Impaired cardiac adjustment to pregnancy in type I diabetes.

To assess the adaptation of the heart of diabetic subjects in the natural volume overload state of pregnancy, echocardiography was performed during each trimester and postpartum in 17 women with insulin-dependent diabetes mellitus (IDDM) and in 11 healthy women. The mean duration of diabetes was 14 yr and signs of microvascular complications were detected in 6 patients. The diabetic women had slightly smaller left ventricles than the control women already in the basal state (postpartum), and the pregnancy-induced increase in left ventricular size and stroke volume was less in the diabetic than in the control women. The heart rate rise also tended to be less in the diabetic women, resulting in a markedly smaller increase in cardiac output in this group (1.3 vs. 3.4 L/min, P less than .01). Left ventricular systolic function, wall thicknesses, or left atrial size did not differ between the groups at any point in the study. Minor collections of pericardial fluid were observed in 14 (76%) diabetic women and in 5 (45%) control women during the second and/or third trimester, but only 2 diabetic women had classic pericardial effusions. In conclusion, the normal hemodynamic adjustments to pregnancy seem to be impaired in women with IDDM. Preclinical diabetic cardiomyopathy and autonomic neuropathy may be involved in the observed alterations.

Augmentation of atrial contribution to left ventricular filling in IDDM subjects as assessed by Doppler echocardiography.

Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in 21 subjects (mean age 48 yr) with insulin-dependent diabetes mellitus (IDDM) and without evidence of ischemic heart disease and in 21 healthy control subjects of similar age and sex distribution. The peak mitral valve flow velocities during the early rapid filling phase (E) and during late atrial filling (A) were measured, and the ratio of these peak flow velocities (E:A) was calculated. E was similar in both groups, but A was higher (P less than .01) in the diabetic group. Thus, E:A was lower (1.19 +/- 0.24 vs. 1.65 +/- 0.67; P less than .01) in the diabetic subjects than in the control subjects. On subgroup analysis, 6 patients with cardiac autonomic neuropathy had lower E:A than the patients with no such disorder (0.99 +/- 0.15 vs. 1.29 +/- 0.25; P less than .05). E:A was not related to the duration of diabetes, presence of retinopathy, HbA1, or blood glucose levels. In conclusion, the atrial contribution to left ventricular filling seems to be augmented in diabetic subjects. This finding indirectly supports the view that left ventricular compliance is already reduced in asymptomatic diabetic subjects.

Autonomic influence on pregnancy outcome in IDDM.

We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy.

Effect of pregnancy on autonomic nervous function and heart rate in diabetic and nondiabetic women.

Supine and standing heart rate and heart rate responses to deep breathing and standing up (the 30-to-15 ratio), indices of autonomic nervous function, were measured during each trimester and postpartum in 25 women with insulin-dependent diabetes and 10 nondiabetic women. The groups did not differ with respect to autonomic function in the basal state (postpartum), and the heart rate response to deep breathing diminished progressively in both groups during pregnancy, although the change tended to be less pronounced in the diabetic women. The 30-to-15 ratio did not alter significantly during pregnancy. The diabetic women had a higher supine heart rate than the healthy women in the basal state, but the pregnancy-induced increase in heart rate was less in the diabetic women. Thus, the reversible diminution of heart rate response to deep breathing during pregnancy is a physiological finding and does not denote development of autonomic nervous dysfunction. Second, the increase in heart rate, a primary cardiovascular adjustment to pregnancy, seems to be blunted in diabetic women.

Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen.

