Clinical and morphological features of human hypertensive-diabetic cardiomyopathy

The existence of a specific cardiomyopathy secondary to diabetes mellitus is controversial. During a 2-year period, we had the opportunity to examine nine diabetic patients at autopsy who had clinically severe congestive heart failure and minimal extramural coronary artery atherosclerosis. Unexpectedly, all nine patients were found to be hypertensive. Accordingly, we initiated a detailed study of the clinical and morphological features of this group, and compared the findings to age-matched autopsied subjects with either isolated hypertension, isolated diabetes mellitus, or no heart disease.The study of the hypertensive-diabetic hearts revealed severe interstitial fibrosis, focal or confluent scars, and extensive myocytolytic activity. Comparison with the diabetic, hypertensive, and normal groups showed statistically significant differences in regard to the degree of interstitial and focal scarring, and the presence of myocytolysis. Only the hypertensive group had minimal interstitial scarring. There were no statistical differences in the small vessel changes between the four groups, although subjectively the hypertensive and hypertensive-diabetic patients had more severe disease.It is concluded that the association of diabetes mellitus and hypertension in the absence of significant coronary artery atherosclerosis may lead to a severe cardiomyopathy. Although the etiology of myocardial failure in this syndrome is uncertain, the degree of myocardial fibrosis and the frequency of myocytolytic lesions possibly related to catecholamine hypersensitivity, are potential explanations. Several studies suggesting that hypertension has adverse consequences in diabetes, as well as an animal model of hypertensive-diabetic cardiomyopathy, support our conclusion that cardiomyopathy associated with diabetes mellitus is a specific entity which may be secondary to the combined effects of diabetes and hypertension on the myocardium.     

A cross-sectional study of echocardiographic indices, treadmill exercise capacity and microvascular complications in Nigerian patients with hypertension associated with diabetes mellitus.

Associations between hypertension and cardiovascular complications of diabetes mellitus in Nigerians, were examined in a cross-sectional study. 20 hypertensive-diabetic patients, 16 hypertensive patients, 10 non-hypertensive diabetic patients and 10 age- and sex-matched healthy controls, underwent M-mode and cross-sectional echocardiography, and Bruce-protocol treadmill exercise performance. Left ventricular (LV) mass indices (+/- SD) were significantly higher in hypertensive patients (164 +/- 12gm-2), diabetic (158 +/- 17gm-2) and hypertensive diabetic patients (125 +/- 129gm-2) compared with normal controls (111 +/- 17gm-2) p < 0.01. However, the LV mass index in the hypertensive-diabetic patients was significantly less than in hypertensive (p < 0.05) or normotensive diabetic patients (p < 0.05). Systolic cardiac contractility measured as fractional fibre shortening, was preserved in the hypertensive patients (24 +/- 4%) compared with the healthy controls (23 +/- 4%), but was depressed in diabetic patients (19 +/- 3%) and to a greater extent in the hypertensive-diabetic patients (15 +/- 4% p < 0.01). Treadmill exercise tolerance time was reduced independently in hypertension (309 +/- 73 seconds) or diabetes (321 +/- 119 seconds), p < 0.05, but was further impaired in hypertensive-diabetic patients (289 +/- 110 seconds) p < 0.01 compared to the healthy controls (490 +/- 156 seconds). The patients with hypertension and diabetes had a greater degree of proteinuria (p < 0.001) and a higher frequency of retinopathy (p < 0.001), in comparison to those with hypertension or diabetes alone.     

Role of atrial natriuretic peptide in congestive heart failure due to chronic diabetes.

