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Left ventricular performance and autonomic dysfunction in patients with long-term insulin-dependent diabetes mellitus
Abstract
Cardiac autonomic neuropathy (CAN) is a very frequent complication of insulin-dependent mellitus type 1, affecting the sympathetic or parasympathetic sections or both. The different impairment in the two sections might modify left ventricular function early. To evaluate this relationship, we studied 61 patients (mean age 39.6 +/- 7 years) with type 1 diabetes for more than 10 years, without coronary artery disease (CAD); negative ergometric stress test) and without other pathologies that could interfere with ventricular function. All patients underwent MONO-, 2-dimensional and Doppler echocardiographic examination and radionuclide angiography with 99Tc (RNA). According to the outcome of the Ewing tests, patients were divided into two groups: group A with two or more tests altered (26 patients with CAN) and group B with one or no tests altered (35 patients without CAN). No significant differences between the two groups were found in the systolic function parameters with either technique. In contrast, a pattern of abnormal relaxation was found for the diastolic function parameters: in group A a decrease in E-wave velocity and its time-velocity integral and an increase in A-wave and its time-velocity integral were detected with echocardiography. Moreover, RNA showed a reduced peak filling rate and an increased isovolumic relaxation time. When compared with normal values, an abnormal diastolic filling, defined as two independent echocardiography plus one RNA variable impairment, was found in 15 patients (57.6%) in group A and in only 4 patients (11.4%) in group B (P < 0.001). Our findings suggest an early involvement of diastolic function in patients with CAN.
... Several authors have evaluated the type 1 diabetic population in order to assess the existence of early echocardiographic alterations of asymptomatic ventricular dysfunction related to CAP. Irace, et al. [20] in their 1996 publication, already showed that type 1 diabetic patients with CAP had alterations in Left Ventricular (LV) diastolic function expressed as lower E wave velocity and higher transmittal flow A wave velocity, without evidence of alterations in systolic function. Similarly Wille Heimer, et al. [21] found that out of a total of 34 type 1 diabetic patients CAP was present in 21 patients when evaluated with PRAC and the presence of impaired LV diastolic function expressed as a lower E/A ratio was significantly higher in this group with CAP. ...
... One of the pathophysiological aspects related to cardiac autonomic neuropathy is the development of ventricular dysfunction. This association has been demonstrated mainly for the LV [20][21][22][23] and so far nothing has been published in the right ventricle. Therefore, the most important contribution of our research lies in the fact that we demonstrated that 61.5% of diabetic patients with impaired right ventricular diastolic function showed an altered Valsalva index ratio compared to the group without right ventricular dysfunction, 91.7% of whom did not present this alteration, which allowed us to demonstrate that dysfunction of the cardiac autonomic nervous system manifested mainly by an abnormal Valsalva index ratio is associated with DDVD. ...
... In these patients, AF is related to an increased left ventricular mass evaluated by echocardiography [14] and cardiac magnetic resonance [15], independently of age, sex, 24-h ABPM values, and other clinical characteristics. Moreover, in these patients, diastolic function is also impaired [16]. These changes are related to increased sympathetic tone, increased BP variability, 123 decreased heart rate variability, and impaired myocardial blood flow regulation [17][18][19]. ...
Patients with autonomic failure are characterized by orthostatic hypotension, supine hypertension, high blood pressure variability, blunted heart rate variability, and often have a "non-dipping" or "reverse dipping" pattern on 24-h ambulatory blood pressure monitoring. These alterations may lead to cardiovascular and cerebrovascular changes, similar to the target organ damage found in hypertension. Often patients with autonomic failure are on treatment with anti-hypotensive drugs, which may worsen supine hypertension. The aim of this review is to summarize the evidence for cardiac, vascular, renal, and cerebrovascular damage in patients with autonomic failure.
... Neben der Manifestation einer koronaren Herzkrankheit [1] konnte durch verschiedene klinische Untersuchungen aufgezeigt werden, daß die Herzinsuffizienz mit frühzeitiger diastolischer Dysfunktion aufgrund sekundärer Herzmuskelveränderungen eine bedeutende prognoselimitierende Rolle spielt [2][3][4][5][6]. Als mögliche Einflußgrößen für die Entstehung einer diabetischen Herzerkrankung [7,8] werden neben koronarmorphologischen Veränderungen im Sinne einer progredient verlaufenden Arteriosklerose mikroangiopathische Prozesse, eine direkte myokardiale Beteiligung durch Fibrosierung und eine autonome Neuropathie mit Beeinflussung der kardialen Innervation mit einem erhöhten Risiko für den plötzlichen Herztod diskutiert. Verschiedene Autoren konnten Ende der 80er Jahre zeigen, daß bei Typ-I-Diabetikern mit einer in Ruhe normalen linksventriku-lären Auswurffraktion bereits ein eingeschränkter Anstieg der linksventrikulären Ejektionsfraktion während Belastung gegenüber nichtdiabetischen Kontrollen nachweisbar ist [9,10]. ...
Kurzfassung: Hintergrund: Da die Prognose der Pati-enten mit Diabetes mellitus durch die kardialen Mani-festationen bestimmt wird, kommt einer frühzeitigen Erkennung eines beginnenden kardialen Endorganscha-dens eine besondere Bedeutung zu. In dieser Studie sollte untersucht werden, ob mittels Dobutamin-Streßecho-kardiographie frühzeitig eine diabetische Kardiomyopa-thie erfaßt werden kann. Patienten und Methodik: Bei 47 kardial unauffälli-gen Typ-I-Diabetikern (25 ± 3 Jahre) und 33 altersent-sprechenden Kontrollpersonen wurde eine echokardio-graphische Untersuchung in Ruhe und unter pharmako-logischer Belastung mit Dobutamin durchgeführt. Bei allen Personen erfolgte in Ruhe und unmittelbar nach Belastung die Bestimmung morphologischer Parame-ter und diastolischer Füllungsparameter inklusive Be-stimmung der Pulmonalvenenflüsse. Ergebnisse: In Ruhe zeigte sich bei allen Typ-I-Dia-betikern eine diastolische Dysfunktion im Sinne einer Relaxationsstörung. Dobutamin wurde bis zu einer Maxi-maldosis von 40 µg/kg KG/min infundiert. Bei Aus-belastung zeigten sich bei 7 Typ-I-Diabetikern regiona-le systolische Wandbewegungsstörungen. Bei diesen 7 und weiteren 9 Typ-I-Diabetikern (n = 16) zeigte sich unmittelbar nach Ausbelastung eine diastolische Dys-funktion im Sinne eines restriktiven diastolischen Fül-lungsmusters. Bei 14 Patienten erfolgte der Nachweis einer sogenannten "Pseudonormalisierung", und 17 Patienten hatten eine diastolische Dysfunktion im Sinne einer gestörten Relaxation. Bei den 16 Diabetikern mit restriktivem Füllungsmuster wurden vermehrt Herzrhyth-musstörungen in der Nachbelastungsphase dokumen-tiert. Schlußfolgerung: Bei einigen Typ-I-Diabetikern deck-te die adrenerge kardiale Belastung ein restriktives diastolisches Füllungsmuster und eine vermehrte atriale Arrhythmieneigung in der Nachbelastungsphase auf.
Aim: Cardiac autonomic neuropathy (CAN) is a common and important chronic complication in diabetic patients. Heart failure resulting from cardiomyopathy is also a lethal complication in diabetic patients. However, data showing the exact association between CAN and heart failure in diabetic patients are relatively scarce. Therefore, our study aimed to determine the association between the parameters assessing CAN and heart function in diabetic patients.
Method: The medical records of type 2 diabetic patients who underwent an autonomic function test with heart rate variability (HRV) and echocardiography were reviewed from January 2018 to December 2018. A total of 100 type 2 diabetic patients were included, and the association between the parameters assessing CAN and heart function was analysed.
Results: Among the 100 analysed patients, 65 were diagnosed with CAN and 26 showed diastolic dysfunction. Moreover, 19 (73.1%) diabetic patients with diastolic dysfunction were complicated with CAN. The occurrence of diastolic dysfunction was higher in diabetic patients with CAN than in diabetic patients without CAN (29.2% vs 20.0%, p < 0.05), and the occurrence of CAN was higher in diabetic patients with diastolic dysfunction than in patients without diastolic dysfunction (73.1% vs 62.2%, p < 0.05). However, there were no significant associations between HRV parameters and heart function.