OBJECTIVE: Non-enzymatic glycosylation of proteins occurs in diabetes and advanced glycosylated end products can accumulate in long lived proteins such as vascular collagen and reduce the elasticity of vessel walls. To evaluate the potential association of advanced glycosylated end products in collagen with diminished arterial elasticity in diabetes, 14 diabetic and 14 age and sex matched non-diabetic patients with coronary artery disease were studied. METHODS: Arterial elasticity was assessed in terms of carotid to femoral pulse wave velocity and by measuring the change in ascending aortic diameter induced by pulse pressure. Collagen linked fluorescence, a measure of advanced glycosylated end products, was determined from tissue specimens of the skin, ascending aorta, and right atrial appendage taken during coronary bypass surgery. RESULTS: As a sign of diminished arterial elasticity, carotid to femoral pulse wave velocity was raised (p < 0.01) and change in ascending aortic diameter tended to be diminished (p = 0.09) in the diabetic patients. Collagen linked fluorescence was increased (p < 0.05) in the myocardium of the diabetic group, but the difference in skin and aorta was not significant. Collagen linked fluorescence between the aorta, skin, and myocardium correlated with each other (r = 0.64-0.77). Collagen linked fluorescence in the aorta and myocardium correlated with carotid to femoral pulse wave velocity (r = 0.63 and r = 0.67, respectively) in the diabetic group but not in the control group. CONCLUSIONS: These data suggest that non-enzymatic glycosylation of matrix proteins, and specifically collagen, may modify arterial elasticity in diabetic patients with coronary artery disease.

Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

Effect of coronary artery bypass grafting on left ventricular response to isometric exercise.

The left ventricular (LV) response to isometric exercise was evaluated in 20 patients who performed handgrip exercise tests before and 3 months after coronary artery bypass grafting. Preoperative LV ejection fraction (EF) decreased during the handgrip test from 0.57 +/- 0.08 to 0.49 +/- 0.09 (p less than 0.001); the ratio between the LV peak systolic pressure (PSP) and end-systolic volume index (ESVI) did not change. In 12 patients with patent grafts, the LVEF after operation did not change (0.54 +/- 0.06 at rest and 0.56 +/- 0.06 during handgrip exercise) and PSP/ESVI ratio increased from 4.5 +/- 1.5 to 5.6 +/- 2.1 mm Hg/ml X m-2 (p less than 0.001) during exercise. In 8 patients with occluded grafts, the LVEF after operation decreased from 0.56 +/- 0.10 to 0.48 +/- 0.06 (p less than 0.02), whereas PSP/ESVI did not change during handgrip exercise. Thus, the LV response to isometric handgrip exercise appears to improve after coronary artery bypass grafting in patients with patent grafts, but not in patients with 1 or more occluded grafts.

Responses of heart rate variability to coronary occlusion during coronary angioplasty.

Signs of sympathetic activation are frequent during the early hours of anterior wall acute myocardial infarction, whereas parasympathetic reflexes predominate in inferior wall acute myocardial infarction. To assess the immediate autonomic responses to acute coronary occlusion, the high-frequency power and root-mean-square successive difference, frequency and time domain measures of heart rate (HR) variability were analyzed in 73 cases of significant (50 to 95%) coronary artery stenosis immediately before and during balloon occlusion (mean 99 seconds). The range of nonspecific changes was formed on the basis of a control group with no ischemia during dilatations of 16 totally occluded coronary arteries. Balloon occlusion of the left anterior descending artery (n = 35) caused an abnormal increase in the measures of HR variability as a sign of vagal activation in 8 patients (23%), and a significant decrease in HR variability in 4 (11%). Occlusion of the left circumflex artery (n = 19) caused an increase in HR variability in 5 patients (26%), and a decrease in 2 (11%). Right coronary artery occlusion (n = 19) caused an increase in HR variability in 5 patients (26%) and a decrease in 4 (21%). Thus, coronary occlusion causes immediate changes in HR variability in greater than one third of patients with coronary artery disease. The direction of these initial HR variability changes cannot be predicted by the site of coronary occlusion.

Circadian rhythm of heart rate variability in survivors of cardiac arrest.

Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 +/- 10 vs 51 +/- 15 ms, p less than 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 +/- 7 ms2 x 10 vs 28 +/- 14 ms2 x 10, p less than 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest.

Effect of preocclusion stenosis severity on heart rate reactions to coronary occlusion.

