Effect of essential hypertension on cardiac autonomic function in type 2 diabetic patients.

OBJECTIVES: The aim of this study was to examine the effects of essential hypertension on cardiac autonomic function in type 2 diabetic patients. BACKGROUND: Hypertension is common in type 2 diabetic patients and is associated with a high mortality. However, the combined effects of type 2 diabetes and essential hypertension on cardiac autonomic function have not been fully elucidated. METHODS: Thirty-three patients with type 2 diabetes were assigned to a hypertensive diabetic group (n = 15; age: 56 +/- 8 years, mean +/- SD) or an age-matched normotensive diabetic group (n = 18, 56 +/- 6 years). Cardiac autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability (HRV), plasma norepinephrine concentration and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.05). The early and delayed myocardial uptake of 123I-MIBG was lower (p < 0.01 and p < 0.05, respectively), and the percent washout rate of 123I-MIBG was higher (p < 0.05) in the hypertensive diabetic group. However, the high frequency (HF) power and the ratio of low frequency (LF) power to HF power (LF/HF) of HRV and plasma norepinephrine concentration were not significantly different. The homeostasis model assessment index was higher in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.01). CONCLUSIONS: Our results indicate that essential hypertension acts synergistically with type 2 diabetes to depress cardiac reflex vagal and sympathetic function, and the results also suggest that insulin resistance may play a pathogenic role in these processes.     

Effect of glycemic control on heart rate variability in type I diabetic patients with cardiac autonomic neuropathy.

Diabetic cardiac autonomic neuropathy (CAN) is associated with a high risk of cardiovascular events. Previous studies have shown that strict glycemic control slows the deterioration of CAN as assessed by standard autonomic function tests but fails to show reversibility. The aim of this study was to evaluate the effect of glycemic control on early and advanced CAN in type I diabetic patients using power spectral analysis of heart rate variability (HRV). Ten patients with early and 13 patients with advanced CAN were enrolled in a program of intensified insulin treatment. Standard autonomic function tests and 24-hour time and frequency domain HRV parameters were obtained at baseline, 3, 6, and 12 months. Hemoglobin A1C decreased from 9.5 +/- 0.4% to 8.4 +/- 0.5% (p = 0.02) in the early CAN group, and from 9.3 +/- 0.4% to 8.2 +/- 0.5% (p = 0.006) in the advanced CAN group. In general, both time and frequency domain HRV indexes tended to improve in patients with early CAN but continued to deteriorate in patients with advanced CAN. The low- and high-frequency power increased in patients with early CAN (229 +/- 95 to 626 +/- 563 ms2 and 62 +/- 30 to 183 +/- 168 ms2, respectively). The high-frequency power significantly improved at 12 months over baseline (p = 0.04), indicating increased parasympathetic tone. By contrast, these parameters continued to deteriorate in patients with advanced CAN (65 +/- 32 to 46 +/- 8 ms2 and 193 +/- 75 to 144 +/- 33 ms2, respectively). Autonomic function tests showed no significant change in both groups. These data show that a reversible metabolic component of CAN exists in patients with early CAN. Power spectral analysis of HRV allows early identification of potential reversibility as early as 1 year after the institution of strict glycemic control.     

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure

OBJECTIVES: The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV). BACKGROUND: In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited. METHODS: Nineteen consecutive patients with moderate, stable CHF (age 54 +/- 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 +/- 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age +/- 3 years, same NYHA class, LVEF +/- 3%, pulmonary wedge pressure +/- 3 mm Hg, peak volume of oxygen +/- 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months. RESULTS: Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 +/- 0.4 vs. 1.8 +/- 0.5, p < 0.01), systolic and diastolic function (LVEF 23 +/- 7 vs. 28 +/- 9%, p < 0.01; pulmonary wedge pressure 17 +/- 8 vs. 14 +/- 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 +/- 5.1 vs. 3.6 +/- 3.0 cm2, p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 +/- 3.4 to 7.1 +/- 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 +/- 113 to 894 +/- 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 +/- 17 to 80 +/- 28 ms and from 12 +/- 7 to 18 +/- 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 +/- 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade. CONCLUSIONS: Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.     

