Left ventricular diastolic dysfunction may be due to impairment of its systolic or diastolic function or both. Simply stated systolic dysfunction can be considered as defect in the ability of the myofibrils to shorten against a load; thus, the left ventricle reduces or loses it ability to eject blood into the high-pressure aorta. The term diastolic dysfunction implies that the ventricle can not accept blood at its usual low pressure; ventricular filling is slow, delayed or incomplete unless atrial pressure increases. Consequently, pulmonary and/or systemic venous congestion develops. Thus the sign and symptoms of pulmonary and/or systemic venous congestion are not only result of systolic dysfunction rather they are also related to alteration in the diastolic properties of LV chamber (Gaasch et al, 1994). Diastolic dysfunction of the left ventricle is caused by conditions that alter the LV diastolic pressure-volume relation, which in turn leads to an impaired capacity to fill. It may exist with little or no systolic dysfunction. In its mildest form, diastolic dysfunction may manifest only as a slow or delayed pattern of relaxation and filling, with normal or only mild elevation of LV diastolic pressure. In other patients, LV filling may be sufficiently impaired to cause a substantial rise in left atrial pressure. Under these circumstances, diastolic dysfunction may manifest as overt congestive heart failure even in the presence of normal or nearly normal systolic function (Gaasch et al, 1994). Diastolic dysfunction is related by at least two distinct yet interrelated properties of heart, the passive elastic properties and active relaxation of the myocardium. With the loss of elastic properties of the heart, there is reduction in compliance and with impairment of relaxation, there is an increase in myocardial wall tension during diastole, both of which cause increases pulmonary venous pressure (Paul et al, 1996). Intracellular calcium is a critically important determinant of normal myocardial contraction and relaxation. In the myocardial cell the coupling mechanism of excitation-contraction-relaxation are highly dependent on the release of calcium into the cytosol and its receptors within sarcoplasmic reticulum (SR). In clinical syndrome in which diastolic heart failure is a prominent component, abnormalities in the functioning of calcium within the cell have been documented. Beginning with an action potential that initiates myocardial contraction there is an influx of calcium across the cell membrane into the myocardial cell. The calcium at this increased concentration interacts with the regulatory protein of the myofilaments and allows cross-bridge attachments to form between actin and myosin filaments. For contraction to recess, myocardial relaxation must take place and the ability to relax is in turn dependant on reestablishment of low cytosolic calcium concentration. This process in which calcium shifts out of the cytoplasm is critically dependent on SR calcium transporting ATPase. Clearly these mechanisms require energy and support the hypothesis that myocardial relaxation is largely an active process. Abnormalities in the functioning of calcium have been documented in a variety of clinical situations associated with diastolic dysfunction (Walsh, 1994). Coronary artery disease, hypertensive heart disease, aging are all associated with diastolic LV dysfunction (Spencer, 1997). In type 2 DM without known cardiac disease abnormalities of left ventricular mechanical function have been demonstrated in 40-50% of subjects and it is primarily as diastolic dysfunction (Shehadeh A; Regan TJ.). Cellular changes including defects in calcium transport and fatty acid metabolism, may lead to myocellular hypertrophy and myocardial fibrosis initieally causing diastolic dysfunction that may advance to systolic dysfunction (Bell DS, 1995). The existence of a diabetic cardiomyopathy was proposed on the experience on diabetic patients with congestive heart failure in the absence of discernible coronary, valvular, congenital, hypertensive and other known disease (Spector-KS, 1998).