OBJECTIVE: It is now believed that diabetes sensitizes the myocardium so that superimposed hypertension with its attendant vascular changes results in progressive myocyte damage leading ultimately to congestive heart failure. In this regard, remarkable progress has been made within the past few years with a family of closely related peptides, the atrial natriuretic peptides (ANPs), which are involved in the regulation of plasma volume. Any changes in their levels and/or action can be seen to participate in the development of diabetes-induced congestive heart failure. While the literature reasonably supports the evidence for a defect in the ANP-receptor coupling system in hypertensive and diabetic animals, it is not as clear that this is the cause for heart failure. The present article attempts to demonstrate evidence for causality. DESIGN: The present article summarizes existing knowledge on the involvement of ANP in the induction of fluid imbalance. In particular, the role of ANP in congestive heart failure, hypertension, diabetes and congestive heart failure in diabetes is examined. Recent data in experimental hypertensive-diabetic rats, obtained from this laboratory have also been described here. MAIN RESULTS: There are now several reports which indicate high plasma ANP concentrations in both patients and animals with heart failure, thus implicating a role for this peptide. The present paper deals with ANP-induced molecular changes in kidney basolateral membranes in congestive heart failure due to chronic diabetes. CONCLUSION: Congestive heart failure in diabetes with hypertension may be due to uncoupling of the ANP-receptor effector system in the kidney basolateral membrane. It is possible that other neurohumoral agents through a wide variety of activities may also contribute to the pathophysiology of this disease.     

Beneficial effects of diltiazem on the natural history of hypertensive diabetic cardiomyopathy in rats.

Hypertensive diabetic rats develop a cardiomyopathy characterized by systolic and diastolic ventricular dysfunction, myocardial hypertrophy and fibrosis, pulmonary congestion and a very high mortality rate. Alterations in contractile proteins and sarcoplasmic reticular calcium (Ca2+) transport in diabetic myocardium and their partial reversal with verapamil suggest that calcium channel blockade may prevent death from congestive heart failure in hypertensive diabetic rats. A large group of rats with renovascular hypertension and streptozotocin diabetes were divided into four groups: untreated animals (Group 1) and animals treated with 100 (Group 2), 300 (Group 3) or 600 (Group 4) mg/kg per day of sustained release diltiazem mixed in their food. Treatment was begun shortly after the onset of hypertension and diabetes. Mortality rates after 4 months were 59% (19 of 32), 53% (17 of 32), 27% (7 of 26) and 35% (12 of 34) in Groups 1, 2, 3 and 4, respectively; the mortality rate in age-matched control rats was 5% (1 of 19). The reductions in mortality rates in Groups 3 and 4 were statistically significant. Diltiazem did not change systolic blood pressure, serum glucose concentration, heart rate or left ventricular mass. There was a trend to decreased left ventricular interstitial fibrosis and perivascular fibrosis in diltiazem-treated animals. Ventricular collagen concentration was similar in untreated hypertensive diabetic and control rats; levels were higher in hypertensive diabetic rats that died than in those that survived. There was a trend to decreased collagen concentration as diltiazem dose increased. Myosin isoenzyme distribution was not changed in Groups 3 and 4 (in comparison with Group 1). In all hypertensive diabetic groups, rats that died had a higher blood pressure, heart rate, relative left ventricular mass, lung weight and lung water than did survivors. The mortality rate was two to three times higher among rats with an initial blood pressure greater than or equal to 180 mm Hg. The beneficial effects of diltiazem on survival were most significant among rats with severe hypertension.     

Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy

The distribution of fibrosis was studied quantitatively in the entire left ventricular wall of a transverse slice of the heart from 10 necropsy cases of hypertrophic cardiomyopathy, 10 cases of hypertensive heart disease, and 20 normal adults. The percentage area (mean (SD)) of fibrosis in the left ventricular wall in hypertrophic cardiomyopathy (10.5 (4.3)%) was significantly greater than that in hypertensive heart disease (2.6 (1.5)%) or in normal hearts (1.1 (0.5)%). In hypertrophic cardiomyopathy the percentage area of fibrosis was greater (13.1 (4.8)%) in the ventricular septum than in the left ventricular free wall (7.7 (4.2)%) whereas in hypertensive heart disease and normal hearts values in these two areas were similar. The percentage area of fibrosis in the left ventricular free wall (where myocardial fibre disarray was not extensive even in hypertrophic cardiomyopathy) was greater in hypertrophic cardiomyopathy than in hypertensive heart disease. The percentage area of fibrosis correlated with heart weight in hypertensive heart disease, but not in hypertrophic cardiomyopathy. These results suggest that widespread fibrosis in hypertrophic cardiomyopathy cannot be explained by cardiac hypertrophy alone, and that disarray and other factors are also important in pathogenesis. The increase in the percentage area of fibrosis from the outer to the inner third of the left ventricular free wall in hypertrophic cardiomyopathy and in hypertension probably reflected transmural gradients of wall stress and myocardial fibre diameter. Although fibrosis is not specific to hypertrophic cardiomyopathy, its quantification and analysis of its regional distribution provide information that is useful in investigating the pathophysiology of the disorder.     

Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy.

The distribution of fibrosis was studied quantitatively in the entire left ventricular wall of a transverse slice of the heart from 10 necropsy cases of hypertrophic cardiomyopathy, 10 cases of hypertensive heart disease, and 20 normal adults. The percentage area (mean (SD)) of fibrosis in the left ventricular wall in hypertrophic cardiomyopathy (10.5 (4.3)%) was significantly greater than that in hypertensive heart disease (2.6 (1.5)%) or in normal hearts (1.1 (0.5)%). In hypertrophic cardiomyopathy the percentage area of fibrosis was greater (13.1 (4.8)%) in the ventricular septum than in the left ventricular free wall (7.7 (4.2)%) whereas in hypertensive heart disease and normal hearts values in these two areas were similar. The percentage area of fibrosis in the left ventricular free wall (where myocardial fibre disarray was not extensive even in hypertrophic cardiomyopathy) was greater in hypertrophic cardiomyopathy than in hypertensive heart disease. The percentage area of fibrosis correlated with heart weight in hypertensive heart disease, but not in hypertrophic cardiomyopathy. These results suggest that widespread fibrosis in hypertrophic cardiomyopathy cannot be explained by cardiac hypertrophy alone, and that disarray and other factors are also important in pathogenesis. The increase in the percentage area of fibrosis from the outer to the inner third of the left ventricular free wall in hypertrophic cardiomyopathy and in hypertension probably reflected transmural gradients of wall stress and myocardial fibre diameter. Although fibrosis is not specific to hypertrophic cardiomyopathy, its quantification and analysis of its regional distribution provide information that is useful in investigating the pathophysiology of the disorder.     

Diabetes,diabetic complications,and blood pressure targets

Association of diabetes with hypertension is frequent and it well known that high blood pressure potentiates the probability of diabetic patients to develop macrovascularand microvascular complications. Strong evidence obtained in a number of large scale prospective studies indicates that adequate blood pressure control in diabetic patients is highly beneficial for prevention of cardiovascular events. Nonetheless, only a limited proportion of hypertensive-diabetic individuals included in studies on anti-hypertensive treatment has met the predefined blood pressure goal. The optimal blood pressure goal to be pursued in diabetic patients with hypertension to guarantee effective protection from cardiovascular outcomes is still under intense debate and recommendations of current guidelines on hypertension treatment are still inconsistent. We comment here on the most important studies and conclude that current evidence does not conclusively support the need to reach a blood pressure target in hypertensive patients with diabetes different from nondiabetic hypertensive individuals.     

Role of diabetes in congestive heart failure: the Framingham study

The incidence of congestive heart failure was determined in relation to prior diabetic status in 5,209 men and women aged 30 to 62 years followed up for 18 years in the Framingham study. Men aged 45 to 74 years had more than twice the frequency of congestive failure as their nondiabetic cohorts, and diabetic women had a fivefold increased risk. This excessive risk appears to be caused by factors other than accelerated atherogenesis and coronary heart disease. Even when patients with prior coronary or rheumatic heart disease were excluded, the diabetic subjects had a four- to fivefold increased risk of congestive heart failure. In women (but not men) with prior coronary disease, diabetes also imposed a threefold increased risk of congestive failure. Furthermore, the increased risk of heart failure in the diabetic patients persisted after taking into account age, blood pressure, weight and cholesterol values as well as coronary heart disease. Women with diabetes appeared to be especially vulnerable and, irrespective of coronary disease status, had twice the frequency of congestive heart failure as men. The excessive risk of heart failure among diabetic subjects was confined to those treated with insulin. The data suggest that diabetes is another discrete cause of congestive heart failure and that some form of cardiomyopathy is associated with diabetes, as a result of either small vessel disease or metabolic disorders.     

Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A

Natriuretic peptides, produced in the heart, bind to the natriuretic peptide receptor A (NPRA) and cause vasodilation and natriuresis important in the regulation of blood pressure. We here report that mice lacking a functional Npr1 gene coding for NPRA have elevated blood pressures and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease. Echocardiographic evaluation of the mice demonstrated a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation are evident but with no reduction in ventricular performance. Nevertheless, sudden death, with morphologic evidence indicative in some animals of congestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 16 females in our study. Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients.     

糖尿病合并非ST段抬高急性冠状动脉综合征患者的临床特点、治疗及远期预后

目的 了解糖尿病合并非ST段抬高急性冠状动脉综合征(ACS)患者的临床特点、治疗及远期预后.方法 在我国北方38个中心连续入选因非ST段抬高ACS住院的患者,记录既往病史、入院情况、住院期间主要治疗和心血管事件,并在发病6、12和24个月对所有患者进行随访.采用Kaplan-Meier牛存分析比较糖尿病和非糖尿病患者2年累计事件发生率,Cox回归多因素分析用于2年累计死亡影响因素的识别.结果 共注册非ST段抬高ACS住院患者2294例,其中已知糖尿病患者420例,占18.3%.平均年龄(64.9±6.7)岁,高于非糖尿病患者的(62.3±8.6)岁(P<0.01),女性患者(占48.1%)、既往有高血压病、心肌梗死、心力衰竭、卒中者均多于非糖尿病患者.合并糖尿病患者住院期间抗血小板约物的应用(92.1%比95.0%,P<0.05)、接受冠状动脉造影(30.0%比36.3%,P<0.05)和冠状动脉介入治疗(12.1%比18.8%,P<0.05)的患者少于非糖尿病者.住院期间以及2年累计的死亡、慢性心力衰竭以及心肌梗死、卒中、心力衰竭和死亡的联合终点事件发生率均明显高于非糖尿病者.多因素回归分析显示,年龄≥70岁、糖尿病、既往心肌梗死、既往心力衰竭、就诊时收缩压<90 mm Hg(1 mm Hg=0.133 kPa)和心率>100次/min是非ST段抬高ACS患者2年死亡的危险因素.结论 合并糖尿病的非ST段抬高ACS患者住院期间和2年死亡、慢性心力衰竭和联合终点事件发牛率明显高于非糖尿病者.糖尿病是非ST段抬高ACS患者2年死亡的独立危险因素.我国非ST段抬高ACS患者住院期间抗血小板治疗和早期介入检杳和治疗有待加强.有必要进行更有针对性的大规模临床研究,以提高糖尿病并发ACS的治疗水平,改善该人群的预后.

Abstract：

Objective To observe the clinical characteristics,treatment options and outcome of diabetic patients with non-ST elevation acute coronary syndromes(NSTEACS).Methods Consecutive patients admitted with NSTEACS from 38 centers in north China were enrolled.Medical histories,clinical characteristics,treatments and outcomes were evaluated and follow-up was made at 6,12,and 24 months 'after their initial hospital admission.Cumulative event rates were compared between diabetic and nondiabetic patients.Results There were 420 diabetic patients out of 2294 NSTEACS patients(18.3%).Diabetic patients were older[(64.9±6.7)years vs.(62.3±8.6)years,P<0.01],more often women (48.1% vs.35.3%,P<0.05)and were associated with higher baseline comorbidities such as previous hypertension,myocardial infarction,congestive heart failure and stroke than non-diabetic patients.The incidence of antiplatelet therapy(92.1% vs.95.O%,P<0.05),coronary angiography(30.0% vs.36.3%,P<0.05)and revascularization(12.1% vs.18.8%,P<0.05)was lower in patients with diabetes than non-diabetic patients.In hospital and 2-year mortality as well as the incidence of congestive heart failure and composite outcomes of myocardial infarction,stroke,congestive heart failure and death were substantially higher in diabetic patients compared with non-diabetic patients.Muhivariative Cox regression analysis revealed that age≥70 years,diabetes,previous myocardial infarction,previous congestive heart failure,systolic blood pressure less than 90 mm Hg(1 mm Hg=0.133 kPa)and heart rate more than 100bpm at admission were risk factors for 2-year death.Conclusion In NSTEACS,diabetes is associated with higher rate of in-hospital and 2-year death,congestive heart failure and composite outcomes of myocardial infarction,stroke,congestive heart failure and death.Diabetes mellitus is a major independent predictor of 2-year mortaliy post NSTEACS.Status of antiplatelet therapy,coronary angiography and revascularization should be improved for diabetic patients with NSTEACS during hospitalization.     