Cardiac autonomic neuropathy and QT interval length. A follow-up study in diabetic patients

For evaluating the clinical significance of QT interval prolongation in diabetics with cardiac autonomic neuropathy (CAN), 53 diabetic patients were followed-up for 5 years or to death and the results of cardiovascular function tests as well as the values of QT intervals were repeatedly determined. At baseline investigation, the QTc intervals were significantly longer in diabetics with definitive (456 +/- 5 ms, mean +/- SEM, n = 17) than those with early (435 +/- 5 ms, n = 13, p less than 0.01) and without (413 +/- 4 ms, n = 23, p less than 0.001) signs of CAN or in controls (414 +/- 5 ms, n = 15, p less than 0.001). Thirteen patients died during the follow-up period (1 without, 2 with early and 10 with definitive signs of CAN) but QTc intervals did not differ significantly between patients with cardiac (456 +/- 9 ms, n = 8) and non-cardiac (459 +/- 15 ms, n = 5) causes of death. At reinvestigation of 40 patients, the severity of CAN worsened in 22 patients, remained unchanged in 15 patients and improved in 3 patients. Accordingly, the mean values of autonomic function tests decreased (beat-to-beat variation from 15 +/- 2 to 9 +/- 1 beats/min, p less than 0.01; 30:15 ratio from 1.19 +/- 0.03 to 1.09 +/- 0.02, p less than 0.01) while QTc interval increased (from 424 +/- 3 to 431 +/- 4 ms, p less than 0.01). It was concluded that CAN carries a poor prognosis in diabetic patients. Nevertheless, QTc interval prolongation could be evaluated as rather an additional sign of CAN than the only explanation for mechanism in the pathogenesis of sudden cardiac death in diabetic patients.     

Relationship between autonomic function, 24-h blood pressure, and albuminuria in normotensive, normoalbuminuric patients with Type 1 diabetes

We performed a battery of cardiovascular reflex tests, 24-h ambulatory blood pressure (AMBP) and 24-h urinary albumin excretion (UAE) in 116 normoalbuminuric and normotensive patients with Type 1 diabetes. Tests of heart rate variation (HRV) included the coefficient of variation (CV) and the low-frequency (LF), mid-frequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (CV, mean circular resultant — MCR), Valsalva ratio, and maximum/minimum 30:15 ratio. Autonomic neuropathy, characterized as an abnormality of more than two tests, was found in 33 patients. Patients with neuropathy compared to those without neuropathy showed significantly higher mean day and night diastolic blood pressure (dBP), mean systolic night blood pressure (sBP), and mean day and night heart rate (HR). Mean night dBP was inversely related to MF, HF, and HRV during deep breathing; mean day dBP and mean night sBP to HF; mean night HR to CV at rest, MF, HF, HRV during deep breathing, 30:15 ratio; mean day HR to HF, HRV during deep breathing, Valsalva, and 30:15 ratio. Mean 24-h UAE was not significantly different in neuropathic than in nonneuropathic patients. UAE was inversely related to CV at rest and HF. In the stepwise multiple regression analysis, reduced MF, HF, HRV during deep breathing, and high levels of UAE and HbA1c were associated with high night dBP. Autonomic neuropathy is already present in normotensive Type 1 diabetic patients at the normoalbuminuric stage and related to BP and albuminuria.     

Coronary calcification in long-term type 1 diabetic patients -- a study with multi slice spiral computed tomography.

The risk for cardiovascular disease in diabetes is excessive. Multislice spiral computed tomography (MSCT) is a new technique for the assessment of coronary calcification in coronary artery disease. The aim of the study was to evaluate the presence of coronary calcium in asymptomatic long-term type 1 diabetic patients. Seventy-one type 1 diabetic patients (age 48 +/- 9 y, HbA1c 7.7 +/- 1.2, BMI 24.4 +/- 2.8, duration of diabetes 26 +/- 9 y) without clinical evidence for coronary artery disease were assessed with MSCT. A volumetric score was used to calculate the coronary calcification (CC) score. Five cardiac reflex tests were performed to study patients for cardiac autonomic neuropathy. Coronary calcifications were detectable in 22 (31 %) type 1 diabetic patients (CC-score > 0, mean CC-score 174 +/- 228 [X+/-SD]). Fourty-nine (69 %) type 1 diabetic patients demonstrated no coronary calcifications (CC-score= 0). In patients with coronary calcifications, both cardiac autonomic neuropathy and retinopathy were detected more frequently than in those without (64 % vs. 29 %, p < 0.02; 59 % vs. 31 %; p < 0.02). Duration of diabetes was longer in patients with than without coronary calcification (32 +/- 10 y vs. 24 +/- 8 y, p < 0.01). Age, BMI, and HbA1c were not significantly different between patients with and without coronary calcification. The study demonstrates that nearly one third of asymptomatic long-term type 1 diabetic patients present with coronary calcifications. In the patients, there is evidence for an association between coronary calcification and both cardiac autonomic neuropathy and retinopathy. MSCT is a promising non-invasive approach to analyze early alterations of the coronary system in diabetic patients.     