Abnormalities of diastolic filling and relaxation have been observed in-patients with coronary artery disease and have been shown to improve after angioplasty and coronary artery bypass surgery (Bonow, 1982; Goresan, 1994). Myocardial ischemia and infarction leads to diastolic dysfunction at the cellular level through abnormalities in the handling of calcium ions. After the cellular contraction, the reestablishment of a low cytosolic calcium concentration depends on the sequestration of calcium into the sarcoplasmic reticulum by sarcoplasmic reticulum calcium ATPase, a process requiring energy. This process is impaired by myocardial hypoxia and appears even before the inhibition of the energy requiring process responsible for contraction (Aroesty et al., 1985). Cargil et al., (1995) demonstrated that hypoxaemia also appears to impair relaxation of normal ventricles, probably mediated through abnormal calcium transport. Diastolic dysfunction, which occurs in acute myocardial infarction, happens in this mechanism. In chronic myocardial infarction in addition to hypoxia there is ventricular remodeling and ventricular scaring. Both of these cause diastolic dysfunction (Gaasch et al., 1994). To assess LV function both systolic and diastolic function must be determined. This can be accompanied by echocardiography, radionuclide angiography or radiographic ventriculography. Echocardiography appears greatly advantages because of its portability, safety, reproducibility and reliability. Ideally the diagnosis of diastolic dysfunction should be confirmed by documenting elevation of left ventricular diastolic pressure by cardiac catheterization, but this is often impractical. Therefore, non-invasive procedures such as echocardiographic and radionuclide studies are widely used. While radionuclide angiography is a powerful test for excluding left ventricular systolic dysfunction, its use for diagnosing diastolic dysfunction is limited (Spencer 1997). Doppler echocardiography, a non-invasive and simple procedure provides insight into left ventricular diastolic dysfunction (Appleton et al., 1993, Pai et al., 1996). The most commonly used Doppler parameters of diastolic dysfunction are derived from left ventricular inflow and pulmonary venous inflow. A pulsed-wave (PW) Doppler sample volume is placed at the mitral valve leaflets tips to calculate transmitral E and E wave velocities, E/A ratio, deceleration rate (DT) of E wave and duration of A (Ad) wave. In PW Doppler study of pulmonary vein inflow estimates S and D wave velocities, duration of AR (ARd) wave and ratio of Ad to ARd. Alteration of these flow patterns occurs in case of elevation of LV diastolic and LA pressure (Klein et al., 1991). Heart disease is a major health problem throughout the world including Bangladesh. National mortality from heart related disease is 8%, which is the second commonest cause of death in our country next to diarrhea(11%)[Bangladesh Bureau of Statistics, 1999]. Among the heart diseases ischemic heart disease (IHD) is to be mentioned first. According to WHO, it is the number one killer in developed countries and emerging as a serious health problem in developing countries, including Bangladesh (Zaman, 1996). With the improvement of socioeconomic condition, gradual control of infectious diseases, IHD is becoming the major health problem in Bangladesh. Incidence of IHD was 3 per thousand in 1975 (Malik et al., 1976). A study in 1985, demonstrated that the incidence of IHD is 14 per thousand (Malik et al., 1985). Prevalence of IHD in urban population of Bangladesh was reported 100 per thousand (Mahmud et al., 1996). In another survey, it was found that IHD accounts for about 18% of cardiac admission in a general hospital (Latif and Shaha, 1998). Myocardial infarction (MI) is the leading cause of death in Bangladesh, mostly in the 4th decade of life (Khandoker et al., 1986). Mortality AMI is 40 percent (untreated) and 50 percent of them die within the first two hours of the onset of AMI (Amanullah, 1994). The recent report of World Health Organisation (WHO) on diabetes prevalence alarmed that diabetes has posed a serious threat to entire population of the world irrespective of stages of industrialization and development. The increasing prevalence of diabetes mellitus for South East Asian Region (SEAR), was estimated from prevalence in 1995 (About 25 millions) that projected to 30 millions in 2000 and about 78 millions in 2005. This trend observed two folds increase in the developed and almost three folds in the developing nations. Global comparison estimated that highest increase would be observed in SEAR and in Eastern Mediterranean region (East-Med). Of the total global burden of diabetic patients in 2025, more than twenty percent will be found only in the SEAR. Diabetes registry in BIRDEM, a referral center, showed an increasing trend. Only 389 diabetic subjects were registered throughout the year 1960. This figure increased to 181, 2363, 9641 and 17163 in the year 1970, ’80, ’90 and 2000, respectively. This increasing frequency of registration appears to be either increasing awareness of diabetes among people or real increase in diabetes prevalence in the community. Some small diabetes surveys, at community level in different period, proved an increasing prevalence of diabetes and impaired glucose tolerance. Myocardial ischemia can depress cellular concentration of high-energy phosphates. As a result, the energy requiring process of calcium uptake/reuptake by the sarcoplasmic reticulum is impaired and relaxation may be slowed, incomplete and inhomogeneous. The ischemic myocardium becomes less distensable and the LV filling pressure rises (Grossman W, 1985). Thus, the increase in LV filling pressure that occurs during angina pectoris is caused at based partly by regionally impaired myocardial relaxation and a complex interaction