Autonomic mechanisms may have an important role in the clinical presentation of acute coronary occlusion. This research was designed to evaluate the effect of preocclusion stenosis severity on the immediate autonomic heart rate (HR) responses to a subsequent acute occlusion of the coronary artery. HR and its variability in the time and frequency domains were analyzed in patients with mild to moderate (< or = 85%) (group 1, n = 19) and severe (> 85%) (group 2, n = 18) left anterior descending coronary artery stenosis immediately before and during balloon occlusion (mean 108 seconds). The ranges of nonspecific responses were determined by analyzing HR reactions in a control group (n = 13) with no ischemia during balloon inflation of a totally occluded coronary artery. An abnormal increase in HR variability and/or bradycardia as a sign of vagal activation occurred in 6 patients (32%) in group 1 and in 3 patients (17%) in group 2. A significant decrease in HR variability or tachycardia, or both, was observed in 5 patients (26%) in group 1, but in none of the patients in group 2. Compared with the control group, the balloon occlusion of mild to moderate stenosis caused abnormal HR reactions more often than did occlusion of tight stenosis (58% vs 17%, p < 0.05). Balloon occlusions in group 1 caused chest pain (p < 0.01), ST-segment changes (p < 0.001), and narrowing of pulse pressure (p < 0.05) more often than did occlusions of severe stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting.

Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise-induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/- 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death.

Usefulness of a postoperative exercise test for predicting cardiac events after coronary artery bypass grafting.

The predictive value of a postoperative exercise test in terms of cardiac events after coronary artery bypass grafting (CABG) was prospectively studied in 231 consecutive patients. During a 5-year follow-up there were 28 cardiac events (12%), of which 15 were cardiac deaths (13 sudden), and 13 were nonfatal myocardial infarctions. There was no difference in the rate of graft patency between groups with and without cardiac events, but ejection fraction was lower in patients with than without events (51 +/- 16% vs 58 +/- 10%; p less than 0.05). Duration of the exercise test was shorter, and maximal work load was lower in patients with cardiac events (p less than 0.05 for both). The prevalence of greater than or equal to 1 mm ST-segment depression was 22% (symptomatic in 25%, and silent in 75%) and did not differ between groups with and without cardiac events. After adjustment for prognostic variables using the proportional hazards method, diuretic treatment (p = 0.007) and a low postoperative ejection fraction (p = 0.04) remained significant for predicting the risk of cardiac events within 5 years of CABG, but exercise duration and work load did not have any significant predictive value. Thus, the predictive value of a postoperative exercise test is limited, and signs of impaired left ventricular function are of greater significance for the 5-year prognosis after CABG than are those of myocardial ischemia.

Changes in frequency domain measures of heart rate variability in relation to the onset of ventricular tachycardia in acute myocardial infarction.

The imbalance of the autonomic nervous function has been shown to contribute to the genesis of ventricular arrhythmias. Power spectral analysis of components of heart rate variability has the potential to quantify the cardiac autonomic tone during ambulatory electrocardiographic recording. We analysed the power spectral components of total power, very low frequency power (0.0033-0.04 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power in 12 consecutive patients accompanied with 27 episodes of ventricular tachycardia in acute myocardial infarction. The spectral areas were measured in 5-min periods preceding the onset of ventricular tachycardias. The total power of heart rate variability increased progressively before the onset of ventricular tachycardia episodes (P < 0.05). The increase of total power was mainly due to higher, very low frequency power at the onset rather than before the onset of ventricular tachycardia (P < 0.05). The trend towards adrenergic predominance at the onset of ventricular tachycardia was observed by an increase of average heart rate (P < 0.05) without concomitant increase in high frequency power. Thus, the occurrence of ventricular tachycardia is associated with changes in the power spectrum of heart rate variability suggesting alterations in autonomic tone at the onset of ventricular tachycardia in acute myocardial infarction.

Circadian variation of ventricular tachycardia in patients with coronary arterial disease.