Radionuclide assessment of left ventricular diastolic filling in diabetes mellitus with and without cardiac autonomic neuropathy

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.     

Comparison of various methods of assessment of heart rate variability including simple cardiovascular reflex tests as predictors of sudden cardiac death after myocardial infarction.

Long term heart rate variability is used for prediction of sudden cardiac death (SD). There are simpler methods of assessment of autonomic cardiac control - registration of heart rate response to reflex tests and determination of heart rate variability (HRV) on short ECG recordins. Comparative value for prognosis of SD after myocardial infarction (MI) of these 3 techniques has not been studied yet. METHODS: Valsalva maneuver with calculation of Valsalva ratio (VR) and deep breath test with calculation of difference between average maximal and minimal HR during first minute of test (HR difference - HRD) were performed in 188 patients on days 4-11 of MI (68.1% men, age 34-75 years, 93.6% on beta-blockers, without heart failure NYHA IV on the day of tests). Time and frequency domain HRV measures were assessed during 15 min at bed rest and at Holter monitoring for median 24 h on the same day as reflex tests. RESULTS: During follow up for 2.1+/-0.8 years there were 9 sudden and 13 non-sudden cardiac deaths. ROC analysis was used to determine cut-off values of VR, HRD and HRV measures for dichotomization of patients into those with low- and high-risk of SD and these values were used in logistic regression analysis. The following parameters were univariate predictors of SD: obtained at reflex tests - VR <1.13 (OR 7.8, 95% CI 1.6-39.0; p=0.012), HRD <3.36 (OR 4.3, 95% CI 1.1-16.9; p=0.034); HRV parameters from 15 min ECG recordings - total frequency power <739 ms(2), VLF power <294 ms(2), LF power <197 ms(2) and LF/HF <1.5; HRV parameters from long term ECG recording - LF power <491 ms(2), LF/HF <1.4. At multivariate analysis only LF power for 15 min <197 ms(2) among HRV parameters remained independent predictor of SD (OR 24.2, 95% CI 2.4-245.5; p=0.007). Other predictors were clinical - VF during acute phase of MI (OR 94.7, 95% CI 4.2-2115.2; p=0.004) and history of MI (OR 8.4, 95% CI 1.4-48.5; p=0.017). CONCLUSION: In this population of patients without severe heart failure low LF power on 15 min resting ECG recordings on days 4-11 of MI was more powerful predictor of sudden cardiac death during subsequent 2 years than other HRV parameters including heart rate response to Valsalva maneuver and deep breath test.     

Effects of combination antihypertensive therapy on baroreflex sensitivity and heart rate variability in systemic hypertension

Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to < 140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/- 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP control with modem antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.     

Continuous positive airway pressure therapy improves cardiovascular autonomic function for persons with sleep-disordered breathing

BACKGROUND: Sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular morbidity. Dysfunction of the cardiovascular autonomic nervous system may be a potential mechanism whereby SDB is linked to cardiovascular disease. Repetitive sympathetic activation during apneic episodes may impair cardiovascular reflex function, and increased sympathetic activity can stimulate renin release. Given that patients with SDB may have reduced cardiovascular autonomic function, the purpose of this study was to determine whether treatment with continuous positive airway pressure (CPAP) for 6 weeks would improve autonomic function. METHODS: Twenty-nine participants with a diagnosis of SDB, who completed 6 weeks of CPAP therapy, were evaluated for cardiovascular autonomic nerve fiber function at baseline and post therapy. Autonomic function tests included the following: R-R interval variation during deep breathing measured by vector analysis (ie, mean circular resultant [MCR]) and expiration/inspiration (E/I) ratio; and the Valsalva maneuver. Participants were also evaluated prior to CPAP therapy for plasma renin activity levels. RESULTS: Participants in this study showed improved cardiovascular autonomic function after 6 weeks of treatment (baseline vs follow-up) as assessed by the mean (+/- SD) MCR (33.2 +/- 22.5 vs 36.9 +/- 24.2, respectively; p < 0.05) and E/I ratio (1.20 +/- 0.12 vs 1.24 +/- 0.14, respectively; p < 0.01). Improved vagal tone was also noted for subjects with elevated renin levels. CONCLUSIONS: Treatment of SDB with CPAP for 6 weeks improved vagal tone and may be beneficial in reducing the risk of developing clinical manifestations of cardiovascular autonomic dysfunction (eg, increased risk of mortality).     