Conclusion: We demonstrated that diastolic dysfunction is more common in diabetic patients complicated with CAN than in diabetic patients without CAN, although several diabetic patients without diastolic dysfunction are also diagnosed with CAN. Moreover, further studies about the long-term serial monitoring of heart function according to the progression of CAN are required to confirm the exact association between CAN and heart function.
The aim was to investigate ventricular myocardial functions in patients with type II diabetes mellitus (DM) with cardiovascular autonomic neuropathy (CAN) in correlation with serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP). We studied 56 patients with type II DM of >5 years’ duration. Thirty healthy subjects matched for age and sex served as control group. The patients with type II DM were divided into two groups according to the outcome of the autonomic nerve function tests as those with CAN (DM + CAN) and without CAN (DM). Echocardiographic studies were performed to assess ventricular functions. NT-pro-BNP levels were measured in all patients. Subclinical left ventricular diastolic dysfunction was not different between diabetic patients with CAN (84 %) and those without CAN (74.2 %); all of them were classified as impaired relaxation pattern (p > 0.05). Subclinical right ventricular diastolic dysfunction was not also different between diabetic patients with CAN (48 %) and those without CAN (32.3 %) (p > 0.05). The NT-pro-BNP levels were not different between patient groups and not significantly increased in patients with diastolic dysfunction. Multivariate logistic regression analysis demonstrated that only diabetes mellitus was associated with diastolic dysfunction (OR 5.8, 95 % CI 1.7–19.2, p = 0.004). NT-pro-BNP is not significantly elevated in diabetic patients with subclinical mild diastolic dysfunction which is not related to CAN.
Background: Since the prognosis of patients with insulin dependent diabetes mellitus is generally limited by secondary cardiac complications, an early determination of the myocardial manifestation is of considerable importance. The aim of this study was to investigate whether dobutamine stress echocardiography is a suitable method for the detection of early signs of diabetic cardiomyopathy. Patients and Methods: Using echocardiography (at rest and during dobutamine infusion), we examined 47 young patients with insulin dependent diabetes mellitus (25 ± 3 years) and 33 age- and sex-matched subjects without cardiac disease and without diabetes mellitus. Using M-mode echocardiography morphological parameters and systolic function were determined. The parameters of LV diastolic function were assessed by Doppler echocardiographic analysis. Results: All type-I diabetics showed a normal systolic function and a "delayed relaxation pattern" at rest. Under maximal dobutamine stress echocardiography in seven patients a regional systolic wall motion disorder was detected. These seven patients and nine further diabetics had a diastolic dysfunction in terms of a restrictive diastolic filling pattern at stress. In 14 patients with diabetes mellitus pseudonormalisation was documented and 17 patients showed an unchanged "delayed relaxation pattern" at stress. Atrial and ventricular arrhythmias more often occurred in the 16 patients with the restrictive filling pattern (p< 0.01). Conclusion: In patients with insulin dependent diabetes mellitus adrenergic cardiac stress reveals left ventricular diastolic dysfunction because of an increase of the heart rate and blood pressure. Patients with restrictive diastolic dysfunction particularly suffer from frequently occurring atrial arrhythmias.
We analyzed left ventricular (LV) diastolic dysfunction prevalence and features in 142 subjects with type 2 diabetes without valvular disease, atrial fibrillation, or ischemic heart disease history. The E/A ratio before and during the Valsalva maneuver was assessed with pulsed doppler and the E/Ea ratio (early transmitral to early diastolic annular velocity ratio) with pulsed tissue doppler imaging. The ejection fraction exceeded 50% in all subjects. LV diastolic function was normal in 75 (52.8%) and LV diastolic dysfunction found in 67 (47.2%), of whom 16 (11.3%) showed a pseudonormal pattern. Those with LV diastolic dysfunction were older than those with normal function. Multiple logistic regression analysis showed that age ≧65 years [(Odds ratio: 5.67 (95% CI, 2.48-12.96), p<0.0001], resting heart rate ≧70 bpm [(2.18 (1.024.65), p<0.0441)], and shortduration diabetes [(0.49 (0.27-0.88), p< 0.0163)] were at risk for LV diastolic dysfunction. Those with diastolic dysfunction were older even in their diabetes-duration subgroup than those without of less than 10 years. These findings suggest that diastolic dysfunction in type 2 diabetes is prevalent in those older and considerably influenced by aging.
The prevalence of diabetes in Spain is about 6% and increases with age and obesity. Diabetes is present in approximately 25% of patients with coronary heart disease (CHD). Pre-diabetic and diabetic patients have a higher incidence of CHD and poorer prognosis, with high short-and long-term mortality. The protective effect of pre-menopause status is suppressed by diabetes. Diabetes has a synergic effect with other cardiovascular risk factors. Primary prevention in diabetic patients should be approached as in non-diabetic post-infarction patients. In diabetes, a healthy life-style and strict control of blood sugar and the other cardiovascular risk factors, particularly hypertension, is mandatory.
Left ventricular (LV) preload changes may alter exercise tolerance (ET), probably lessening activation of the Maestrini-Starling mechanism. Reduced LV filling (pre-load) during the diastolic phase, usually impaired in diabetic patients, could affect ventricular function.
To evaluate the relationship between some echocardiographic LV function indices and ET, 24 patients (age 43-75 years, mean 54 +/- 13 years, Group A) with type II diabetes mellitus (DM), not suffering from other pathologies, and for whom the ergometric stress test (EST) resulted in an early interruption because of muscular fatigue and/or dyspnea, and 14 patients (age 38-70 years, mean 53 +/- 12 years, Group B) with type II DM and maximal ergometric stress test, used as control group, were studied.
The EST was performed by increasing the load by 25 W every 2 min; its duration was used as an ET index and correlated with clinical parameters of LV function obtained with M-mode, two-dimensional, and Doppler echocardiography.
No patients in either Group A or Group B showed a high systolic blood pressure value at rest and/or an LV hypertrophy and/or an alteration of systolic functional indices. In neither group was there significant correlation between ET and duration of DM, basal heart rate, basal and max systolic blood pressure, and EF values. Linear regression analysis showed a significant correlation between Doppler parameters of the diastolic function and ET index in Group A, while there was no significant correlation in Group B.
From these data we can deduce that in absence of left systolic ventricular dysfunction the impairment of LV relaxation in DM can influence exercise tolerance, probably by limiting activation of the contractile reserve.
This chapter describes the effects of autonomic denervation in diabetic patients. Autonomic neuropathy as defined by abnormal autonomic tests is common but symptoms are rare. However when present, they can be devastating. Cardiovascular autonomic neuropathy leads to an approximately five fold risk of mortality. Autonomic neuropathy can result in hemodynamic and structural changes in the arterial system. This chapter discusses the epidemiology, etiology, and pathology of autonomic neuropathy. It then describes the effect of autonomic neuropathy on the cardiovascular, gastrointestinal, genitourinary, and respiratory systems. It outlines the effects of autonomic denervation on sweating, pupillary reflexes, the response to hypoglycemia, and erythropoietin production. Finally it discusses the clinical associations of autonomic neuropathy and concludes with a summary of its natural history, mortality, and management. Autonomic neuropathy is an important complication of diabetes, resulting in increased patient morbidity and mortality.
Introduction: The early determination of the myocardial manifestation is of considerable importance, since the prognosis of patients (P) with insulin dependent diabetes mellitus (IDDM) is generally masked by secondary cardiac complications. The aim of this study was to investigate whether young, asymptomatic P with IDDM and persisting normal systolic left ventricular (LV) function already show a diastolic LV dysfunction.
Methods: An echocardiographical examination of 92 IDDM patients (age: 25 ± 4 years) without known cardiac disease and of 50 control persons (C) of similar ages was carried out. P with a cardiac disease or long-term diabetic syndrome were excluded. Using M-mode echocardiography, morphological parameters and systolic time-intervals (fractional shortening; ejection fraction) were determined. Doppler indices were then measured: maximal early and late diastolic flow velocity (VE; VA), E/A ratio, acceleration and deceleration time (DT), isovolumetric relaxation time (IVRT).