Sudden cardiac death and ischaemic cardiac events occur in a circadian pattern. Because ventricular tachycardia is thought to play an important role in sudden cardiac death, the episodes of spontaneous ventricular tachycardias (greater than 3 consecutive beats) (n = 1314) were analysed from 24-hour long term electrocardiographic recordings in 34 patients with coronary arterial disease to determine whether circadian rhythm exists in spontaneous ventricular tachycardia. Twelve patients had suffered cardiac arrest, four patients had a history of syncope, and palpitation was the indication for electrocardiographic recordings in eighteen patients. Analysis using chronobiologic single cosinor method showed a significant circadian variation in the occurrence of ventricular tachycardia episodes with the peak occurring at 6 a.m. Similar circadian rhythm was also observed in the occurrence of the longest episode of ventricular tachycardia. Ischaemic ST-segment depression preceded the longest ventricular tachycardia episode only in one patient. Thus, a circadian rhythm occurs also in spontaneous episodes of ventricular tachycardia, a finding which is similar to that in sudden cardiac death.

Impaired parasympathetic control of heart rate after myocardial infarction.

We measured the variation in heart rate during deep breathing, a sensitive non-invasive measure of cardiac parasympathetic activity, in 95 patients 3 weeks after myocardial infarction and in 40 asymptomatic healthy controls. The variation in rate was significantly lower (11.6 +/- 6.1 vs 17.6 +/- 7.3 beats/min, P less than 0.001) in patients with myocardial infarction than in controls. Forty-nine patients (52%) and 5 controls (13%) were considered to have diminished (less than or equal to 10 beats/min) variation of rate. The diminution in this variation was not related to the type or location of myocardial infarction, to maximum release of CK-MB or to cardiovascular medication. Our results suggest that impairment of vagal control of heart rate is common after myocardial infarction. The impairment cannot be predicted by any specific feature of the disease.

Prevalence and prognostic significance of complex ventricular arrhythmias after coronary arterial bypass graft surgery.

To assess the prevalence and long-term prognostic significance of complex ventricular arrhythmias after coronary arterial bypass graft surgery, 126 patients were studied by 24-hour ambulatory electrocardiographic recordings and cardiac catheterizations (including left ventricular, coronary arterial and bypass graft angiograms) before and 3 months after surgery, and then prospectively followed-up for a mean of 50 months. Complex ventricular arrhythmias (ventricular premature complexes greater than 30/hour, multiform and/or repetitive complexes) occurred more commonly after than before surgery (in 49/126 vs. 30/126 patients, P less than 0.05). In 18 patients (14%) who had significant worsening of ventricular arrhythmias, the ejection fraction decreased significantly (from 56 +/- 13% to 50 +/- 15%, P less than 0.05) after operation. During the period of follow-up, there were 4 witnessed sudden cardiac deaths. Complex ventricular arrhythmias tended to be more prevalent in patients who died suddenly (in 100%) compared to survivors (in 37%), but their presence did not predict the subsequent sudden death when ejection fraction was included in the stepwise regression model. None of the patients with an ejection fraction over 40% suffered sudden death despite the prevalence of complex arrhythmias in 32% of these patients. Thus, complex ventricular arrhythmias tend to occur more frequently after than before bypass surgery and their occurrence appears to be related to impairment of left ventricular function. Patients with well preserved ventricular function are at low risk of dying suddenly despite presence of complex ventricular arrhythmias after surgery.

Effect of coronary arterial occlusion on vagal control of heart rate.

Diminished variation in heart rate as a sign of impaired vagal control is common in coronary arterial disease. To evaluate the effect of short-term myocardial ischaemia induced by coronary arterial occlusion during therapeutic percutaneous transluminal coronary angioplasty we measured the variation in heart rate during controlled deep breathing in 50 patients before and during arterial occlusion. Variation in heart rate diminished from 11.1 +/- 4.5 to 9.5 +/- 5.1 beats/min (P less than 0.01) during occlusion. No change occurred in heart rate, blood pressure or levels of noradrenaline and adrenaline. The attenuation of variation in the heart rate was not significantly associated with the site or duration of arterial occlusion nor concomitant chest pain. Thus, brief coronary arterial occlusion seems to be associated with impairment of the vagal control of heart rate in patients with coronary arterial disease.