Heart rate variability in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure.

The prognosis of patients with heart disease and prediction of sudden cardiac death can be assessed through heart rate variability, an indirect measure of abnormal autonomic control. The authors have evaluated the heart rate variability by 24-hour ambulatory electrocardiographic monitoring in 25 diabetic patients, 19 ischemic heart disease patients, 18 congestive heart failure patients, and 10 normal subjects. Thirteen diabetic patients had autonomic neuropathy and 12 patients did not. Heart rate variability index (mean SD) in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure was significantly lower (34.5 +/- 12.6 ms, 43.7 +/- 15.4 ms, and 34.6 +/- 15.8 ms vs 65.6 +/- 16.7 ms, p less than 0.05) than that of normal subjects. Mean SD was significantly lower in patients with autonomic neuropathy as compared to patients without autonomic neuropathy (26.4 +/- 6.5 ms vs 44.2 +/- 11.0 ms, p less than 0.05) mean SD as compared to survivors: 49 +/- 7 ms in patients with mild ischemic heart disease, 48 +/- 15 ms in patients with severe ischemic heart disease, and 23 +/- 7 ms in patients who died. Similarly, the mean SD in 4 congestive heart failure patients who died was lower significantly (p less than 0.05) than in those who survived (19.0 +/- 5.6 ms vs 40.0 +/- 14.5 ms). Among congestive heart failure patients, clinical improvement by therapy was associated with a significant increase in mean SD. When the mean SD of 30 ms was used as the cutoff point for detection of autonomic dysfunction or patient death, specificity exceeded 90% and sensitivity was 75%.(ABSTRACT TRUNCATED AT 250 WORDS)     

High prevalence and severity of cardiac autonomic neuropathy in Vietnamese diabetic patients.

AIMS: Malnutrition is frequent in Vietnamese people and may influence cardiac autonomic neuropathy (CAN). The aim of the present study was to investigate cardiac autonomic function in healthy subjects living in Vietnam and the prevalence of CAN in Vietnamese diabetic patients. METHODS: One hundred and five diabetic patients (BMI = 19.8 +/- 0.3 kg/m(2)), 50 Type 1 and 55 Type 2, living in Hué (Vietnam) were selected and compared with 60 non-diabetic healthy Vietnamese controls (BMI = 20.8 +/- 0.2 kg/m(2)) and also European controls. CAN function was evaluated by five standardized tests: three tests for heart rate variations (HRV) which depend mainly on parasympathetic activity, and two tests for blood pressure (BP) response which depend mainly on sympathetic activity. RESULTS: With age taken into account, 41 of the 60 Vietnamese controls had at least mild CAN, as defined by one abnormal test for HRV when compared with the European control series, and 11 of them had two or three abnormal tests. Among the Vietnamese control men, those with abnormal HRV had lower BMI than those without (P = 0.036). Seven Vietnamese controls had postural hypotension and 16 had an abnormal BP response to the handgrip test. Compared with the Vietnamese controls, 71 diabetic patients (67.6%), 40 Type 1 and 31 Type 2, had at least mild CAN, 37 of them had two or three abnormal HRV tests, and 56 diabetic patients (53.3%) had an abnormal BP response to the sympathetic tests. Abnormal HRV were associated with significantly lower BMI, waist and hip circumferences, longer diabetes duration and higher fasting blood glucose. In the logistic regression analyses, abnormal HRV were associated significantly with duration of diabetes and BMI in patients with Type 2 diabetes. CONCLUSIONS: Cardiac autonomic dysfunction is frequent in normal Vietnamese subjects. CAN appears to be a more frequent complication of diabetes in Vietnam than in Western countries and diabetic parasympathetic dysfunction is frequently associated with sympathetic disorders. This confirms the deleterious effect a poor nutritional state has on cardiac autonomic function.     