Morphological characteristics in diabetic cardiomyopathy associated with autophagy

Diabetic cardiomyopathy, clinically diagnosed as ventricular dysfunction in the absence of coronary atherosclerosis or hypertension in diabetic patients, is a cardiac muscle-specific disease that increases the risk of heart failure and mortality. Its clinical course is characterized initially by diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure from an uncertain mechanism. Light microscopic features such as interstitial fibrosis, inflammation, and cardiomyocyte hypertrophy are observed in diabetic cardiomyopathy, but are common to failing hearts generally and are not specific to diabetic cardiomyopathy. Electron microscopic studies of biopsy samples from diabetic patients with heart failure have revealed that the essential mechanism underlying diabetic cardiomyopathy involves thickening of the capillary basement membrane, accumulation of lipid droplets, and glycogen as well as increased numbers of autophagic vacuoles within cardiomyocytes. Autophagy is a conserved mechanism that contributes to maintaining intracellular homeostasis by degrading long-lived proteins and damaged organelles and is observed more often in cardiomyocytes within failing hearts. Diabetes mellitus (DM) impairs cardiac metabolism and leads to dysregulation of energy substrates that contribute to cardiac autophagy. However, a “snapshot” showing greater numbers of autophagic vacuoles within cardiomyocytes may indicate that autophagy is activated into phagophore formation or is suppressed due to impairment of the lysosomal degradation step. Recent in vivo studies have shed light on the underlying molecular mechanism governing autophagy and its essential meaning in the diabetic heart. Autophagic responses to diabetic cardiomyopathy differ between diabetic types: they are enhanced in type 1 DM, but are suppressed in type 2 DM. This difference provides important insight into the pathophysiology of diabetic cardiomyopathy. Here, we review recent advances in our understanding of the pathophysiology of diabetic cardiomyopathy, paying particular attention to autophagy in the heart, and discuss the therapeutic potential of interventions modulating autophagy in diabetic cardiomyopathy.     

Echocardiographic features of hypertensive-diabetic heart muscle disease

Computerized M-mode echocardiography was used to evaluate left ventricular anatomy and function in 20 patients with hypertension and diabetes mellitus, without signs of overt heart disease. A similar study was performed in 20 patients with hypertension of similar severity and duration and in 20 normal subjects. Mean posterior wall thickness and mean septal thickness were increased in hypertensive patients compared to normal (p less than 0.001), but diabetic patients had thicker septa with respect to nondiabetics (p less than 0.05). All hypertensive-diabetic patients had reduced peak lengthening rate and/or peak velocity of posterior wall thinning. Six of them also had reduced peak Vcf and/or peak velocity of posterior wall thickening. Only 9 of the 20 patients with hypertension alone had abnormal diastolic function; 4 out of these 9 also had abnormal systolic function. We conclude that diabetes causes more severe impairment of left ventricular function in patients with a similar degree of hypertension. The more consistent abnormalities are reduced rate of dimension increase during filling and slower wall thinning, suggesting impaired left ventricular relaxation and distensibility.     

