relaxation and restrictive physiology due to natural progression of disease. Reduction of preload by doing Valsalva manoeuvre can convert pseudonormal pattern to impaired relaxation pattern and thus helps in this abnormality. Restrictive filling pattern is characterised by markedly decreased A/E, short 166 Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002
DT, and reduced IVRT. This pattern is associated with greater LV filling pressures and poor prognosis. Thus, impaired relaxation pattern of early disease progresses to increase in ventricular wall thickness, decrease in ejection fraction and poor prognosis. in normal controls (< 1). This abnormality was seen in 63% of diabetics. Other workers have reported similar results as well 6-8. The mean value of A/E ratio was > 1 in 60% patients even after correction of hyperglycaemia. However, improvement in left ventricular function was noted Table II : Results : 2-D echo and doppler parameters in diabetics and controls. Echo./Doppler Patients Patients Normal p-value p-value Pre-treatment Post-treatment subjects a : c b : c Parameter (a) (b) (c) A-velocity (M/sec.) 0.71 ± 0.18 0.69 ± 0.18 0.59 ± 0.13 < 0.01 < 0.01 E-velocity (M/sec.) 0.67 ± 0.17 0.68 ± 0.19 0.79 ± 0.15 < 0.001 < 0.001 A : E ratio 1.09 ± 0.26 1.07 ± 0.29 0.74 ± 0.12 < 0.001 < 0.001 AT (m sec.) 56.66 ± 19.7 58 ± 5.38 69.33 ± 21.76 < 0.01 < 0.01 DT (m sec.) 181.33 ± 64.79 181 ± 45.51 159 ± 50.19 NS NS EF (%) 59.16 ± 8.31 58.13 ± 6.65 59.63 ± 9.22 NS NS FS (%) 29.03 ± 10.24 29.06 ± 9.2 27.96 ± 8.65 NS NS IVRT (msec) 120 ± 29.86 59.16 ± 8.31 130.33 ± 28.29 NS NS IVCT (msec) 66 ± 18.68 66.33 ± 23.26 67.33 ± 16.59 NS NS Left ventricular diastolic function has been shown to be affected at an early stage in several myocardial diseases when systolic functions remain normal 3,5,6. Left ventricular diastolic filling patterns by doppler correlate closely with those obtained by contrast and radio-nuclide angiographic techniques 7. These velocity-derived indices have proved to be a sensitive indicator of impaired left ventricular filling even in early stages of myocardial diseases. Till the recent past, all importance was being given to systolic functions of the heart. But in the last decade clinicians and researchers have discovered that both reversible and irreversible abnormality of left ventricular diastolic functions contribute significantly to symptoms and morbidity in individuals with a variety of cardiac disorders, including those with normal or near normal systolic function 4-6. It was observed that A/E ratio was significantly abnormal (> 1) in diabetics as compared to value with the correction of hyperglycaemia in 39 percent of patients of type 2 diabetes by Uusitupa et al 9. The difference could primarily be due to the exclusion of patients of myocardial ischaemia by performing exercise treadmill test at the beginning of the present study. Total of 70 percent of patients had deceleration time more than 150 msecs. Left ventricular wall thickness defined as the sum of ventricular septal and posterior wall thickness, relative wall thickness, and LV mass was statistically insignificant both in systole as well as in diastole when compared with normal controls. However, Galderisi et al 1 found an increase in left ventricular wall thickness. This increase could be because of interstitial deposition of para amino-salicylic acid glycoproteins and interstitial fibrosis seen in patients with diabetes mellitus 1. The present study did not show any significant decrease in ejection fraction in diabetics and the Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002 167
results of study correlated well with the study done by Mathew et al 6 in young diabetics where they found no statistical difference in ejection fraction in diabetics and normal controls. From the foregoing discussion, it can be concluded that diastolic dysfunction in patients of NIDDM is present in 60% of patients even when the DM is present at younger age, is of shorter duration, and has no effects on other body systems. This dysfunction persists even after control of diabetes mellitus over a duration of 3 months and it is suggestive of pre-clinical diabetic cardiomyopathy. However, long-term effect of good control of diabetes may result in decrease of this diastolic dysfunction, deceleration of the development of clinical cardiomyopathy, and decreased morbidity and mortality. It is suggested that all patients of NIDDM should be routinely and repeatedly subjected to 2-D colour doppler echocardiographic assessment of cardiac functions in the long-term management of this metabolic disease. This has important therapeutic implications and helps physicians planning early intervention strategies. Thus, diastolic dysfunction can be used as an early indicator, as it is a precursor to increased LV hypertrophy and clinical left ventricular dysfunction. References 1. Galderisi M, Anderson KM, Wilson PWF, Levy D. Echocardiographic evidence for the existence of a distinct cardiomyopathy. Am J Cardiol 1991; 68: 85-9. 2. Panja M, Sarkar C, Kumar S et al. Diabetic cardiomyopathy. JAPI 1998; 46 (7): 635-9. 3. Mittal SR, Bharadwaj A, Gupta VD, Kapoor NC. Noninvasive assessment of pre-clinical left ventricular dysfunction in young diabetics. Ind Heart J 1983; 35 (4): 204-6. 4. Thanikachalam S, Lakshminathan C, Vishwanathan M et al. Sub clinical diabetic cardiomyopathy - Assessment by systolic time intervals. J Assoc Phy Ind 1981; 29: 267-72. 5. Ahmed SS, Jaferi GA, Narang RM, Regan TJ. Pre-clinical abnormality of left ventricular function in diabetes mellitus. Am Heart J 1975; 89 (2): 153-8. 6. Mathew P, John L, Jose J, Krishna Swami S. Assessment of left ventricular diastolic function in young diabetics - A two dimensional echo doppler study. Ind Heart J 1992; 44 (1): 29-32. 7. Studdard MF, Pearson AC, Kun MJ et al. Left ventricular diastolic dysfunction: comparision of pulsed doppler echocardiography and haemodynamic indexes in subjects with and without coronary artery disease. J Am Coll Cardiol 1989; 13: 327-36. 8. Gerald Cohen, Joseph Pietroluhgo, James Thomas. A practical guide to assessment of ventricular diastolic function using doppler echocardiography. J Am Coll Cardiol 1996; 27: 1573-1760. 9. Uusitupa M, Siitonen O, Aso A et al. Effect of correction of hyperglycaemia on left ventricular function in noninsulin dependent (Type II) diabetics. Acta Med Scand 1983; 213: 363-8. 168 Journal, Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002