Asymptomatic coronary artery disease in diabetes: relation to common risk factors, lipoproteins, apoproteins and apo E polymorphism.

The risk factors for asymptomatic coronary artery disease (CAD) were examined in 138 diabetic patients. Following non-invasive screening examinations (exercise electrocardiography, dynamic thallium scintigraphy, 24-h electrocardiographic recording), CAD was confirmed angiographically in 21 symptom-free diabetic subjects with an ischaemic finding in at least one of the non-invasive tests. The prevalence of asymptomatic CAD in this cohort of diabetic patients was 21/132 (16%), which may be an underestimation because 6 patients refused angiography. Risk factors (age, diabetes, smoking, hypertension, serum lipoproteins, apoproteins and apo E phenotypes) were analysed according to the presence or absence of CAD. Multivariate logistic stepwise analysis did not show any definite changes of serum lipids, lipoproteins and apoproteins in type 1 (n = 72) and type 2 (n = 66) diabetic patients with or without asymptomatic CAD. The only factors associated with asymptomatic CAD were the duration of diabetes (P < 0.005) and the age of the patient (P < 0.05). These results suggest that in diabetic patients the major risk factor for premature coronary atherosclerosis is diabetes itself. Assessment of other risk factors does not seem to define any subgroup with asymptomatic CAD.

Asymptomatic coronary artery disease in diabetes: associated with autonomic neuropathy?

To elucidate the potential association of diabetic autonomic neuropathy with increased prevalence of silent coronary artery disease (CAD), 138 asymptomatic diabetic subjects were screened using exercise ECG. 24-h ambulatory ECG and dynamic thallium scintigraphy. Fourteen patients with exercise-induced myocardial ischaemia and angiographically confirmed CAD (greater than or equal to 50% coronary artery narrowing) were found using this protocol. Their autonomic nervous function was assessed using standard cardiovascular tests and compared with that of 23 consecutive diabetic patients catheterised because of symptomatic CAD (mean New York Heart Association class 3.0). The diabetic patients with symptomatic CAD had more severe coronary atherosclerosis than the diabetic patients with asymptomatic CAD assessed by jeopardy score (P less than 0.01). The groups did not, however, differ with respect to autonomic function tests. Five patients (22%) with symptomatic CAD and 3 patients (21%) with asymptomatic CAD had definite autonomic dysfunction, i.e. two or more abnormal tests. Thus, our results suggest that the frequency of autonomic neuropathy is not increased in diabetic patients with asymptomatic CAD. The contribution of diabetic autonomic neuropathy to the absence of cardiac pain needs further clinical and pathological studies.

The relationship of ventricular arrhythmias to the angiographically and scintigraphically estimated extent of ventricular damage late after myocardial infarction.

In order to study the quantitative relationship of ventricular arrhythmias to myocardial damage and ischemia, 61 patients with a previous myocardial infarction (at least 6 months previously) were studied by 24-hour ambulatory ECG monitoring, cardiac catheterization, and thallium-201 scintigraphy. Thirty-five patients (57%) had no ectopic beats or only infrequent, unifocal ones and 26 patients (43%) had complex ventricular arrhythmias. Left ventricular function was lower in the latter (p less than 0.05), but the number of diseased vessels did not differ in the two groups. The reduction of thallium activity in the infarct area was more marked in patients with complex arrhythmias (p less than 0.001). Multiple thallium defects were not more common in arrhythmia patients, however. These data support the view that complex ventricular arrhythmias are more closely related to the severity of ventricular damage than the presence of myocardial ischemia remote to the area of previous infarction.