Results: Although the left atrial and left ventricular dimensions, as well as the systolic functional parameters of all P with IDDM were normal, they showed a diastolic dysfunction with a reduction of the early diastolic filling (VE; 0.54 ± 0.07 m/s vs 0.72 ± 0.04 m/s; p < 0.01) and the E/A ratio (0.9 ± 0.15 vs 1.99 ± 0.22; p < 0.01), an increase in the atrial filling (VA; 0.76 ± 0.05 m/s vs 0.39 ± 0.04 m/s, p < 0.01), an extension of the IVRT (129 ± 23 ms vs 78 ± 6 ms, p < 0.01), and an increased DT (248 ± 27 ms vs 188 ± 8 ms, p < 0.01).
Conclusion: Even young P with IDDM, with a normal systolic ventricular function, suffer a diastolic dysfunction which serves as a marker of a diabetic cardiomyopathy. Therefore, echocardiography with measurements of systolic and diastolic functional parameters appears to be a sensible method for evaluating the course of diabetic cardiomyopathy.
Smoking cigarettes induces rapidly occurring and reversible functional changes in the cardiovascular system, which precede morphologic changes. These functional changes are also related to atherosclerotic disease development and thus may qualify as prognostic parameters in chronic smokers. As opposed to smoking-induced morphologic changes functional alterations occur and revert within minutes, thus, allowing for the detection of smoking-induced effects on the cardiovascular system within minutes following exposure to mainstream smoke. Some alterations represent 'direct' changes (e.g., endothelial function), others reflect changes in a different organ system (e.g., the autonomous nervous system influencing heart rate variability), while some represent the sum of alterations in many organs and systems (e.g., exercise performance influenced by the autonomous nervous and by endothelial and cardiac function). Since a specific functional parameter usually changes with at least one or several others, caution should be exercised when trying to establish a direct cause relationship between the alteration of a single parameter and a clinical outcome.
Diabetic cardiomyopathy is a well-defined complication of diabetes that occurs in the absence of ischemic, vascular, and hypertensive disease.
The study was undertaken to test the relationship among autonomic neuropathy (AN), 24-h blood pressure (BP) profile, and left ventricular function.
Nineteen type-1 diabetic patients underwent autonomic tests and echocardiographic examination. Patients were divided according to the presence (AN+) or absence (AN-) of AN.
In the AN+ group (n = 8), the E/A ratio at echo was lower than in the AN- group (n = 11) (1.1 +/- 0.3 vs. 1.6 +/- 0.3; p < 0.005). Systolic and diastolic BP reductions during sleep were smaller in the AN+ than in the AN- group (6.6 +/- 6.6 vs. 13.0 +/- 4.3%; p < 0.03 for systolic and 12.8 +/- 6.8 vs. 20.0 +/- 4.0% for diastolic BP reduction; p < 0.03, respectively). Considering all patients, the E/A ratio correlated inversely with awake diastolic BP (r - 0.63; p = 0.005); sleep systolic BP (r - 0.48; p = 0.04), and sleep diastolic BP (r - 0.67; p = 0.002). The AN correlated with diastolic interventricular septum thickness (r 0.57; p = 0.01), sleep systolic BP (r 0.45; p = 0.05), sleep diastolic BP (r 0.54; p = 0.02), and correlated inversely with systolic and diastolic sleep BP reduction (r - 0.49; p = 0.03 and r - 0.67; p = 0.002, respectively). Finally, E/A ratio and AN score correlated between themselves (r - 0.6; p = 0.005).
Our results suggest that left ventricular diastolic dysfunction may be detected very early in type-1 diabetic patients with AN. Parasympathetic lesion and nocturnal elevations in BP could be the link between AN and diastolic ventricular dysfunction.
Abnormal availability of neurotrophins, such as nerve growth factor (NGF), has been implicated in diabetic somatosensory polyneuropathy. However, the involvement of neurotrophins in diabetic neuropathy of autonomic nerves, particularly the vagus nerve which plays a critical role in visceral afferent and in autonomic motor functions, is unknown. To assess the effects of hyperglycemia on the neurotrophin content and transport in this system, cervical vagus nerves of streptozotocin (STZ)-induced diabetic rats were studied at 8, 16, and 24 weeks after the induction of diabetes. Elevations in vagus nerve hexose (glucose and fructose) and polyol levels (sorbitol), and their normalization with insulin treatment, verified that the STZ treatment resulted in hyperglycemia-induced metabolic abnormalities in the nerve. Neurotrophin (NGF and neurotrophin-3; NT-3) content and axonal transport were assessed in the cervical vagus nerves from nondiabetic control rats, STZ-induced diabetic rats, and diabetic rats treated with insulin. The NGF, but not the NT-3, content of intact vagus nerves from diabetic rats was increased at 8 and 16 weeks (but not at 24 weeks). Using a double-ligation model to assess the transport of endogenous neurotrophins, the retrograde transport of both NGF and NT-3 was found to be significantly reduced in the cervical vagus nerve at later stages of diabetes (16 and 24 weeks). Anterograde transport of NGF or NT-3 was not apparent in the vagus nerve of diabetic or control rats. These data suggest that an increase in vagus nerve NGF is an early, but transient, response to the diabetic hyperglycemia and that a subsequent reduction in neuronal access to NGF and NT-3 secondary to decreased retrograde axonal transport may play a role in diabetes-induced damage to the vagus nerve.
The prevalence of diabetes in Spain is about 6% and increases with age and obesity. Diabetes is present in approximately 25% of patients with coronary heart disease (CHD). Pre-diabetic and diabetic patients have a higher incidence of CHD and poorer prognosis, with high short- and long-term mortality. The protective effect of pre-menopause status is suppressed by diabetes. Diabetes has a synergic effect with other cardiovascular risk factors. Primary prevention in diabetic patients should be approached as in non-diabetic post-infarction patients. In diabetes, a healthy life-style and strict control of blood sugar and the other cardiovascular risk factors, particularly hypertension, is mandatory.
Early determination of myocardial manifestations of diabetes mellitus is of major importance, since myocardial involvement considerably influences the prognosis of diabetic patients. The aim of this study was to investigate whether young patients with insulin-dependent diabetes mellitus and normal systolic left ventricular (LV) function already show a diastolic LV dysfunction and an increased risk of arrhythmias.
Echocardiography was performed in 87 patients suffering from type I diabetes mellitus, without known cardiac disease and in 87 controls. Patients with a known manifest cardiac disease or a long-term diabetic syndrome were excluded. Morphological parameters were determined using M-mode echocardiography. Doppler echocardiography was used to evaluate parameters of LV diastolic function. The risk of arrhythmia was assessed by means of electrocardiography, heart rate variability, and late potential analysis.
The left atrial and ventricular dimensions and systolic functional parameters of all patients were normal. A diastolic dysfunction with a reduction in early diastolic filling, an increase in atrial filling, an extension of isovolumetric relaxation and deceleration time was documented in diabetic patients, as well as an increased number of supraventricular and ventricular premature beats.
Even young patients with diabetes mellitus suffer from a diastolic dysfunction while systolic ventricular function is normal. Therefore, echocardiography with measurements of diastolic functional parameters appears to be a sensitive method for evaluating the manifestation and course of early diabetic cardiomyopathy.
The existence of a diabetic cardiomyopathy has been proposed as evidence has accumulated for the presence of myocardial dysfunction in diabetic patients in the absence of ischemic, valvular or hypertensive heart disease. Diastolic dysfunction has been described as an early sign of this diabetic heart muscle disease preceding the systolic damage. Abnormalities in diastolic performance have been first demonstrated by cardiac catheterisation and subsequently by mainly using echocardiography. The pathogenesis of this left ventricular dysfunction is not clearly understood. Microangiopathy, increased extracellular collagen deposition, or abnormalities in calcium transport alone or in combination are considered to be associated with this dysfunction. The relationship between diastolic dysfunction and glycemic control is still a matter of debate. Some epidemiological and clinical arguments suggest that diastolic abnormalities may contribute to the high morbidity and mortality among diabetic patients. However, the prognostic importance of subclinical diastolic dysfunction and the possibilities for intervention are not fully known. Eventually, despite numerous studies, evidence of an intrinsic diastolic dysfunction in diabetes mellitus remains questionable. Indeed, quite contradictory results have been reported. They have been obtained in small, inhomogeneous populations, with sometimes confounding factors, using various echocardiographic indices with known limitations. Also, further studies using more refined techniques for the evaluation of diastolic function are needed, as a prerequisite, to unequivocally relate diabetes mellitus to a specific cardiomyopathy.