Evidence of early impairment of parasympathetic reflexes in insulin dependent diabetics without autonomic symptoms

Cardiovascular (CV) autonomic functions were assessed in 50 insulin-dependent diabetic patients and in 30 controls using a battery of autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (LS), Sustained Handgrip (SHG) and Postural Hypotension (PH). The results were compared with those obtained from a study of cardiac resting adjustment to different static postures (quiet lying and standing). 10 diabetics with abnormal responses to the majority of tests were considered affected by Diabetic Autonomic Neuropathy (DAN); 15 with some abnormal of borderline responses were defined much less than Borderlines much greater than. The remaining 25 diabetics, while displaying lower values than the controls in parasympathetic tests, had much less than normal much greater than autonomic responses. The VR mean (+/- SD) value was 1.71 +/- 31 in much less than normal much greater than diabetics and 2.01 +/- 0.29 in controls (p less than 0.001); the DB mean value was 20.6 +/- 87 and 28 +/- 8.13 (p less than 0.001), and the LS mean value 1.16 +/- 0.12 and 1.33 +/- 0.18 (p less than 0.001) respectively. No significant differences were found in the sympathetic tests (SHG, PH). However Heart Rate (HR) adjustment of diabetics with normal CV responses to immobile standing (RR mean 783 +/- 136 ms) and lying (RR mean increment of 25 +/- 11%; p less than 0.001) was similar to that of controls who had a resting HR standing (RR mean 749 +/- 104 ms) and lying (RR mean 884 +/- 116 ms) with a mean increment of 20.2 +/- 10.9% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac autonomic tone and its relation to nonsustained ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy

BACKGROUND: In contrast to postinfarct patients, little is known about cardiac autonomic tone and its relation to spontaneous ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy (IDC). Both heart rate variability (HRV) and baroreflex sensitivity (BRS) are indices of autonomic innervation of the heart. HYPOTHESIS: The aim of the present study was to determine the relation between cardiac autonomic tone assessed by HRV and BRS and spontaneous nonsustained ventricular tachycardia (NSVT) on Holter in a large patient population with IDC. METHODS: 24-h digital Holter recordings including HRV analysis and BRS testing were prospectively performed in 137 patients with IDC and preserved sinus rhythm. Mean age was 48 +/- 12 years, and mean left ventricular (LV) ejection fraction was 32 +/- 9%. The HRV analysis on Holter included the mean RR interval (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing more than 50 ms (pNN50). Testing for BRS was performed noninvasively using the phenylephrine method. RESULTS: Of 137 study patients, 42 (31%) had spontaneous NSVT on 24-h Holter. Compared with patients without NSVT, patients with NSVT on Holter had a higher New York Heart Association (NYHA) functional class (NYHA III: 40 vs. 18%, p < 0.01), a lower ejection fraction (29 +/- 9 vs. 34 +/- 9%, p = 0.01), and an increased LV end-diastolic diameter (69 +/- 8 mm vs. 66 +/- 7 mm, p = 0.03). The HRV variables rMSSD, pNN50, RRm, and BRS did not differ significantly between patients with and without spontaneous NSVT. Only SDNN on Holter was slightly lower in patients with versus without NSVT (106 +/- 45 vs. 121 +/- 46 ms, p = 0.08). CONCLUSIONS: Patients with IDC and spontaneous NSVT on Holter are characterized by a higher NYHA functional class, a lower LV ejection fraction, an increased LV end-diastolic diameter, and a tendency toward a lower SDNN value compared with patients without NSVT. The remaining measures of HRV including rMSSD and pNN50 reflecting primarily tonic vagal activity, as well as BRS reflecting predominantly reflex vagal activity, were similar in patients with and without NSVT. The prognostic significance of these findings in patients with IDC is currently under investigation in the Marburg Cardiomyopathy Study (MACAS) at our institution.     