Myocardial structure in various forms of hypertrophy. II. Myocyte hypertrophy or hyperplasia? Results of the study

In 103 hearts with various forms of cardiac muscle hypertrophy the following parameters were estimated: diameter, length, volume, density and number of myocytes, as well as the density of nuclei of myocytes. The values of all histometric parameters correlated well with the LV weight up to 350 g. In heavier hearts these parameters were approximately at the same magnitude. The number of myocytes was significantly higher in hearts with LV weight above 250 g than in hearts below 250 g: 5.53 x 10(9) vs 4.31 x 10(9), p less than 0.001. The influence of coronary artery diameters, degree of atherosclerosis, weight and percent of fibrous tissue and age on LV weight were evaluated as well. Only coronary artery diameters significantly influenced on LV weight. On the basis of linear discriminant function, three classes of hearts were separated: 1) LV weight 250 g - absence of hyperplasia, only hypertrophy 2) LV weight 251-350 g - hypertrophy + signs of hyperplasia 3) LV weight 350 g - marked signs of hyperplasia Among 18 patients with the LV weight above 350 g (all patients with congestive heart failure), 11 suffered from valvular disease, 3 were postinfarction patients, 2 suffered from primary hypertension and 2 from primary congestive cardiomyopathy. It indicates that, irrespective to the etiologic factor, hyperplasia is a simple result of the cardiac muscle mass increase.     

Diabetic cardiomyopathy

Summary Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years. Pathological studies show left ventricular hypertrophy and fibrosis with varying degrees of small vessel disease, the functional significance of which is uncertain. Hypertension was recognized as an important cofactor in the development of fatal congestive heart failure in diabetics. On cardiac catheterization, in patients symptomatic of heart failure, either congestive or restrictive patterns have been observed. In contrast, asymptomatic diabetics had decreased left ventricular compliance but normal systolic function on hemodynamic study. Noninvasive studies show alterations in systolic and especially diastolic function, particularly in diabetics with microvascular complications and/or coexistent hypertension. Using load-independent measures of contractility, however, systolic function was generally found to be normal in asymptomatic normotensive diabetics. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. Decreased left ventricular compliance and increased interstitial connective tissue were observed in chronically diabetic dogs. In contrast, ventricular myocardium from diabetic rats exhibits a reversible decrease in the speed of contraction, prolongation of contraction, and a delay in relaxation. These mechanical changes are associated with a decreased myosin ATPase, a shift in myosin isoenzyme distribution, alterations in a variety of Ca²⁺ fluxes, and changes in responses to alpha- and beta-adrenergic and cholinergic stimulation. These biochemical changes may be secondary to alterations in carbohydrate, lipid, and adenine nucleotide metabolism in the diabetic heart. When drug induced diabetes was combined with hypertension, a lethal cardiomyopathy with increased left ventricular hypertrophy and fibrosis, increased microvascular pathology and pulmonary congestion were observed. Compared to animals with isolated diabetes or hypertension, greater changes in papillary muscle function, isolated perfused heart performance, cellular electrophysiology, and contractile protein biochemistry were observed. Several studies suggest a protective effect of calcium channel blockers (verapamil and diltiazem) in experimental diabetic cardiomyopathy. Currently the clinical approach to this disorder emphasizes control of hyperglycemia and coexistent hypertension.     

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes

AIMS: Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. METHODS AND RESULTS: Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). CONCLUSION: In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.     

Plasma urotensin II level in patients with chronic congestive heart failure

Urotensin II (UTII) is recently discovered neurohumoral factor influencing function and structure of the myocardium and remodeling of the vessels, and it may contribute to pathogenesis of chronic congestive heart failure. The aim of the study was estimation of plasma concentration of UTII in patients with chronic congestive heart failure. The investigations were performed on 79 patients (37 women and 42 men) aged 43-87 yr. (mean 69.2 +/- 9.8 yr.) and 15 healthy individuals. In all patients, echocardiographic examination of the left ventricle structure and function was performed and serum concentration of electrolytes and creatinine were measured. Plasma levels of UTII were determined before treatment and after 1 week, 2 and 4 weeks of treatment using RIA Peninsula Lab. Inc. Plasma level of UTII in patients suffering from chronic congestive heart failure was significantly lower than in healthy individuals before the treatment and after achieving compensation of the circulatory system using standard treatment, independently from sex, kind of heart failure (systolic-diastolic or diastolic) or coexistence arterial hypertension or pulmonary hypertension, ischemic heart disease or diabetes and impaired glucose tolerance. Treatment of chronic congestive heart failure resulted in a transient increase in UTII concentration except for patients with diastolic heart failure or diabetes. Only patients without ischemic heart disease have a permanent increase in UTII concentration at the time of the treatment. After achieving compensation of the circulatory system in the patients suffering from systolic-diastolic heart failure, UTII concentration was significantly lower than in the patients suffering from diastolic heart failure, in the patients suffering from ischemic heart disease significantly lower than in patients without ischemic heart disease, in the patients with arterial hypertension significantly higher than in those with normal arterial tension, in group of the patients with pulmonary hypertension lower than in group of the patients without pulmonary hypertension and significantly higher in group of the patients suffering from diabetes or impaired glucose tolerance than in group of the patients without this metabolic disorders.     