The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy (AN) are largely unknown. The aim was to determine the relative role of AN in the pathogenesis of cardiac diastolic dysfunction and left ventricular hypertrophy in Type 1 diabetes.
Ten Type 1 diabetic patients with AN, defined by cardiovascular tests (AN+) and 10 age- and sex-matched patients without neuropathy (AN-) as well as 10 healthy subjects (C) participated in the study. Left ventricular diastolic function was assessed by Doppler echocardiography, whilst systolic function was evaluated by cine magnetic resonance (MR) imaging.
Doppler echocardiography showed a significant decrease in E/A ratio, i.e. the ratio between peak Early transmitral filling velocity during early diastole (E-wave) and peak transmitral Atrial filling velocity during late diastole (A-wave), in AN+ compared with C (P < 0.01) [0.95 +/- 0.08 (mean +/- sem) (AN+); 1.19 +/- 0.09 (AN-); 1.33 +/- 0.10 (C)]. The E-wave deceleration time was significantly shorter in AN+ compared with AN- and C (P < 0.02) [178 +/- 7 ms (AN+); 203 +/- 9 ms (AN-); 205 +/- 9 ms (C)]. Cine MR imaging showed a significantly greater left ventricular mass index in AN+ compared with C [103 +/- 4 g/m(2) (AN+) vs. 98 +/- 7 (AN-) and 92 +/- 4 g/m(2) (C), P < 0.05].
Autonomic neuropathy is associated with left ventricular hypertrophy and diastolic dysfunction in Type 1 diabetic patients.
This study was designed to determine the effects of type 1 diabetes mellitus (T1DM) on left ventricular (LV) and particularly left atrial (LA) structure and function. We evaluated 88 non-obese subjects: 44 with T1DM, 44 age- and gender-matched normal controls (age 39 +/- 11 years). LV and LA structure and function were quantified using two-dimensional echocardiography, pulse-wave Doppler, and tissue Doppler imaging, including early and late diastolic myocardial velocities (Em global and Am global, respectively). The T1DM subjects averaged higher heart rate, relative wall thickness, and ejection fraction, and lower indexed end-systolic volume than normal controls (P < .001, P < .05, P = .01, and P < .05, respectively). T1DM was related to A wave velocity, Am global, A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .05, P < .0005, P < .001, and P < .0005, respectively). In multivariate analyses, T1DM was an independent predictor of the A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .01, and P < .005, respectively). Thus, despite increased relative wall thickness, LV systolic function is increased and early diastolic filling is normal in T1DM subjects; however, they possess changes in LA transport function suggesting increased reliance on LA contribution to LV filling.
EARLYDETECTIONofimpaired relaxation hasbeen emphasized recently fortheevaluation ofglobal and regional ventricular function inpatients withheart dis- ease.Although early relaxation abnormalities have beenfoundinvarious cardiac diseases, theunderlying mechanisms arenotasyetfully understood. Giventhe recent progressinour understanding ofrelaxation of theheart,' thesemechanisms can now bediscerned more easily. We willfirst summarize our present knowledge ofrelaxation ofcardiac muscle or,more specifically, howrelaxation iscontrolled bythethree following interacting determinants: (1)load, (2)(in)- activation, and(3)nonuniform distribution ofloadand (in)activation inspaceandintime. Then,theconcept oftriple control willbeextended tothatoftheintact heartinsituas a pump. We willalsoreviewhow multiple factors, acting either alone or inconcertde- pending on thenatureofthedisease, underlie early relaxation abnormalities inpatients withheart disease. Finally, measurements ofventricular relaxation will be critically discussed inviewofthese newer concepts. Mechanical aspects ofrelaxation ofisolated cardiac muscle Performance oftheheartduring thecontraction phase, both asamuscle andasamuscle-pump system, isregulated through twodistinct butinterrelated func- tions, namelyheterometric autoregulation or control bychanges inload(volume and/or pressure) andho- meometric autoregulation or control bychanges in contractility. Although regulation ofperformance by changes inloadisconceptually related toheterometric autoregulation andregulation ofperformance by changes incontractility tohomeometric autoregula- tion, theseconcepts are notquiteidentical. Bythe same token, although changes incontractility areusu-
Systolic and diastolic time intervals were used to examine left ventricular performance in 22 young diabetic men (mean age 25 years) with no apparent clinical heart disease. Pre-ejection period index (PEPI), left ventricular ejection time index (LVETI), electromechanical systole index (QS2I), PEP to LVET ratio, the a wave percentage amplitude of the apexcardiogram (a/H5 ratio), the rapid filling wave (RFW), and the A2O interval were obtained in the conventional manner in 22 diabetics and 22 healthy men. The heart rate, diastolic pressure, PEP/LVET ratio, a/H per cent ratio, and A2O interval were significantly increased and LVET decreased in the diabetic group. QS2I, PEPI, and RFW did not differ from that in the normal group. Twenty-three per cent of patients had an abnormal systolic time interval, 54 percent an abnormal diastolic time interval, and 23 per cent had both abnormal intervals. Though these studies provide no difinite evidence of a cause, the abnormalities found may reflect a subclinical diabetic cardiopathy.
ABSTRACT To assess left ventricular (LV) function in diabetes mellitus, M-mode echocardiograms were recorded in 36 insulin-treated diabetic women, mean age 25±6 (SD) years, and 13 healthy women of the same age. Echocardiographic tracings of the septum and LV posterior wall were digitized and continuous plots were made of LV dimension and its rate of change. The pattern of LV filling was abnormal in 19 diabetics, when the mean value ±2 SD in the healthy women was taken as the normal range of the indices. The most common abnormality was a prolonged rapid filling period. The LV systolic function was normal in all diabetics. Diabetics with severe microvascular complications had thicker LV walls (p<0.05) and smaller LV end-diastolic diameters and stroke volumes (p<0.01) than the healthy women. The electrocardiographic voltage was lower in the diabetic group (p<0.05). These studies suggest that minor abnormalities in LV function reflecting stiffness of the myocardium are common in young female diabetics, a patient group with a relatively low prevalence of coronary artery disease.
Six juvenile diabetics [age, 31 ± 2 yr (mean and SEM); duration of diabetes, 15 ± 4 yr] with signs of autonomic neuropathy (decreased beat-to-beat variation in heart rate during deep breathing) and seven control patients of similar age (27 ± 1 yr) and duration of diabetes (14 ± 2 yr) performed graded exercise oh an ergometer cycle. Resting heart rate was higher and the increase in heart rate at the lowest work load (50 W) was diminished in patients with autonomic neuropathy compared with control patients (P < 0.001), indicating a vagal defect.
The relationships in autonomic neuropathy between heart rate and systolic blood pressure, respectively, and relative work load (expressed as oxygen uptake — in percent—of individual maximal oxygen uptake) were identical with previous findings in normal subjects during beta-adrenergic receptor blockade, indicating impaired sympathetic activity. Maximal heart rate was 157 ± 9 min−1 in autonomic neuropathy and 181 ± 4 in controls, P < 0.05; maximal systolic blood pressure was 179 ± 11 mm Hg and 197 ± 5, respectively.
The greatest tolerable work load was significantly less in patients with autonomic neuropathy (125 ± 13 vs. 161 ± 9 w, P < 0.05). Similarly, maximal oxygen uptake was reduced (1.68 ± 0.21 vs. 2.78 ± 0.18 L/min, 25 ± 3 vs. 38 ± 2 ml/min/kg, P < 0.005).
In conclusion, diabetics with decreased beat-to-beat variation in heart rate displayed signs of cardiovascular dysfunction of parasympathetic as well as sympathetic origin during graded exercise.