The prognostic value of troponin T and echocardiography in acute pulmonary edema

OBJECTIVE: Several studies documented the relevance of autonomic activity in the pathophysiology of heart failure. In our study we evaluated the adjustment of this activity under different stimuli, by means of heart rate variability (HRV), and correlated these findings with long-term mortality and sustained VT occurrence. PATIENTS AND METHOD: Fifty-three patients (mean age 54+/-9 years) with heart failure were submitted to time and frequency domain HRV analysis. This latter analysis was performed at rest, during paced breathing and during passive tilt. RESULTS: Lower standard deviation of RR intervals (76.76+/-24 versus 107.70+/-43, p=0.02), mean of the 5-min standard deviations of RR intervals (35.14+/-15 versus 62.39, p<0.01), standard deviation of the 5-min average RR intervals (69.42+/-19 versus 91.79+/-30, p=0.02), and baseline Low-Frequency (LF) power (15.15+/-12 versus 40.39+/-24 nu, p=0.001) characterized patients who died. Paced breathing induced a significant reduction of LF (40.39+/-24 to 20.12+/-18 nu, p<0.0001) and increase of High Frequency power (HF) (47.31+/-23 to 70.63+/-16 nu, p<0.0001) in survivors, while tilting induced a reduction of HF (47.31+/-23 to 29.80+/-16 nu, p<0.0001). Patients who died did not show significant variation of HRV neither during paced breathing nor during tilt. Reduced time domain indexes were significantly correlated to sustained VT occurrence. CONCLUSIONS: Patients with heart failure with a better prognosis are characterized by a responsiveness of autonomic modulation. Simple maneuvers, such as tilting and paced breathing, seem to provide more useful information, than the baseline evaluation of autonomic status, in identifying patients with a higher mortality. Time domain analysis was more helpful to estimate arrhythmic risk.     

Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure.

OBJECTIVES: This study sought to report long-term changes of cardiac autonomic control by continuous, device-based monitoring of the standard deviation of the averages of intrinsic intervals in the 288 five-min segments of a day (SDANN) and of heart rate (HR) profile in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT). BACKGROUND: Data on long-term changes of time-domain parameters of heart rate variability (HRV) and of HR in highly symptomatic HF patients treated with CRT are lacking. METHODS: Stored data were retrieved for 113 HF patients (New York Heart Association functional class III to IV, left ventricular ejection fraction < or =35%, QRS >120 ms) receiving a CRT device capable of continuous assessment of HRV and HR profile. RESULTS: The CRT induced a reduction of minimum HR (from 63 +/- 9 beats/min to 58 +/- 7 beats/min, p < 0.001) and mean HR (from 76 +/- 10 beats/min to 72 +/- 8 beats/min, p < 0.01) and an increase of SDANN (from 69 +/- 23 ms to 93 +/- 27 ms, p < 0.001) at three-month follow-up, which were consistent with improvement of functional capacity and structural changes. Different kinetics were observed among these parameters. The SDANN reached the plateau before minimum HR, and mean HR was the slowest parameter to change. Suboptimal left ventricular lead position was associated with no significant functional and structural improvement as well as no change or even worsening of HRV. The two-year event-free survival rate was significantly lower (62% vs. 94%, p < 0.005) in patients without any SDANN change (Delta change < or =0%) compared with patients who showed an increase in SDANN (Delta change >0%) four weeks after CRT initiation. CONCLUSIONS: Cardiac resynchronization therapy is able to significantly modify the sympathetic-parasympathetic interaction to the heart, as defined by HR profile and HRV. Lack of HRV improvement four weeks after CRT identifies patients at higher risk for major cardiovascular events.     

QT dispersion in insulin-dependent diabetics]

BACKGROUND: The measurement of the dispersion of the QT interval reflects regional repolarization differences in the heart which in turn can elicit the onset of arrhythmias by means of re-entry mechanism. Therefore, inter-lead QT dispersion has been proposed as novel indicator of arrhythmogenic risk that can predict severe ventricular arrhythmias or sudden death. The present study was conducted to evaluate QT dispersion in diabetic insulin-dependent patients with autonomic neuropathy. METHODS: We recruited three groups of 10 patients with the same age, sex, body weight distribution: 1) group DAN+ (diabetics with neuropathy); 2) group DAN- (diabetics without neuropathy); and 3) group CTRL (healthy control group). The patients underwent two-dimensional color-Doppler echocardiography and 12-lead electrocardiogram, 25 and 50 mm/s paper speed (gain 10 mm/mU). The QTc dispersion was determined as the difference between the maximum and the minimum value of the QTc interval in different leads of the ECG recording. QT interval was corrected (QTc) by heart rate according to the Bazett's formula. Cardiovascular autonomic function was evaluated by Ewing's tests (heart rate and blood pressure measurement during lying to standing, deep breathing, hand-grip isometric stress test and Valsalva's maneuver). RESULTS: QT dispersion was significantly greater (p < 0.01) in the patients with autonomic neuropathy (51 +/- 10 ms) than in the patients without autonomic neuropathy (29 +/- 6 ms) or in healthy control subjects (26 +/- 5 ms). CONCLUSIONS: Our data suggest that diabetic neuropathy, associated with an increased QT dispersion, shows a higher risk for serious ventricular arrhythmias and sudden cardiac death.     