Left Ventricular Dysfunction in Diabetes

Patients with diabetes mellitus have a greater morbidity and mortality from cardiovascular disease than patients without diabetes. Concomitant hypertension and diabetes are associated with even greater risk of coronary disease, atherosclerotic and peripheral vascular disease, and congestive heart failure. In addition, an independent left ventricular dysfunction (diabetic cardiomyopathy) exists in patients with diabetes that may manifest itself initially as abnormalities in diastolic function but ultimately in systolic function. Firm evidence for this outcome exists experimentally, and reversal of systolic and diastolic abnormalities has been noted experimentally. The Diabetes Control and Complications Trial (DCCT) indicated that intensive glycemic control ameliorates microvascular complication of neuropathy, proteinuria, and retinopathy. Little evidence exists for macrovascular complications or for left ventricular dysfunction. Preliminary results of a canine study of glycemic control and left ventricular function are presented. Clinical correlates of this study and its results are meager. Determination of the role that glycemic control plays with regard to left ventricular systolic function and congestive heart failure awaits carefully controlled and designed clinical trials.     

高血压病史对老年急性心肌梗塞患者近期预后的影响

对270例连续住院急性心肌梗塞(AMI)患者观察了高血压病史对老年 AMI 近期预后的影响。结果表明,老年组中有高血压病史者住院死亡率和心衰明显多于老年组中相同病史患者;老年和非老年组中有单纯高血压病史者肌酸激酶(CPK)峰值与无病史患者无明显差异,而老年组中有高血压病史患者和无病史患者的 CPK 峰值均显著低于非老年组相同病史患者(201±134对263±141;217±129对344±127IU)。提示长时间高血压引起的症状性和无症状性心肌缺血反复发作可促使侧支血管形成,老年人虽 AMI 时 CPK 峰值低,预后却较差。     

A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension

Summary The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n=6), and patient with hypertension (n=3), diabetes mellitus (n=8), and diabetes with hypertension (n=8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.     

SOME FACTORS AFFECTING RIGHT AND LEFT ATRIAL WEIGHTS AND VOLUMES AND TOTAL HEART WEIGHT

The hearts from 156 patients who came to routine hospital autopsy were examined. The amount of epicardial fat was assessed by macroscopic examination, the amount of atrial fat was assessed by microscopic examination and the thickness of the body fat was measured at the midline ventral incision. The patient's age, sex, and height were recorded, and the degree of rigor mortis of the heart assessed. The hearts were weighed, the volume of each atrium was measured, and the atria were individually dissected and weighed. Correlations were sought between atrial weights and volumes and the patient's age, sex, height, amount of body and heart fat, and the degree of rigor mortis of the heart. The total heart weight, both atrial weights and both atrial volumes were greater for males than for females. For each sex the right atrial volume was significantly greater than the left atrial volume, but right and left atrial weights did not differ significantly. Significant positive correlations existed between right and left atrial weights. For both sexes, also, each atrial weight was correlated with its corresponding atrial volume. For males, atrial magnitudes were positively correlated with body height and with the thickness of body fat. For females, left atrial volumes only were positively correlated with the thickness of body fat, and there were no positive correlations with height. For females, but not for males, both atrial weights were positively correlated with age. The total heart weight for males was greatest in taller, fatter subjects, but for females it was greatest in shorter, fatter subjects. For both sexes, atrial magnitudes correlated positively with total heart weight, independently of the amount of heart fat. The amount of epicardial fat (assessed by macroscopic examination) was positively correlated with the thickness of subcutaneous fat, while the amount of atrial fat (assessed by microscopic examination) was not.