Four hundred M-mode echocardiographic surveys were distributed to determine interobserver variability in M-mode echocardiographic measurements. This was done with a view toward examining the need and determining the criteria for standardization of measurement. Each survey consisted of five M-mode echocardiograms with a calibration marker, measured by the survey participants anonymously. The echoes were judged of adequate quality for measurement of structures. Seventy-six of the 400 (19%) were returned, allowing comparison of interobserver variability as well as examination of the measurement criteria which were used. Mean measurements and percent uncertainty were derived for each structure for each criterion of measurement. For example, for the aorta, 33% of examiners measured the aorta as an outer/inner or leading edge dimension, and 20% measured it as an outer/outer dimension. The percent uncertainty for the measurement (1.97 SD divided by the mean) showed a mean of 13.8% for the 25 packets of five echoes measured using the former criteria and 24.2% using the latter criteria. For ventricular chamber and cavity measurements, almost one-half of the examiners used the peak of the QRS and one-half of the examiners used the onset of the QRS for determining end-diastole. Estimates of the percent of measurement uncertainty for the septum, posterior wall and left ventricular cavity dimension in this study were 10--25%. They were much higher (40--70%) for the right ventricular cavity and right ventricular anterior wall. The survey shows significant interobserver and interlaboratory variation in measurement when examining the same echoes and indicates a need for ongoing education, quality control and standardization of measurement criteria. Recommendations for new criteria for measurement of M-mode echocardiograms are offered.
Peripheral and autonomic nerve function was assessed in 10 newly diagnosed male diabetics (six insulin-treated and four sulfonylureatreated) with repeated observations over the subsequent six months. There was significant impairment of motor-conduction velocity in the common peroneal nerve at diagnosis in both treatment groups, with improvement following treatment in only the insulin-treated patients.
In contrast, although the blood glucose level fell in both groups, the mean level was significantly lower in the sulfonyhireatreated patients at two months and at each subsequent visit.
In the autonomic function tests significant abnormality was found in the electrocardiographic R-R-interval (beat-to-beat) variation in resting heart rate in two of the insulin-treated patients and all of the sulfonylurea-treated group, with improvement in only one of the latter. One patient in the sulfonylurea-treated group also showed an abnormal response to the Valsalva maneuver (expressed as the Valsalva ratio), and this remained abnormal throughout the period of study. All other patients had normal responses to the Valsalva maneuver and sustained handgrip test. None of the patients had postural hypotension. Abnormalities in autonomic nerve function in diabetics at diagnosis have not been previously reported.
Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.
Sixty patients with type I diabetes mellitus underwent an ergometric stress test (EST) to evaluate the relationship between cardiac autonomic neuropathy (CAN) and hemodynamic changes during EST. All patients were divided into 2 groups: in the Group A were included 26 patients (mean age 43 +/- 9 years) with impairment of 2 or more autonomic tests according to Ewing (patients with CAN) and in the Group B were included 34 patients (mean age 38 +/- 13 years) without CAN. The EST was symptom-limited and performed with load increases of 25 W every 3 min. No positive EST were observed in both groups. Heart rate (HR) at rest and systolic blood pressure (SBP) at maximum common workload were significantly higher in Group A than in Group B. Moreover, a significant linear correlation was found between a CAN score and SBP x HR product at rest and at maximal workload. These findings are correlated with increased sympathetic activity due to a parasympathetic impairment. The data show the relationship between hemodynamic changes during EST and the Ewing test used in the diagnosis of CAN.
Cardiac mortality is more frequent in diabetic patients than in normal subjects and particularly heart failure occurs 4-6 times more frequently in these patients than in normals also excluding diabetics with coronary artery disease (CAD). To study cardiac function, 20 patients with type II diabetes mellitus (11 M and 9 F, mean age 48 +/- 9 years), and 13 normal subjects (6 M and 7 F, mean age 48 +/- 13 years), were submitted to radionuclide ventriculography with technetium 99m to evaluate some indices of cardiac function at rest and during effort. The diabetic patients were on good metabolic control testified by a satisfactory fasting and post prandial glycaemia, absence of glycosuria in the last 3 monthly controls and a normal value of glycosylate haemoglobin; they had no vascular or neurological complications; CAD was excluded submitting these patients to a maximal effort ECG on an ergometer. The normal subjects were comparable to diabetic patients for age, sex, mean arterial pressure, body mass index and body surface area. At rest, stroke volume, peak filling rate, cardiac output, ejection fraction (EF), were significantly lower in diabetic patients than in normal subjects. Systemic vascular resistances (SVR) were higher in diabetics than in normal subjects (p less than 0.01). Mean EF during effort increased in both normals and diabetics but 30% of diabetic patients showed no increase in EF during effort (less than 5%). Preload, represented by end-diastolic volume or blood volume, did not differ in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Doppler echocardiograms of the mitral valve were recorded along with electrocardiograms and respirations from 20 diabetics and 16 normal subjects, all aged 10 to 15 years. E and A areas (the components of the total velocity-time integral in the early passive period of ventricular filling [E] and the late active period of atrial emptying [A], respectively), the peak E and A velocities (cm/s) and the 1/3 area fraction (or the proportion of filling in the first 1/3 of diastole) were measured. Each of the following was significantly greater for the normal subjects versus diabetic patients: peak E (96 +/- 14 vs 81 +/- 14 cm/s, p less than 0.005), E/total area (0.74 +/- 0.04 vs 0.69 +/- 0.06, p less than 0.005) and peak E/A velocity ratio (2.38 +/- 0.55 vs 1.92 +/- 0.55, p less than 0.05). The mean heart rates and ages were not significantly different for the 2 groups. The remaining parameters (peak A velocity, A/total area, E/A area, and 1/3 area fraction) were also not significantly different for the 2 groups. This study is the first to demonstrate diastolic dysfunction in pediatric patients with diabetes and may indicate abnormalities of ventricular relaxation or compliance in diabetes mellitus.
In 16 insulin-dependent diabetic patients, 36 +/- 8 years old with no microangiopathy, hypertension or coronary artery disease, and 16 healthy control subjects matched for sex, age and body surface area, the following parameters were obtained by Doppler-echocardiography: (1) end-diastolic left ventricular thickness and radius; (2) aortic pulse wave velocity; (3) mitral flow with measurement of early and late (atrial) peak velocities (E and A), pressure half-time and the velocity time integrals of the entire mitral curve and of the atrial wave; and (4) isovolumic relaxation time (i.e., the time between aortic closure and the mitral opening signals recorded simultaneously by continuous-wave Doppler). Heart rate and systolic blood pressure were not different in the 2 groups. Aortic pulse wave velocity and the wall thickness to radius ratio were significantly increased in the diabetic patients compared to the controls. E was significantly reduced whereas A/E, pressure half-time, the atrial contribution to the left ventricular filling (i.e., the ratio of the atrial velocity time integral to the mitral velocity time integral) and the isovolumic relaxation time were significantly increased in the diabetic group versus the control subjects. Lastly, 11 of 16 diabetic patients (69%) had at least 2 of the following abnormalities: A/E greater than 0.71, an atrial contribution to the left ventricular filling greater than 0.25, a pressure half-time greater than 50 ms and an isovolumic relaxation time greater than 88 ms. No correlations were found between the wall thickness to radius ratio, aortic pulse wave velocity and the filling indexes.(ABSTRACT TRUNCATED AT 250 WORDS)
Indexes of left ventricular diastolic filling were measured by radionuclide ventriculography in 28 patients with insulin-dependent diabetes mellitus without evidence of ischemic heart disease. Six patients (21%) had abnormal diastolic filling and differed from diabetic patients with normal filling in their greater severity of cardiac autonomic neuropathy, assessed by noninvasive means, and their lower plasma norepinephrine levels in the supine (131.1 +/- 24.7 versus 356.2 +/- 58.4 pg/ml, p less than 0.01) and upright (224.9 +/- 47.8 versus 673.3 +/- 122.3 pg/ml, p less than 0.005) positions. The diabetic patients determined as having cardiac autonomic neuropathy (n = 15) had depressed left ventricular diastolic filling compared with subjects free of autonomic neuropathy, whether measured as the time to peak filling rate (154.2 +/- 12.0 versus 119.1 +/- 10.6 ms, p less than 0.05) or the time to peak filling rate normalized to the cardiac cycle length (24.3 +/- 2.2 versus 16.2 +/- 1.5%, p less than 0.01). Of the various tests of autonomic nervous system function, the strongest correlate of impaired diastolic filling was orthostasis, measured as the decrease in systolic blood pressure with standing (r = 0.584, p less than 0.001). Thus, in patients with diabetes mellitus, alterations in sympathetic nervous system activity are associated with abnormalities of left ventricular diastolic filling.
