Mitochondrial DNA deletions in dilated cardiomyopathy: a clinical study employing endomyocardial sampling.

OBJECTIVES: The aim of this study was to assess the occurrence of the two most commonly encountered mitochondrial DNA (mtDNA) deletions in the hearts of patients with idiopathic dilated cardiomyopathy. BACKGROUND: The mutation frequency of mtDNA is high, and sporadic cases of cardiomyopathies associated with mtDNA deletions have been described. Reports of increases in mtDNA deletions with advancing age also exist. METHODS: We studied 15 consecutive patients with typical signs of idiopathic dilated cardiomyopathy, without a family history, together with 16 control hearts obtained at autopsy from patients who died of noncardiac causes. The patients underwent both right and left heart catheterization, during which endomyocardial biopsy samples were taken. The mtDNA in these samples and in the control hearts was analyzed by the polymerase chain reaction technique for the occurrence and proportion of 5- and 7.4-kilobase (kb) deletions (Cambridge sequence map positions from nucleotides 8469 to 13447 and 8637 to 16084, respectively). RESULTS: The 5-kb mtDNA deletion was observed in the hearts of all of the patients with idiopathic dilated cardiomyopathy, accounting for 0.32 +/- 0.05% (mean +/- SEM) of the total mtDNA. The 7.4-kb deletion was found in 7 of the 15 patients with idiopathic dilated cardiomyopathy and comprised 0.28 +/- 0.08% of the total. The 5- and 7.4-kb deletions were detected in 12 and 9 control hearts, respectively, quantitatively similar to the patients with idiopathic dilated cardiomyopathy. A sigmoidal age dependency of the mtDNA deletions was found both in the patients with cardiomyopathy and in the control hearts, but after elimination of the confounding age variable, there was no difference between these groups. CONCLUSIONS: Because of the similarity of the age-dependent increase in the frequency of mtDNA deletions in cardiomyopathic and control hearts, the deletions have no causal relation with idiopathic dilated cardiomyopathy. The present results confirm the notion of an increase in mtDNA deletions with advancing age and show that endomyocardial tissue sampling is a feasible method for detecting mtDNA defects in affected hearts.

Gender difference in autonomic and hemodynamic reactions to abrupt coronary occlusion.

OBJECTIVES: We sought to determine whether there are gender-related differences in autonomic and hemodynamic responses to abrupt coronary occlusion. BACKGROUND: The risk of sudden death before hospital admission is higher in men with an acute myocardial infarction. The reasons for this gender-related difference are not well understood. Cardiovascular autonomic regulation modifies the outcome of acute coronary events, and there are gender differences in the autonomic regulation of heart rate (HR) in normal physiologic circumstances. METHODS: We analyzed the changes in HR, HR variability and blood pressure and the occurrence of ventricular ectopic beats during a 2-min coronary occlusion in 140 men and 65 women referred for single-vessel coronary angioplasty. The ranges of nonspecific responses were determined by analyzing a control group of 19 patients with no ischemia during a 2-min balloon inflation in a totally occluded coronary artery. RESULTS: Women more often had ST segment changes (p < 0.01) and chest pain (p < 0.05) during the occlusion. Significant bradycardia or increase in HR variability as a sign of vagal activation occurred more often in women than in men (31% vs. 13%, p < 0.01 and 25% vs. 11%, p < 0.05, respectively). Coronary occlusion also more often caused (28% vs. 11%, p < 0.01) a decrease in blood pressure in women. The most pronounced female preponderance was in the incidence of Bezold-Jarisch-type reaction (i.e., simultaneous bradycardia and decrease in blood pressure [16% vs. 0.7%, p < 0.0001]). Logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia identified female gender to be an independent predictor of bradycardic reactions (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.7, p < 0.01), hypotensive reactions (OR 2.6, 95% CI 1.1 to 6.0, p < 0.05) and Bezold-Jarisch-type response (OR 22.2, 95% CI 2.5 to 200, p < 0.01). Significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats emerged as having borderline significance (OR 0.4, CI 0.1 to 1.1, p = 0.07). CONCLUSIONS: Vagal activation is more common in women than in men during abrupt coronary occlusion and may have beneficial antiarrhythmic effects, modifying the outcome of acute coronary events.

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.

Effect of coronary artery disease on parasympathetic cardiovascular reflexes in NIDDM patients.