between the ischemic and non-ischemic segments. Acute myocardial infarction (AMI) is one of the manifestations of croronary artery disease. In MI there is ischemic necrosis of a variable amount of myocardial tissue as a result of an abrupt decrease in coronary blood flow or an equivalent abrupt increase in myocardial demand for oxygen that can not be supplied by an obstructed coronary artery (Cheitlin et al., 1993). Type 2 DM is characterized by three pathophysiologic abnormalities: impaired insulin secretion, peripheral insulin resistance, and excessive hepatic glucose production. Obesity particularly visceral or central is very common in type 2 DM. Syndrome X is a term used to describe a constellation of metabolic derangement that includes insulin resistance, hypertension, dyslipidemia, central or visceral obesity, endothelial dysfunction, and accelerated cardiovascular disease. Epidemiological evidence supports hyperinsulinemia as a marker for coronary artery disease risk, though an etiologic role has not been demonstrated (Power AC 2001). Collagen accumulation decreasing myocardial compliance, accumulation of advanced glycosylation end product-modified extracellular matrix proteins leads to diastolic dysfunction. Abnormalities in myocardial calcium handling may also contribute to abnormal cardiac mechanics in the diabetic heart. Insulin-dependent diabetes impairs sarcoplasmic reticular ca 2+ pump activities, which reduces the rate of calcium removal from the cytoplasm in diastole. Such alterations may contribute to the increased diastolic stiffness that characterizes diabetic cardiomyopathy. Diabetes related changes in troponin T, the contractile regulatory protein of the thin myofilament, may also contribute to both diastolic and systolic dysfunction. In addition, activation of protein kinase C (PKC) may contribute to cardiac hypertrophy and failure. In addition, a possible major cause of or contributor to chronic left ventricular dysfunction (cardiomyopathy) may be the direct effects of hyperglycemia and insulin resistance on myocardial cellular metabolism. The unavailability of glucose as an energy substrate and the shift in intracellular metabolism from glycolysis to free fatty acid
oxidation can result in inadequate ATP generation and increased production of oxygen free radicals, both of which lead to decreased contractile function (Nesto RW, Libby P 2001). Diastolic dysfunction may manifest as overt congestive heart failure even in the presence of normal or nearly normal systolic function. Diastolic dysfunction is related by at least two distinct et interrelated properties of heart, the passive elastic properties and active relaxation of the myocardium. With the loss of elastic properties of the heart, there is reduction in compliance and with impairment of relaxation; there is an increase in myocardial wall tension during diastole, both of which cause increases pulmonary venous pressure (Paul et al., 1996). With proper management, the prognosis is generally more favourable than in systolic dysfunction. Distinguishing diastolic from systolic dysfunction is essential since optimal therapy for one condition may aggravate the other. Type 2 Diabetes Mellitus (DM) is itself a risk factor of Ischemic Heart Disease (IHD) and independently responsible for diastolic Left Ventricular dysfunction. Type 2 DM and IHD (chronic stable angina) are both chronic disease and result in LVDD. A number of studies regarding diastolic dysfunction in type 2 DM and in chronic stable angina were done in abroad. Till date, no works has been done nor are any data available in our country regarding diastolic dysfunction in type 2 DM and chronic stable angina. With this background present prospective study, entitled “Comparative study on Left Ventricular Diastolic Dysfunction (LVDD) between diabetic patients without angina and Control (Non-diabetic without angina)” by Doppler echocardiography has been undertaken.
MATERIALS & METHODS
This study was a prospective cross-sectional clinical trial conducted in the department of cardiology, Bangabandhu Sheikh Mujib Medical University (BSMMU) and BIRDEM Hospital, Shahbagh, Dhaka from July 2002 to June 2003. For this study diabetic patient (Type 2 Diabetes Mellitus) enlisted in BIRDEM were taken as study subject. On the basis of history, symptoms and investigations (Blood sugar, ECG & ETT) all the patients included in this study were divided into two groups- Group 1: Type 2 Diabetes Mellitus who are on diet control or hypoglycemic agent of age group from 21 to 65 years of age and Group 2: Type 2 Diabetes Mellitus with chronic stable angina (diagnosed on history, ECG and ETT evidence of ischemia) of same age group. In control group the patients are those having no diabetes mellitus and no features of chronic stable angina of same age group and sex. Informed consents were taken from all patients included in this study. Detailed history and clinical examination findings were recorded in predesigned proforma. ECG, Chest X-ray, ETT, Blood sugar and lipid profile were analyzed and also documented. Echocardiography including Doppler with color flow imaging study was done. Coronary angiography (CAG) was not done due to its limitation to diagnose chronic stable angina in type 2 Diabetes Mellitus.
Diabetic patients enlisted in BIRDEM at least more than 6 months with or without chronic stable angina.
Exclusion criteria: a) Subjects with echocardiographic evidence of left ventricular hypertrophy. b) Patients with valvular heart disease c) Presence of congenital heart disease d) Hypertensive heart disease e) Elderly patients more than 65 years f) Patients with myocardial infarction (Q/Non-Q) g) Any pericardial, myocardial or endocardial disease h) Patients with atrial fibrillation i) Left ventricular systolic dysfunction j) Poor echo window, which limits adequate echocardiographic study.