Equilibrium radionuclide angiocardiography was performed on 19 men and 17 women with insulin-dependent diabetes mellitus (IDDM) and on 24 men and 15 women with noninsulin-dependent diabetes mellitus (NIDDM) and on 24 male and 24 female control subjects aged 46 to 67 years. All were without clinically evident cardiovascular disease. No significant differences were found in left ventricular (LV) ejection fraction at rest between men with IDDM (56 +/- 1%; mean +/- standard error of the mean) or NIDDM (58 +/- 1%) and control men (58 +/- 1%), whereas LV ejection fraction was higher in women with IDDM (63 +/- 1%; p less than 0.01) and NIDDM (64 +/- 2%; p less than 0.01) than in control women (58 +/- 1%). An abnormal LV ejection fraction response to dynamic exercise (an increase of less than 5% units or a decrease) was observed in 1 control man (4%), in 8 men with IDDM (42%, p less than 0.01) and in 10 men with NIDDM (42%, p less than 0.01). The respective figures were 4 (17%) for control women, 7 (44%, difference not significant) for women with IDDM and 10 (71%, p less than 0.01) for women with NIDDM. Abnormal LV ejection fraction response to exercise in diabetic patients was not related to the metabolic control of diabetes, presence of microangiopathy or abnormalities in the autonomic nervous function. Myocardial perfusion scintigraphy performed in 18 diabetic patients in whom LV ejection fraction decreased during exercise showed a reversible perfusion defect in only 5 (28%).(ABSTRACT TRUNCATED AT 250 WORDS)
Indexes of left ventricular diastolic filling were measured by pulsed Doppler echocardiography in 21 insulin-dependent diabetic patients and 21 control subjects without clinical evidence of heart disease. No patient had chest pain or electrocardiographic changes during exercise testing. The mean age of patients was 32 years. All patients had a normal ejection fraction. Six (29%) of the 21 diabetic patients had evidence of diastolic dysfunction as assessed by the presence of at least two abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in diabetic compared with control subjects (1.24 +/- 0.21 versus 1.66 +/- 0.30, p. less than 0.001). Atrial filling velocity was significantly increased in diabetic patients (74.3 +/- 16.7 versus 60.3 +/- 12.2 cm/s, p less than 0.004), whereas early filling velocity was reduced by a nearly significant degree (88.8 +/- 12.6 versus 98.5 +/- 18.8 cm/s, p less than 0.057). The atrial contribution to stroke volume as assessed by area under the late diastolic filling envelope compared to total diastolic area was also significantly increased in diabetic compared with control subjects (35 versus 27%, p less than 0.001). Left ventricular diastolic filling abnormalities in diabetic patients did not correlate with duration of diabetes, retinopathy, nephropathy or peripheral neuropathy. These data suggest that approximately one-third of such patients have subclinical myocardial dysfunction unrelated to accelerated atherosclerosis. Doppler echocardiography may offer a reliable noninvasive means to assess diastolic function and to follow up diabetic patients serially for any deterioration in cardiac status before the appearance of clinical symptoms.
To examine the relation of short- and long-term changes in glucose metabolism to cardiac function, radionuclide cineangiography and echocardiography were performed in 10 young insulin-dependent diabetic patients without clinical evidence of heart disease. Cardiac assessments were performed before and after both acute variations in blood glucose, and induction of chronic "tight glucose control" involving normalization of hemoglobin A1 concentrations. In diabetic patients, left ventricular (LV) ejection fraction (EF) at normal blood glucose concentration was indistinguishable from values in 11 normal subjects. However, during hyperglycemia (about 300 mg/dl), the average EF at rest was 61%, significantly higher than that during normoglycemia (56%, p less than 0.001). No significant change in LV diastolic dimension was noted in association with shifts between high and normal blood glucose concentrations. Normalization of hemoglobin A1 was achieved within 6 to 25 weeks. This alteration had no significant effect on LVEF, mitral valve E-F slope, or the response of systolic function to blood glucose levels. In addition, no correlation was found between LVEF and hemoglobin A1 concentrations in 4 of 5 evaluation periods. Thus, in young insulin-dependent diabetic patients without overt heart disease, variation in blood glucose concentration is associated with small but significant variation in EF at rest; normalization of hemoglobin A1 has no significant effect on LVEF or the response of systolic function to blood glucose levels.
Five simple, noninvasive cardiovascular reflex tests have been used to assess autonomic function in one center over the past 10 yr. Seven hundred seventy-four diabetic subjects were tested for diagnostic and research purposes. In 543 subjects completing all five tests, abnormalities of heart rate tests occurred in 40%, while abnormal blood pressure tests occurred in less than 20%. Their results were grouped as normal (39%), early (15%), definite (18%), and severe (22%) involvement. Six percent had an atypical pattern of results. Two hundred thirty-seven diabetic subjects had the tests repeated greater than or equal to 3 mo apart: 26% worsened, 71% were unchanged, and only 3% improved. The worsening followed a sequential pattern with first heart rate and later additional blood pressure abnormalities. Comparison between a single test (heart rate response to deep breathing) and the full battery in 360 subjects showed that one test alone does not distinguish the degree or severity of autonomic damage. These tests provide a useful framework to assess autonomic neuropathy simply, quickly, and noninvasively.
Cardiac function was investigated by echocardiography in 24 short-term Type 1 diabetic patients with a mean diabetes duration of 7 years (range 4-14 years) during conditions of ordinary metabolic control. Compared to 24 age and sex matched normal control subjects, measurements of myocardial contractility as left ventricular fractional shortening and mean circumferential shortening velocity were increased by 12% and 20% respectively. Another 8 Type 1 diabetic patients were examined during conditions of poor (hyperglycaemia and ketosis) and good metabolic control. Following improved glycaemic control, left ventricular fractional shortening and mean circumferential shortening velocity decreased by 16% and 24% respectively. Our findings show that short-term Type 1 diabetes is associated with increased myocardial contractility. Furthermore, this condition is related to the state of metabolic control.
The postmortem findings and clinical records of 27 patients with proved diabetic glomerulosclerosis were examined and reviewed for evidence of primary myocardial disease. Twenty-three cases were excluded because of complicating conditions such as hypertension, significant obstruction of the major coronary arteries or valvular disease. Four patients demonstrated cardiomegaly and congestive heart failure of no known cause.The autopsy findings consisted of left ventricular hypertrophy and, in 1 case, right ventricular hypertrophy as well, in the absence of major coronary artery disease. Histopathologic study revealed diffuse fibrotic strands extending between bundles of muscle fibers and myofibrillar hypertrophy. In 1 case, the small intramural coronary arterioles demonstrated thickening of the wall and narrowing of the lumen due primarily to the deposition of acid mucopolysaccharide material in the subendothelial layers and subsequent subintimal thickening and medial hypertrophy.It is postulated that the myocardial disease seen in these cases is probably secondary to diabetic mjcroangiopathy although the direct effects of the abnormal myocardial metabolism in diabetes could not be excluded.
Seventy three patients with idiopathic primary myocardial disease, 16 of whom had diabetes mellitus, were compared to matched patients without cardiomyopathy. A statistically significant increase was observed in the frequency of diabetes in patients with idiopathic cardiomyopathy. Evolution of cardiomyopathy in a patient with preexisting diabetes and angina pectoris was also established. Four diabetic patients died; autopsies were performed on three. In these patients, the large coronary arteries were patent and free of arteriosclerosis, but small vessel changes were present in the myocardium. In contrast, autopsy findings in 28 patients who had cardiomyopathy without diabetes showed small coronary vessel disease in only one patient. Diabetics can develop myocardial disease without large coronary artery involvement (diabetic cardiomyopathy), possibly due to pathologic changes in small coronary vessels.
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.