To evaluate the effect of coronary artery disease on parasympathetic cardiac reflexes in patients with non-insulin-dependent diabetes mellitus (NIDDM), we studied standard cardiovascular reflexes in 27 NIDDM patients with coronary artery disease (group 1) and in 21 NIDDM patients with no signs of coronary artery disease (group 2). Groups did not differ with respect to age, duration of diabetes, or presence of retinopathy. The mean +/- SD heart-rate variation in deep breathing was lower in group 1 than in group 2 (11.6 +/- 6.5 vs. 17.1 +/- 9.0 beats/min, P less than 0.05). Heart-rate variation was more often abnormally low (less than or equal to 10 beats/min) in group 1 than in group 2 (48 vs. 19%, P less than 0.05). Thus, the presence of coronary artery disease appears to modify cardiac parasympathetic reflexes in patients with diabetes mellitus and must be kept in mind when interpreting test results.

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.

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.

Dispersion of the QT interval and autonomic modulation of heart rate in hypertensive men with and without left ventricular hypertrophy.

Left ventricular hypertrophy is an independent risk factor for sudden cardiac death in hypertension, but the mechanisms of electrical instability associated with hypertrophy are not well known. We studied dispersion of the QT interval, an index of inhomogeneity of repolarization, and heart rate variability, a measure of cardiac autonomic modulation, in a randomly selected population of 162 men with systemic hypertension and made comparisons between the patients with echocardiographic evidence of left ventricular hypertrophy (left ventricular mass index > or = 131 g/m2, n = 44) and those without hypertrophy (left ventricular mass index < 131 g/m2, n = 118). The heart rate-corrected QT dispersion (67 +/- 37 versus 53 +/- 21 milliseconds, P < .05) and QT apex dispersion (55 +/- 22 versus 44 +/- 16 milliseconds, P < .01) were significantly longer in the patients with left ventricular hypertrophy than in those without hypertrophy. Thirteen of the 44 patients (30%) with hypertrophy versus 7 of the 118 patients (6%) without hypertrophy had an abnormally long QT apex dispersion ( > 70 milliseconds) (P < .001). The time and frequency domain measures of heart rate variability did not differ significantly between the patient groups with and without left ventricular hypertrophy. The measures of heart rate variability were not related to QT dispersion or left ventricular mass index but had a negative correlation with blood pressure values (eg, r = -.30 between the low-frequency component of heart rate variability and systolic pressure, P < .001). Age, body mass index, antihypertensive medication, and the other demographic variables were similar between the groups, but the patients with left ventricular hypertrophy had higher systolic (P < .01) and diastolic (P < .01) pressures compared with the patients without hypertrophy. Left ventricular hypertrophy in hypertensive men is associated with inhomogeneity of the early phase of ventricular repolarization, favoring susceptibility to reentrant ventricular tachyarrhythmias. Abnormalities in cardiac autonomic function, which may trigger a spontaneous onset of arrhythmias, are related to elevated blood pressure but not specifically to left ventricular hypertrophy.

Noninvasive evaluation of the athletic heart: sprinters versus endurance runners.

To evaluate possible differences in the cardiac effects of different types of running training, 22 competing male runners--10 sprinters and 12 endurance runners--were studied with a physical examination, electrocardiography, chest X-ray film and echocardiography. Thirteen sedentary men served as control subjects. There were no differences between the athletic groups in physical findings. However, left ventricular hypertrophy in the electrocardiogram was more apparent in the endurance runners (P less than 0.05), whose relative heart size on chest X-ray examination was also greater than in the sprinters (P less than 0.02). On echocardiography the left ventricular end-diastolic volume was equally greater than normal in both groups of athletes (P less than 0.005), but in the endurance runners the percent chance of the minor axis diameter in systole was greater than in the sprinters or control subjects (P less than 0.02). Values for left ventricular wall thickness and mass were greater than normal in both groups of athletes but were higher in the endurance runners than in the sprinters (P less than 0.001). The left atrial diameter was apparently greater in the endurance runners than in the sprinters or control subjects (P less than 0.001), whereas that of the sprinters did not differ from normal. Thus, intensive sprinter training seems to dilate the left ventricle but causes less increase in wall thickness and mass than training for endurance running and no change in left ventricular function or left atrial size. Endurance running causes left ventricular dilatation equal to that of sprinter training, greater wall hypertrophy and improved systolic emptying of the left ventricle, and it also dilates the left atrium perhaps because of decreased left ventricular compliance.

Stenosis severity and the occurrence of ventricular ectopic activity during acute coronary occlusion during balloon angioplasty.