Echocardiography machine which were used for the study had conventional (2D and M-mode) with Doppler and color flow imaging facility. At BSMMU it was ALOKA color Doppler SSD-1000, Japan; at BIRDEM it was Hewlet Packard color Doppler HP IMAGE POINT HX USA. Every center the system was equipped with 2.5 and 3.5 MHz transducers. All patients first underwent M-mode, 2D-echocardiography and were analyzed for chamber enlargement, ventricular hypertrophy and ventricular systolic function. Careful attention was paid to valvular, congenital or pericardial pathology. Special emphasize was given on wall movement. Wall motion abnormalities were graded from normal to dyskinetic motion. LV systolic functions were also graded from mild to severe as per ejection. Mild, moderate and severe grades were <41-60, 35-40% and <35% ejection fraction (EF) respectively (Gersh et al.; 1997). Doppler examination was performed with the subjects in the left lateral dicubitus position. Each wave was evaluated by the pulsed-wave and continuous wave Doppler echocardiography followed by color flow mapping. Same techniques were applied for diagnosing any congenital shunt anomaly. Main emphasize was given on different Doppler parameters related with LV diastolic function. The apical four-chamber view was used to assess the transmitral flow parameter, pulsed Doppler sample volume was placed on the tips of mitral valve leaflets, whereas sample volume was placed 1-2 cm deep in right upper pulmonary vein for assessment of pulmonary venous inflow (Fig. 4). Flow patterns across the mitral inflow i.e., E and A wave velocities, E/A ratio, deceleration time(DT) or E wave, isovolumic relaxation time (IVRT), duration of A wave (Ad) were measured. Similarly flow patterns across the pulmonary inflow i.e. S and D wave velocities, S/D ratio, atrial reversal (AR) and duration of AR (ARd) were measured. Ad/ARd ratio was calculated (Fig. 5 & 7). Normal values for the Doppler parameter were already mentioned (p48). As per the values of transmitral and pulmonary venous inflow parameters, different types/grades of diastolic dysfunction were classified. They were absent, abnormal relaxation, pseudonormalization and restrictive patterns. All Doppler values were recorded. Flow spectral was also printed on polaroid paper with a printer.
The numerical data obtained from the study were analyzed and significance of difference was estimated by using the statistical methods. Data were expressed in frequency, percentage, mean and standard deviation as applicable. Comparison between groups was done by standard “t” test, chi-squared test, and ‘F’ test (ANOVA) as applicable. All data were analyzed by using computer based SPSS program. Probability less than 0.05 were considered as significant.
In this study, 154 patients were taken randomly after excluding all exclusion factors. All patients were categorized into three different groups; diabetes without angina, diabetes with chronic stable angina (CSA) and control (Non-diabetic without angina) group. Samples were taken nearly equal in all three groups and were compared with each other. Out of 154 patients, 51 (33.12%) were in Diabetic without angina group, 53 (34.41%) were in Diabetic with chronic stable angina (CSA) group and 50(32.47%) patients were in control group (Non-diabetic without angina). The age distribution of the population ranged from 21-65 years. The mean age of diabetes without angina, diabetes with chronic stable angina (CSA) and control group was 50.8 ± 8.61, 52.19 ± 9.32 and 48.6 ± 9.49 respectively. In the age group 21-30 the age distribution was slightly significant but in the other age group it was not significant. The sex distribution showed that the total number of female patients in the population was 77 (50%). In diabetes without angina group male patients were relatively lower (39.22% Vs. 60.78%) and male patients were relatively more (62.26% Vs. 37.74%) in diabetes with CSA group. Among 154 patients only 18(11.69%) had complain of shortness of breath (SOB) but the rest of 136 subjects had no complain of SOB. The P value(>0.05) showed SOB variation was not significant among the three different study subjects. Out of 53 patients with the history of diabetes associated angina, most of the patients (83.02%) were with angina at that time and the rest 9(16.98%) patients had no symptoms of angina during echocardiography. The mean arterial blood pressures were 95.82 ± 3.84, 94.83 ± 3.60 and 94.18 ± 3.18 in diabetes without angina, diabetes with CSA and control group respectively. The P value (>0.05) indicated that the effect of mean arterial blood pressure was not significant. Most of the sample subjects (about 62..26%) from diabetic with angina group(53) had no abnormal ECG changes. Among the 53 subjects of diabetes mellitus associated with angina about 18.87% (10) shows positive ETT. Again this study group out of 53 subjects of diabetes with CSA group, 29(54.72%) have taken antianginal drug and the reest 24(45.28%) have not taken antianginal drug. LA internal diameter pattern figure out that most of the subjects (131) had left atrial (LA) internal diameter less than 40 mm and 23 subjects had greater than or equal to 40 mg left atrial internal diameter. LA internal diameter increased in case of diabetic condition and further increased slightly in case of diabetes associated with angina patients. If was observed that total average LVIDs in male (34± 27.94) wa higher than that of in female (26.96±6.63). The average LVIDs was found in male of diabetes without angina group (46.64±53.07). The average LVIDd was higher in diabetes with CSA group (45.74±5.45) comparing with control (44.10±5.62) and diabetes without angina group (43.33±10.74). Again the average LVIDd of female subjects were slightly higher than that of the male subjects. In study subjects of diabetes without angina group possess a remarkable number of subjects with abnormal LV wall motion. LV wall motion abnormalities is seen in a significant number of sample subjects (18 out of 53) of diabetes with CSA group. In control group (Non-diabetic without angina) left ventricular wall motion was almost normal for maximum sample subjects. Ejection fraction (EF) percentage had negligible difference among the three sample subjects group. In diabetes without angina group the different parameters of mitral and pulmonary flow varied from mild to moderate. Some subjects in this group, had E/A ratio, deceleration time (DT) and IVRT value out of the specified range (24,20 and 22subjects respectively). In diabetes with CSA group the different parameters of mitral and pulmonary flow varied from mild to moderate. Some subjects in this group had E/A ratio, DT and IVRT value out of the specified range (30, 27 and 27 patients respectively). Some patients had higher peak AR (5) than the normal range (<35). In control group the different parameters of mitral and pulmonary flow was almost within the normal limit. Some subjects in control group had IVRT value out of the specified range (60-100 m sec). In control group 11(22%) had delayed relaxation and the rest 39(78%) was normal. Among DM without angina and DM with angina group all the three different stages of LVDD were present with delayed relaxation having more frequently. Among various age group out of the total study subjects of 154, 6(3.9%) subjects of age group 21-30 had no diastolic dysfunction. The diastolic dysfunction increased with the age and showed more prevalence at the age range of 51-60 years (22.73%) of total diastolic dysfunction of 47.40%). Among 154 study subjects 77(50%) was male an 77(50%) was female. In female group, 43 (27.92%) was normal and the rest 34(22.08%) subjects had diastolic dysfunction. On the other hand in male group, 38(24.68%) was normal and the rest 39(25.32%) subjects had diastolic dysfunction. Among 51 sample subjects 23(45.0%) subjects of diabetes without angina group had no LVDD and 28(54.9%) subjects had different stages of LVDD. On the other hand, among 50 sample subjects of control group, 39(78%) subjects had no LVDD and 11(22%) subjects were found with different stages of LVDD. P value (<0.001) obtained from chi-square analysis indicated that the LVDD was significantly higher in subjects having diabetes mellitus without angina than control (Non-diabetic without angina).
Among the sample subjects of 104, diabetes without angina group had 51 (49.0%) subjects and diabetes with CSA had 53(51.0%) subjects. In diabetes without angina group, 23 (22.1%) subjects had no diastolic dysfunction and the rest 28(26.9%) subjects had different stages of diastolic dysfunction with more prevalence of delayed relaxation. And in diabetes with CSA group, 19(18.3%) subjects had no diastolic dysfunction and the rest 34(32.7%) subjects had different stages of diastolic dysfunction having more prevalence of delayed relaxation 28(26.9%) stage. P value (>0.10) reached from Chi-square analysis showed that the prevalence of diastolic dysfunction was not statistically significant in two groups.
Recently there has been increasing knowledge and interest regarding the contribution of diastolic dysfunction in producing signs and symptoms of cardiovascular disorders. Abnormal diastolic function is increasingly appreciated as a major contributor to cardiac morbidity and mortality. Diastolic dysfunction has been observed in the presence or absence of systolic dysfunction. The advent of Doppler echocardiographic study has provided a rapid, repeatable, non-invasive method by which left ventricular diastolic function is assessed (De Maria et al., 1991). Accurate non-invasive assessment is crucial to the broad application and understanding of this common condition. Echocardiographic parameters have become the backbone of this non-invasive assessment (Steve R. Ommen, 2001). The increase incidence of congestive heart failure and the increased mortality and morbidity in the diabetic patients following myocardial infarction (MI) or coronary artery bypass graft (CABG) can be explained by the presence of diabetic cardiomyopathy. Non –invasive studies in young diabetic patients show no cardiac abnormality, but in older diabetic patients mild cardiac diastolic dysfunction is detectable. This mild cardiomyopathy can become clinically detectable in the presence of hypertension and can be severe in the presence of myocardial ischemia. In Bangladesh no study data has yet been available regarding the frequency, type and outcome of LV diastolic dysfunction in type 2 diabetes mellitus with chronic angina (CSA). In the current study an attempt was made to compare data of various study with that from the present study. In this study, various grades of diastolic dysfunctions were evaluated in type 2 diabetic patient with or without chronic stable angina and these were also compared with non diabetic age and sex matched control subjects. A total of 154 patient were evaluated by Doppler study, among which 51(33.12%) wre diabetes without angina, 53 (34.41%) were diabetes with CSA and rest 50(33.47%) were non diabetic without angina (Control group). On the basis of history, symptoms and investigations (Blood sugar, ECG and ETT) all the patients included in this study were divided into two study groups: 1) type 2 diabetes mellitus who were on diet control or hypoglycemic agent. 2) type 2 diabetes mellitus with CSA (diagnosed on history, ECG and ETT evidence of ischemia).