M-mode echocardiography was performed on 107 young insulin-dependent diabetic subjects aged 2-24 yr (mean +/- SE: 13.8 +/- 0.4 yr) and 636 age-group matched controls. All patients were normotensive and free of cardiorespiratory symptoms. Diabetic patients showed a high prevalence of echocardiographic abnormalities that increased with age. Mean dimensions of the left atrium, right ventricle, and left ventricle (systolic and diastolic) were increased significantly in diabetic individuals (P less than 0.01). Hypertrophy of the interventricular septum was present in some patients older than 12 yr of age. Mean interventricular septum excursion was markedly decreased in diabetic individuals compared with controls (3.9 +/- 0.1 mm versus 5.6 +/- 0.2 mm, respectively; P less than 0.01). Fifteen percent of the diabetic patients but none of the controls had septal excursions less than 3 mm (2 SD below mean). Patients with decreased septal excursions showed a higher prevalence of other echocardiographic abnormalities than patients with normal septal excursions. Echocardiographic abnormalities did not correlate with either duration of diabetes or glucose control as assessed by hemoglobin A1c and plasma glucose concentrations at the time of echocardiographic testing. The results show a high prevalence of echocardiographic abnormalities in young diabetic subjects that may represent preclinical cardiomyopathy.
Radionuclide ventriculographic studies were performed at rest and during exercise on 30 consecutive men, aged 21 to 35 years with diabetes mellitus without evidence of coronary artery or any other cardiovascular disease, and in 20 normal age-matched subjects. Sixteen (53%) were treated with insulin and 14 (47%) were treated with either diet (6 patients) or oral antidiabetic therapy (8 patients). All patients from both groups had normal left ventricular (LV) ejection fraction (EF) at rest. In 5 of the 30 diabetic patients (17%), LVEF decreased after exercise, in 8 (27%) it remained unchanged and in 17 it increased normally. Mean LVEF at rest and after exercise in this group was 66 +/- 7% and 72 +/- 7% (+/- standard deviation), respectively. In all normal subjects, LVEF increased after exercise. Mean LVEF at rest and after exercise in the normal group was 66 +/- 7% and 76 +/- 9%, respectively. No patient had evidence of regional dysfunction at rest or after exercise. LV function was not related to serum glucose levels during the test, modality of treatment, insulin dependency or duration of the disease. Three of 4 patients with diabetic microvascular complications showed LV dysfunction. In 4 of 5 patients in whom LVEF decreased after exercise, thallium studies showed normal perfusion. Thus, diabetes mellitus may cause exercise-induced global LV dysfunction in young men with no evidence of cardiovascular disease. This phenomenon apparently does not seem to follow the known course of diabetic microvascular complications.
To elucidate the mechanisms by which the new bipyridine inotropic agent milrinone improves cardiac function, we examined multiple indexes of left ventricular diastolic function before and after administration of milrinone to patients with advanced (NYHA class III or IV) congestive heart failure. In 13 patients left ventricular pressure measurements were made with a micromanometer to permit assessment of peak negative dP/dt and the time constant of left ventricular isovolumic relaxation, T, before and after milrinone. In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone. After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01). Left ventricular peak filling rate increased (1.2 +/- 0.6 to 1.7 +/- 0.7 end-diastolic volumes/sec; p less than or equal to .02) despite a decrease in left ventricular filling pressure (mean pulmonary wedge pressure 27 +/- 7 to 18 +/- 9 mm Hg; p less than .01). There was a fall in left ventricular end-diastolic pressure (28.6 +/- 6 to 19 +/- 7 mm Hg; p less than or equal to .01), with no significant change in left ventricular end-diastolic volume. This was associated with a downward shift in the left ventricular diastolic pressure-volume relationship in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
To assess left ventricular (LV) function in diabetes mellitus, M-mode echocardiograms were recorded in 36 insulin-treated diabetic women, mean age 25 +/- 6 (SD) years, and 13 healthy women of the same age. Echocardiographic tracings of the septum and LV posterior wall were digitized and continuous plots were made of LV dimension and its rate of change. The pattern of LV filling was abnormal in 19 diabetics, when the mean value +/- 2 SD in the healthy women was taken as the normal range of the indices. The most common abnormality was a prolonged rapid filling period. The LV systolic function was normal in all diabetics. Diabetics with severe microvascular complications had thicker LV walls (p less than 0.05) and smaller LV end-diastolic diameters and stroke volumes (p less than 0.01) than the healthy women. The electrocardiographic voltage was lower in the diabetic group (p less than 0.05). These studies suggest that minor abnormalities in LV function reflecting stiffness of the myocardium are common in young female diabetics, a patient group with a relatively low prevalence of coronary artery disease.
This study was undertaken to determine the prevalence and significance of diastolic left ventricular (LV) dysfunction in mild to moderate systemic hypertension. Rest and exercise equilibrium blood pool scintigraphy was performed in 39 hypertensive subjects (mean systolic blood pressure [BP] 156 +/- 14 mm Hg [+/- standard deviation]; mean diastolic BP 103 +/- 5 mm Hg) and 11 normal control subjects. These studies were analyzed for ejection fraction (EF), segmental wall motion, peak filling rate (PFR), time to PFR and filling fraction in the first third of diastole normalized for cycle length (first-third filling fraction). EF at rest was similar in the hypertensive patients and control subjects (0.63 +/- 0.09 versus 0.65 +/- 0.07); only 2 patients had a reduced EF. The EF response to exercise was normal in every hypertensive patient (increasing to a mean of 0.74 +/- 0.08); only 1 patient had asynergy. In contrast, even when the 2 patients with abnormal systolic function were excluded, each index of diastolic filling was significantly different from the control group. PFR was lower (2.29 +/- 0.49 vs 2.63 +/- 0.39 end-diastolic volumes per second [EDV/s], p less than 0.05), time to PFR was longer (199 +/- 47 versus 158 +/- 17 ms/s), p less than 0.01) and first-third filling fraction was smaller (0.38 +/- 0.11 vs 0.60 +/- 0.07, p less than 0.001). The latter index fell below the lowest normal value in 84% of the hypertensive patients. The degree of diastolic filling abnormality was not related to the patients' age, heart rate, BP, duration of systemic hypertension or systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular function at rest and during supine bicycle exercise was assessed by gated radionuclide angiography in 20 diabetic patients and 18 normal control subjects without clinical evidence of heart disease. The diabetic patients were aged 21 to 44 years and all except one used insulin. No subject developed chest pain or electrocardiographic changes during exercise. Both groups had a similar rest and exercise heart rate and blood pressure, and both achieved similar work loads. The control group had an ejection fraction at rest of 65.4 +/- 6.2% (mean +/- SD) and only 1 of 18 showed a decrease with exercise; peak exercise ejection fraction averaged 77.1 +/- 7.8%. The diabetic group had a mean ejection fraction at rest of 63.7 +/- 6.5%, similar to that of the control group, but 7 of 20 showed a decrease during exercise; the exercise ejection fraction averaged 67.7 +/- 9.7%, significantly lower than that of the control group (p less than 0.01). The diabetic patients varied widely in ejection fraction response to exercise, ranging from an increase of 25% to a decrease of 21%. This response did not correlate with age, sex, duration of diabetes, smoking, retinopathy, exercise heart rate, blood pressure or rate-pressure product, work load attained or ejection fraction at rest. These data suggest that approximately one-third of patients with diabetes have subclinical left ventricular dysfunction without correlation to risk factors for atherosclerosis or other diabetic complications. Whether this is due to unrecognized coronary artery disease or primary myocardial disease remains unknown.
We have shown a close relation between clinical microvascular complications and abnormalities of left ventricular function in 185 established diabetics without clinical heart disease. In 50 insulin-dependent diabetics who presented at under 20 years of age there was a correlation between the duration of diabetes and the isovolumic relaxation time, minimal dimension to mitral valve opening, and ratio of pre-ejection period to left ventricular ejection time. Diabetics with mild microvascular complications were similar to diabetics with no complications except for minor prolongation of the diastolic time intervals. Those with severe complications were significantly different from diabetes with milder complications and normal controls in all variables of left ventricular function. A close relation between left ventricular function and the microvascular complications index (code 0 when no complications to code 7 when all present and severe) was found for the following variables: isovolumic relaxation time, the interval from minimal dimension to mitral valve opening, ratio of pre-ejection period to left ventricular ejection time, and pre-ejection period index. It is concluded that in diabetes abnormalities of left ventricular function are related to duration of disease and complications; and that a diabetic specific heart muscle disorder occurs frequently in patients with severe microvascular complications.