To elucidate the incidence and determinants of early ventricular arrhythmias (VA) during acute coronary occlusion, continuous electrocardiographic, heart rate, and blood pressure recordings were performed in 152 patients during standardized balloon occlusions of significant (50% to 95%) coronary artery stenoses. A control group of 13 patients with chronic total occlusion of a coronary artery was also studied. None of them developed VA during balloon inflation in the preexisting total occlusion of the artery. Balloon occlusion of a coronary artery was associated with occurrence of ventricular ectopy in 18 patients (VA group, 12%). The VA group had milder stenosis severity (72% vs 81%, p < 0.001) than the rest of the patients, and none of them had visible collaterals to the occluded vessel. The VA group also had ST-segment deviations more often (p < 0.05) during occlusion than patients with no VA. Occlusion of the left anterior descending artery caused VA more often (p < 0.05) than occlusion of the left circumflex or right coronary artery. No clinical or hemodynamic variable or medication was associated with the occurrence of VA. In stepwise logistic regression analysis, the only significant predictors of ventricular ectopic activity were the stenosis severity and the anterior site of coronary occlusion. Even a nonstenotic plaque can be so fragile that it is prone to rupture. The present findings suggest that such an occlusion may result in electrical instability more easily than occlusion of a more advanced coronary lesion.

Detection of coronary artery disease by thallium imaging using a combined intravenous dipyridamole and isometric handgrip test in patients with aortic valve stenosis.

Detection of coronary artery disease (CAD) in patients with aortic valve stenosis (AS) is clinically difficult. Thallium-201 images were generated in 27 patients with AS during combined intravenous dipyridamole and handgrip test, which induces a marked acute increase in coronary blood flow. Isolated AS was noted in 21 patients and combined AS and aortic regurgitation in 6. Thirteen patients had more than 50% diameter stenosis in 1 or more coronary arteries on angiography. Eleven of them had reversible perfusion defects on post-stress thallium scans (sensitivity 85%). Two patients had thallium defects without angiographic evidence of significant CAD (specificity 86%). In the other 12 patients with normal coronary angiographic findings, the thallium scans were normal. Two patients had dizziness and hypotension after dipyridamole infusion, which disappeared during the handgrip test; 2 others had chest pain during handgrip. One of them was treated with aminophylline and the other with aminophylline and nitroglycerin. No other adverse effects were reported by the patients and no major complications occurred during stress testing. Thus, thallium imaging during combined intravenous dipyridamole and handgrip test appears to be a promising noninvasive method of revealing CAD in patients with AS.

Prevalence and significance of gallium-67 uptake in the heart after open-heart surgery.

Radioactive gallium-67 (Ga-67) has been shown to accumulate within areas of pericardial inflammation. The present study estimated prospectively the prevalence and clinical significance of Ga-67 uptake in the heart in 62 patients 10 to 16 days after open-heart surgery. Of 62 patients studied, markedly diffuse Ga-67 uptake was detected in 21 (34%) and focal or mild diffuse uptake in 23 (37%). Results were negative in 18 (29%). Nine patients with a negative scan result (50%) had received corticosteroid therapy before imaging, whereas only 2 patients with a positive scan result (5%) were receiving steroids. The erythrocyte sedimentation rate and C-reactive protein level were both higher in patients with Ga-67 uptake compared with those with a negative scan result (p less than 0.01 in both). No other clinical, echocardiographic or electrocardiographic indicators of postpericardiotomy syndrome were related to Ga-67 uptake. No patient developed cardiac tamponade or constrictive pericarditis during the 12-week follow-up and the Ga-67 scan results did not predict the occlusion of coronary artery bypass grafts. Thus, pericardial inflammation manifested as Ga-67 uptake is a common finding after open-heart surgery and appears to be a benign condition.

Comparison of dipyridamole-handgrip test and bicycle exercise test for thallium tomographic imaging.

Seventy-three patients with angina pectoris and 20 with atypical chest pain, who underwent coronary angiography, were examined by single-photon emission computed thallium tomography (TI-SPECT) using a combined dipyridamole-handgrip stress test. Perfusion defects were detected in 78 of 81 patients with angiographically significant coronary artery disease (CAD) (sensitivity 96%). In 9 of 12 patients without CAD, the thallium images were normal (specificity 75%). Thirty-five patients with CAD were reexamined by TI-SPECT using a dynamic bicycle exercise stress test. The sensitivity of the dipyridamole-handgrip test did not differ from the bicycle exercise test in diagnosing the CAD (97% vs 94%). Multiple thallium defects were seen in 19 of 22 (86%) patients with multivessel CAD by the dipyridamole-handgrip test but only in 14 of 22 (64%) by the bicycle exercise test. Noncardiac side-effects occurred in 17 of 93 (18%) patients after dipyridamole infusion. Cardiac symptoms were less common during the dipyridamole-handgrip test than during the bicycle exercise (15% vs 76%, p less than 0.01). These data suggest that the dipyridamole-handgrip test is a useful alternative stress method for thallium perfusion imaging, particularly in detecting multivessel CAD.