Age is nonmodifiable risk factor ischemic heart disease. Increasing age is associated with increasing incidence of atherosclerotic coronary disease. Diabetes mellitus is also a risk factor of ischemic heart disease. So elderly diabetic patient is more vulnerable for ischemic heart disease. The age range of the present study was from 21 to 65 years. Among the study population mean age was 50.8± 8.61, 52.19±9.32 and 48.6±9.41 in sample subjects of diabetes without angina, diabetes with CSA and control group respectively. Other than patient aged 21-30 years, there was no significant difference of age in different group. Among the study subjects of 154, 6(3.9%) subjects of age group 21-30 had no diastolic dysfunction. The diastolic dysfunction increased with the age and showed more prevalence at the range of 51-60 years (22.73% of total population) which corresponds to the study of diastolic dysfunction in elderly by Kitzman, DW. Diastolic left ventricular function was altered substantially with advancing age in healthy persons, and diastolic dysfunction impacted most cardiovascular disorder in the elderly. In this study, it was shown that most heart failure in the elderly occurred in presence of preserved systolic function (presumed diastolic heart failure).
Male sex is independent risk factor for ischemic heart disease. Females before menopause are less likely to have an ischemic heart disease (chronic stable angina) than male. Among the distribution of sex, total number of female patients in the population was 77(50%). In all over the world, almost all of the study reported an overwhelming majority of male patients. In diabetes without angina group male patients were relatively lower (39.22% vs 60.78%) and male patients were relatively more (62.26% vs 37.74%) in diabetes with CSA group, which indicated the prevalence of IHD in male was more. Out of 77(50%) female patient 43(27.92%) was normal and the rest 34(22.08%) was normal and the rest 39(25.32%) subjects had diastolic dysfunction. Here diastolic dysfunction was slightly more in male subjects, which had no statistical significance. In this study group of 154 patients only 18(11.69%) were symptomatic and complained of SOB on exertion. Only 3 subjects complained of SOB on rest. Most of the symptomatic patients were in study group, which was not statistically significant between study and control group. Presentation of LV diastolic dysfunction also depends upon the type of severity of dysfunction. By means of Doppler mitral flow along with pulmonary venous flow velocity, three abnormal patterns had been identified indicating progressively greater impairment of diastolic function. In the delayed relaxation stage many of these patients, were asymptomatic. In pseudonormal stage, most patients had complained of exertional dyspnoea (SOB). In restrictive pattern of LVDD patients were markedly symptomatic and demonstrated a severely reduced functional capacity (Little W C, 2001). In our study most of the patients had diastolic dysfunction in delayed relaxation stage and had 11.69% SOB. Among the patients of diabetes with CSA group, 10(18.87%) patients complained of chest pain during echocardiography and 29(54.72%) were taking antianginal drug, 20 (37.74%) had ECG changes and 10(18.87%) showed positive ETT. In our study acute myocardial infarction and unstable angina (acute coronary syndrome) were excluded. Only chronic stable angina (IHD) was included in this study. Chronic stable angina can be diagnosed by history of characteristic chest pain and evidence of any ischemia (ECG evidence of ischemia, echocardiographic evidence of ischemia and ETT evidence of ischemia). Ischemic heart disease is the commonest cause of heart failure frequently associated with left ventricular systolic dysfunction. Although some patients particularly the elderly have diastolic dysfunction (Pezzano, -A). Hypertension is one of the important causes of diastolic dysfunction in all over the world. Close association was also found between hypertension and diastolic dysfunction of left ventricle in Bangladesh population (Rahman, 1997; Rahman M, 1999). Hypertension is itself important risk factor of ischemic heart disease. The development of diastolic dysfunction in the hypertensive heart disease is the combined end result of increased wall tension, decreased myocardial collagen content and elevated myocardial ACE activity (Wheeldon et al., 1994). Only normotensive patients were included in this study of which mean arterial blood pressure were 95.82±3.84, 94.83±3.60 and 94.18±3.18, in diabetes without angina, diabetes with CSA and control group respectively, had no statistical significance. Among 154 patients, 23 patients had left atrial internal diameter ≥mm, which was more common in study group than control group. In delayed relaxation stage of diastolic dysfunction, vigorous atrial contraction compensates for the reduced early filling due to impaired left ventricular relaxation while maintaining normal mean left trial pressure and left atrial internal diametr will be normal. In pseudonormal stage left atrial and left ventricular end diastolic pressure are elevated and left atrium is increased in size. In restrictive pattern of LVDD diastolic filling pressure are elevated and left atrium is dilated and hypocontractile (Little w C, 2001). In this study, LVIDd’s and LVIDs’s of study and control group were within normal limit. But some variation in LVIDs between male and female were observed. In our study myocardial infarction (acute/old), cardiomyopathy and valvular heart disease were excluded. So, LV diameters were within