Frequent abnormalities of left ventricular function were detected in 212 established diabetic patients using non-invasive techniques. Diabetics without angina or heart failure (n = 185) were significantly different from normal subjects (n = 50) in beat-to-beat variation, ratio of pre-ejection period to left ventricular ejection time, pre-ejection period index, isovolumic relaxation time, and interval from minimal dimension to mitral valve opening. Diabetics with angina (n = 18) were similar to control subjects with angina (n = 25); they showed a significant dimension change during the isovolumic period as compared with other diabetics and normals. Sixteen diabetics without angina also showed outward motion during the isovolumic period (incoordinate relaxation) and 13 had abnormal systolic time intervals. Four diabetics suffered a myocardial infarction during the study period; all had previously shown incoordination. Comparison of diabetics with a diastolic blood pressure below 100 mmHg and between 100 and 125 mmHg showed that the latter had a thicker posterior wall; the enlarged systolic dimension and reduced fractional shortening were the result of the inclusion of five of the 11 diabetic subjects with heart failure in the hypertensive group. Insulin-dependent diabetics tend to have more pronounced abnormalities of left ventricular function than those not requiring insulin. Patients selected from a diabetic clinic frequently have impaired left ventricular function, and ventricular hypertrophy, when present, in primarily caused by hypertension.
In order to study left ventricular diastolic function in diabetes mellitus, simultaneous echo- and phonocardiograms were recorded in 142 diabetics (free from heart disease), 20 normal subjects, and 16 patients with coronary artery disease. The resultant traces were digitised, and left ventricular relaxation and the rate and duration of cavity dimension increase and wall thinning were determined. Diastolic variables of left ventricular function were normal in 12 young diabetics with no complications. Significantly delayed mitral valve opening relative to minimum dimension and aortic valve closure was found in all other groups of diabetics. Forty-four diabetics with severe microvascular complications had significantly reduced peak rate and prolonged duration of wall thinning and dimension increase. The abnormalities were unlike those found in subjects with coronary artery disease. The extent of microvascular complications was significantly correlated to most variables of diastolic function. This relation was maintained in 31 diabetics with significant cavity dimension increase during isovolumic relaxation (incoordinate relaxation). In 42 juvenile onset patients there was good correlation between the duration of diabetes and most variables of diastolic function. These studies show that the primary cardiac abnormality in diabetic micro-angiography is a prolonged duration and reduced rate of posterior wall thinning with impaired left ventricular dimension increase, reflecting abnormal myocardial properties.
Cardiovascular effects of diabetic autonomic neuropathy include postural hypotension, resting tachycardia, and, possibly, painless myocardial infarction. Involvement of cardiovascular reflexes in diabetes can be assessed using simple noninvasive tests: the Valsalva maneuver, beat-to-beat heart rate variation, the heart rate response to standing, postural fall in blood pressure, and the sustained handgrip test. Tests of parasympathetic function appear to be abnormal more frequently and earlier in cardiac autonomic involvement, whereas sympathetic damage usually occurs later and is associated with clinical symptoms. When test results are abnormal, in association with symptoms suggestive of autonomic neuropathy, the prognosis is grave. Some sudden deaths that occur may be due to abnormal autonomic reflexes.
The use of heart rate monitoring in the diagnosis of diabetic autonomic neuropathy, and its value in observing the natural history of this disorder, has been assessed. Two tests were used: measurement of heart rate variation during deep breathing and of heart rate change on standing up. Two hundred and eighty seven diabetics aged between 20 and 49 years were studied, and 21 of them were observed repeatedly over 3 to 5 years. Heart rate variation (HRV) on deep breathing proved to be the more sensitive diagnostic index of autonomic neuropathy and was abnormal or borderline in 62 of 64 patients with established autonomic symptoms. Autonomic abnormalities were also detected in some diabetics without autonomic symptoms especially in those with peripheral neuropathy, 30% of whom had abnormal HRV on deep breathing. Abnormal tests appeared to represent permanent autonomic damage and may be present for years without the development of autonomic symptoms, occasionally (7%) preceding any other manifestation of diabetic neuropathy. Serial observations of HRV on deep breathing over 3 to 5 years showed little change, although overall there was a small deterioration of autonomic function, with a decrease of HRV score of 1.0 per year. The tests used are simple, and provide quantitative bedside measurements of autonomic function. When heart rate variation is normal, autonomic neuropathy is virtually excluded.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
The present study was designed to evaluate whether autonomic diabetic neuropathy is a marker of severe cardiovascular disease. We recruited three groups of 12 patients each with the same age, sex and body weight distribution: Group DAN + (diabetics with neuropathy), Group DAN- (diabetics without neuropathy) and Group C (healthy control group). The patients underwent two-dimensional color Doppler echocardiography and maximal electrocardiographic exercise test by cycloergometer (multistage program with 25 W increments 3 min steps). Cardiovascular autonomic function was evaluated by Ewing's tests (heart rate and blood pressure measurement during lying to standing, deep breathing, handgrip isometric stress test and Valsalva manoeuvre). Heart rate and blood pressure proved to be significantly higher in the Group DAN+, than in the other groups, either at baseline or during stress test. Only 33% of DAN+ patients proved to reach 100 W during stress test, compared to 82% of DAN- and 87% of control subjects. No DAN+ patients reached 125 W, compared with 45% of DAN- and 58% of Group C patients. Echocardiographic examination showed normal left ventricular systolic function in all groups, without any significant difference in ventricular dimensions, and impaired left ventricular diastolic function in DAN+ patients, compared to Group C subjects (peak E 66.75 +/- 8.36 vs 73.49 +/- 12.53 cm/s; peak A 72.1 +/- 13.42 vs 59.75 +/- 13.26 cm/s; E/A 0.84 +/- 0.21 vs 1.38 +/- 0.15 and isovolumetric relaxation time 101 +/- 21 vs 70 +/- 17 ms). Our data suggest that diabetic autonomic neuropathy is a marker of reduced exercise tolerance and of diastolic left ventricular dysfunction.
Disordini endocrini e della nutrizione e cardiopatie In: Braunwald E (ed) Trattato di medicina cardiovascolare, Vol II
- Ch Williams
- Braunwald
Atti del 25° Corso di Aggiornamento del Centro A. De Gasperi
- G Pozza
- S Chierchia
- A Margonato
- La
In: Braunwald E (ed) Trattato di medicina car-diovascolare
- Williams Ch E Braunwald
- Disordini
- L Della
- Irace
Williams CH, Braunwald E, Disordini endocrini e della nutrizi-one e cardiopatie. In: Braunwald E (ed) Trattato di medicina car-diovascolare, Vol II. Piccin Nuova Libraria, Padova, pp 1941-1970, 1985 L. Irace et al.: Left ventricular function in type 1 diabetes mellitus
Recommendation regarding quantitation in M-mode echocardiography: results of survey of echocardiographic measurements
- Dj Sahn
- De Maria
- A Kisslo
- J Weyman
Ventricular dysfunction in asymptomatic diabetics evaluated by rest equilibrium angiocardioscintigraphy
- C L Maini
- G Galli
- A Soricelli
- R Manna
- I Meloncelli
- M G Bonetti
- M G Pigini
- CL Maini
Echo-doppler study of left ventricular diastolic function in type I diabetes mellitus patients with and without autonomic neuropathy
- D Iarussi
- L Irace
- De Simone
- R Ruggiero
- B Giuliani
- F Armentano
- V Volpe
- Fp Iacono
Valutazione della presenza di neuropatia autonomica in diabetici asintomatici di tipo I e II
- V Manicardi
- E Bonora
- C Coscelli
- U Butturini
- F S Fein
- E H Sonnenblick
- Diabetic Cardiomyopathy
- FS Fein
Diabetic autonomic neuropathy
- J D Mackay
- Mcb Page
- J Cambridge
- JD Mackay
Improvement of indexes of diastolic performance in patients with congestive heart failure treated with milrinone
- E S Monrad
- R G Mckay
- D S Baim
- ES Monrad