Left ventricular response to isometric exercise and its value in predicting the change in ventricular function after mitral valve replacement for mitral regurgitation.

Reduced left ventricular (LV) afterload and its effect on the resting ejection fraction may lead to overestimation of LV function in mitral regurgitation (MR). To evaluate LV function during increased afterload of the heart, an isometric handgrip test was performed during cardiac catheterization in 15 patients with mitral regurgitation (MR group) and in 9 normal subjects (normal group). Twelve months after successful mitral valve replacement (MVR) the patients were recatheterized, and the value of preoperative stress testing in predicting the change in resting ventricular function after surgery was estimated. Isometric exercise caused an increase in endsystolic wall stress, a measure of ventricular afterload, in both the MR group and the control group (p less than 0.001). The ejection fraction remained unchanged in the control group, but decreased from 0.58 +/- 0.08 to 0.53 +/- 0.08 in the MR group (p less than 0.001). After MVR, end-systolic wall stress increased significant (p less than 0.001) and the ejection fraction decreased from 0.58 +/- 0.05 to 0.51 +/- 0.1 (p less than 0.05). A positive correlation existed between the change in the ejection fraction during preoperative stress testing and the change in the resting ejection fraction after MVR (r = 0.65, p less than 0.01). In 8 patients whose resting ejection fraction was within normal limits (greater than 0.55) preoperatively, the ejection fraction was depressed (less than 0.55) 1 year after surgery. In all but 1 of these patients the isometric exercise revealed the reduced ventricular response to afterload stress preoperatively (decrease of the ejection fraction greater than 0.03 during exercise). Therefore, the isometric exercise-induced change in LV function appears to predict the influence of MVR on LV function.

Heart rate variability during repeated arterial occlusion in coronary angioplasty.

Acute coronary occlusion may cause severe autonomic reactions that can modify the clinical presentation of acute ischemic events. To evaluate whether adaptation in these autonomic reactions exists during repeated short coronary occlusions, heart rate (HR) and its variability in the time and frequency domains were analyzed in 70 patients with significant (50% to 95%) coronary artery stenosis immediately before and during 2 identical balloon occlusions of the vessel (mean 110 seconds). Reactions were compared with the range of nonspecific changes formed by analyzing a control group (n = 13) with no ischemia during balloon inflation in a totally occluded coronary artery. Thus, neither occlusion caused significant changes in HR or HR variability in 29 patients (41%). Vagal activation, as seen by an abnormal increase in HR variability or bradycardia, or both, was observed in 24 patients (34%). HR reactions in this group (p < 0.05) were significantly attenuated during the second occlusion. An opposite reaction (i.e., abnormal decrease in HR variability or tachycardia, or both) was observed in 17 patients (24%). A nonsignificant tendency for attenuation of the reactions was also seen in this group. Severity of chest pain, frequency of ST-segment shifts, or narrowing of pulse pressure were comparable during the 2 occlusions. Thus, a preceding short vessel occlusion-reperfusion cycle seems to attenuate autonomic HR reactions, especially vagal reactions, during subsequent coronary occlusion. Alleviation of extreme autonomic reactions may modify the clinical outcome of coronary occlusion in a beneficial way.

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.

Baroreflex sensitivity in drug-treated systemic hypertension.

Baroreflex sensitivity is impaired in patients with systemic hypertension. The persistence of abnormal baroreflex sensitivity despite adequate blood pressure control may be one of the reasons why the effect of antihypertensive therapy on coronary artery disease mortality has been less than expected on the basis of the achieved blood pressure levels.

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.

Heart rate variability in systemic hypertension.

Low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-standing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain measures of HR variability were compared in randomly selected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 +/- 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normotensive ones (52 +/- 19 vs 59 +/- 20 mss; p <0.01), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p <0.001 for both). Hypertensive subjects also had blunted changes of the normalized low- and high-frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p <0.001 for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the patients with hypertension (beta--0.20, p=0.01) and in the normotensive subjects (beta--0.28, p=0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normotensive controls. These data show that long-standing hypertension results in reduced overall HR variability and blunted autonomic responses to a change in body posture. Altered autonomic modulation of HR in hypertension is mainly due to elevated blood pressure and obesity in males with long-standing hypertension as compared with normotensive subjects.

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.