normal limit in our study population. Out of 154 subjects, 32(20.78%) had regional wall motion abnormalities (RWMA), which was more common in diabetes with CSA group. Ischemic heart disease was diagnosed echocardiographically by observing RWMA. Here RWMA was more common in diabetes with angina, which is consistent with ischemic heart disease. Among the diabetes without angina group 5.84% had hypokinesia with mean EF% of 65.6±6.24% patient of diabetes with CSA group 11.69% had hypokinesia with mean EF% 62.79±9.33% and in control group it was 3.25% and 66.2±5.88% respectively. In our study left ventricular systolic were excluded. Here mean EF% was almost similar in the three study groups. During Doppler echocardiography averages of mitral and pulmonary flow pattern had no characteristic changes among study and control group. But there were some changes in E/A ratio, DT, IVRT and peak AR velocity among the study group. In diabetes without angina group the E/A ratio was out or normal range (1-2) in 24 subjects. There were also some subjects with abnormalities in deceleration time (DT) and IVRT value of the specified range (20 and 22 subjects respectively). On the other hand in diabetes with CSA group, some sample subjects had abnormal E/A ratio, DT and IVRT value out the specified range (30, 27 and 27 subjects respectively). Doppler patterns of diastolic dysfunction include abnormal relaxation, pseudonormal filling and restricted filling. These patterns evolve from one to another in a single individual with changes in disease evaluation, treatment and loading condition as described by Gerald et al., 1996. Abnormal relaxation is typically manifested by E/A ratio <1, increased deceleration time (DT) [>220 m sec] and an increased isovolumic relaxation time (IVRT) [>100 m sec] and an increased isovolumic relaxation time (IVRT)[>100 m sec] with sample volume position at mitral flow. At this stage Doppler pulmonary venous flow parameters usually remain normal. Patient may be mildly symptomatic with exertional activities. In this stage filling pressure is normal having normal LA dimension. Pseudonormalization refers to normal appearance of mitral flow (E/A ratio between 1.0 and 2.0, DT; 150-220 m sec, IVRT: 60-100 m sec), but there is abnormal pulmonary venous flow (S/D ratio < 1, AR velocity > 35cm/sec, Ad/ARd ratio < 1). At pseudonormal stage, the effects of impaired relaxation on early diastolic filling become opposed by the elevated left atrial pressure. For this reason the early diastolic transmitral pressure gradient and mitral flow velocity pattern return to normal. This phenomenon is called pseudonormalization to indicate that although the left ventricular filling appears normal, significant abnormalities of diastolic functions are present. In most cases, left atrial, left ventricular end diastolic filling pressure (LVEDP) are elevated, the left atrium is increased in size and patients often complain of exertional dyspnoea. The restricted filling patterns is characterized by; increased E/A ratio (>2), decreased DT (<150 m sec), decreased IVRT (<60 m sec) on mitral flow, and decreased S/D ratio (<1), increased AR velocity (>35 cm/sec) and decreased Ad/ARd ratio (<1) on pulmonary venous flow. Restrictive state represents a severe decrease in LV chamber compliance. Diastolic filling pressures are elevated and patients are markedly symptomatic and demonstrate a severely reduced functional capacity. The left atrium is dilated and hypocontractile (Little W C, 2001). Among the study subjects, total of 73 patients had diastolic dysfunction of which diabetes mellitus without angina group 24 (47.1%) had delayed relaxation, 3 (5.9%) had pseudonormalization and 1(1.9%) had restrictive f
rom of LVDD. In diabetes mellitus with angina group these were 28(52.8%), 4(7.5%) and 2(3.8%) respectively. Whereas in control group only 11(22.2%) had delayed relaxation type of LVDD. Among patient of diabetes mellitus without angina 28(54.9%) had LVDD whereas it was 11(22%) in control group which was statistically significant. But there was no significant difference of LVDD among diabetic population with or without angina [34(63%) vs. 28(54.9%)]. Dwyer, -E –M et al., studied 233 patients of diabetes, hypertension and obese persons with normal coronary arteries and found 44% had diastolic dysfunction. In our study, 63% LVDD was observed in diabetes with CSA group and that was 54.9% in diabetes without angina group which was nearly similar with the above mentioned study. It was probably due to common mechanism of developing LVDD. Zabalgoitia, M et al., studied 86 normotensive, asymptomatic wit hweel controlled type 2 diabetes mellitus patients for prevalence of diastolic dysfunction. He used traditional transmitral filling patterns for diastolic physiology and Valsalva maneuver was used to differentiate normal form pseudonormal LV filling patterns. Of which 30% had delayed relaxation and 17% had pseudonormal filling pattern which was consistent with our study. Diastolic dysfunction in type 2 diabetes mellitus patients is often found despite adequate metabolic control and freedom from clinically detectable heart disease. Poirier P et al., studied 46 men with type 2 diabetes of age group 38-67 years and LVDD was found in 28 subjects(60%). Of which 32% delayed relaxation and 28% pseudonormal pattern of LVDD. In context of total LVDD result is consistent with our study. In all the recent studies including mine it was shown that LVDD was much more common than previously reported in subjects with well controlled type 2 diabetes who are free of clinically detectable heart disease.
The impact of diastolic dysfunction on cardiac morbidity and mortality is becoming increasing understood and it has become apparent that significant proportions of patients presenting with signs and symptoms of congestive heart failure have primary diastolic dysfunction. Our study was conducted to find out frequency, types of LVDD in type 2 diabetes mellitus without angina or with chronic stable angina (CSA) by Doppler echocardiography. The study was carried out in the department of cardiology, BSMMU and department of cardiology BIRDEM hospital during the period 2002-2003. In this study, samples were taken randomly and were categorized into three different groups, diabetes without angina, diabetes with CSA and control (Non-diabetic without angina) respectively. The samples taken were nearly equal in all three groups. Out of 154 sample subjects 51 (33.12%) were in diabetic without angina group, 53 (34.41%) were in diabetes with CSA group and 50(32.47%) subjects were in control group (Non-diabetic without angina). The age range was 21-65 years with a mean age of 50.8±8.61 and 52.19±9.32 in study subjects of diabetes without angina and diabetes with CSA respectively. In diabetes without angina group male patients were relatively lower (39.22% vs. 60.78%) and male subjects were relatively more (62.26% vs. 37.74%) in diabetes with CSA group, which indicated the prevalence IHD in male was more. Only normotensive patients were included in this study, of which mean arterial blood pressure were 95.82±3.84 and 94.83±3.60 in diabetes without angina and diabetes with CSA group respectively. Out of 53 patients of diabetes with CSA group, 10(18.87%) subjects complained of chest pain during echocardiography. 23 subjects of total 154 sample subjects have left atrial internal diameter ≥ 40 mm, which was more prevalent in study group. 32 (20.78%) subjects of total 154 had regional wall motion abnormalities (RWMA), which was more prominent in diabetes with CSA group. But there was some changes in E/A ratio, DT, IVRT and peak AR velocity among the study group. Among the total LVDD of 73 subjects, 28 (38.36%) subjects were from diabetes without angina group, 34 (46.57%) subjects were from diabetes with CSA group and the rest 11(15.07%) were from control group. In this study, no pseudonormal and restrictive pattern of LVDD was found in control group. Among the diabetic population, different grades of diastolic dysfunction were identical in both angina or without angina group [Delayed relaxation- 28(82%) vs. 24(86%), pseudonormalization- 4(12%) vs. 3(10.7%) and restrictive pattern- 2(6%) vs. 1(3.3%). In comparison of both diabetes without angina and diabetes with CSA, with control group, the LVDD patterns were significantly different. But there was no significant difference of LVDD between diabetic population with or without angina [34(63%) vs. 28(54.9%)].
Left ventricular diastolic dysfunction (LVDD) is present in type 2 diabetes mellitus and also in type 2 diabetes mellitus associated with chronic stable angina. Left ventricular diastolic dysfunction can be diagnosed properly with Doppler echocardiography. In our series, there is significant difference of LVDD between diabetes without angina and control (Non-diabetic without angina) group. Statistically significant difference of LVDD is also observed between diabetes with chronic stable angina (CSA) and control group. But there is no significant difference of LVDD between diabetes without angina and diabetes with CSA. Diabetes mellitus may cause LVDD in similar way as do chronic stable angina. But, both diabetes mellitus and chronic stable angina together do not increase LVDD significantly. There is no synergistic effect on LVDD of these two disease condition together. Distinguishing diastolic from systolic dysfunction is essential since optimal therapy for one condition may aggravate the other. Earlier diagnosis of LVDD and optimum treatment of precipitating factors is very important to prevent congestive heart failure.
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