Role of heart rate variability in the early diagnosis of diabetic autonomic neuropathy in children

BACKGROUND: Diabetic autonomic neuropathy (DAN) is a major complication of diabetes. DAN has been shown to be closely related to glycemic control. To contribute significantly to the morbidity and mortality of the disease, and to be indicative of an increased risk of cardiovascular events. Tests assessing the function of the autonomic nervous system, such as the response of heart rate and blood pressure to maneuvers stimulating the autonomic nervous system, including deep breathing. Valsalva maneuver and standing, allowed to detect signs of DAN in adolescents; however, the sensitivity of such tests in revealing an early impairment of the autonomic nervous system proved low. Several studies found heart rate variability (HRV) to be useful in assessing the dysfunction of the autonomic nervous system in diabetic children and adolescents, but only few HRV parameters were evaluated in most of them. OBJECTIVE: To study cardiac autonomic nervous system in diabetic children, and to investigate whether the duration of diabetes and the degree of metabolic control are determinants for the development of DAN in children. PATIENTS AND METHODS: We analyzed HRV in 50 asymptomatic patients with insulin-dependent diabetes mellitus (IDDM) and 30 healthy children matched for age and sex. RESULTS: Patients with a history of diabetes > 8 years showed significant alterations of the autonomic nervous system (significant reduction of r-MSSD, pNN50, HF and increase in LF/HF). Conversely, only a reduction in pNN50 was found in patients with a disease duration < 8 years. Furthermore, we also observed significant HRV abnormalities in patients with an impaired metabolic control of diabetes. Compared to controls, patients with glycosylated hemoglobin blood levels (HbA(1C)) > 8% showed a significant reduction of r-MSSD, pHH50 and total power spectrum, whereas no HRV abnormalities were detected in patients with an HbA(1C) < 8%. CONCLUSIONS: HRV analysis can detect early subclinical alterations of the autonomic nervous system in asymptomatic patients with IDDM, which seem to consist mainly in a parasympathetic impairment. Autonomic dysfunction is associated both with the duration and an inadequate metabolic control of the disease.     

Incipient cardiovascular autonomic imbalance revealed by wavelet analysis of heart rate variability in Type 2 diabetic patients.

AIM: Incipient cardiovascular autonomic imbalance is not readily diagnosed by conventional methods. Spectral analysis of heart rate variability (HRV) by wavelet transform (WT) was used to measure cardiovascular autonomic function in patients with Type 2 diabetes. METHODS: Thirty-two diabetic patients without (D), 26 with cardiovascular autonomic neuropathy (DAN) and 72 control subjects (C) participated. A 30-min HRV time series was analysed by wavelet transformation and four characteristic frequency intervals were defined: I (0.0095-0.021 Hz), II (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz). RESULTS: When compared with C, in both D and DAN the normalized power and amplitude of interval II were increased and of interval IV decreased, resulting in a significantly higher II/IV ratio. Furthermore, in DAN the normalized power and amplitude of interval I were increased and of interval III decreased when compared with the D and C groups. The diabetic patients were divided in two equal subgroups according to HbA(1c) < 8.0% and >or= 8.0%. In the subgroup with HbA(1c) >or= 8.0%, normalized power in interval II was significantly higher and in interval IV significantly lower than in the subgroup with HbA(1c) < 8.0%. In D, but not in DAN patients prescribed ACE inhibitors, the absolute amplitude and power of oscillations were significantly higher than in patients not taking ACE inhibitor therapy. CONCLUSIONS: Patients with diabetes have increased sympathetic and decreased parasympathetic cardiac activity regardless of the presence of autonomic neuropathy. Glycaemic control and treatment with ACE inhibitors may favourably influence HRV in diabetic patients without autonomic neuropathy.     

The effect of glucose-insulin-potassium solution on ventricular late potentials and heart rate variability in acute myocardial infarction.

BACKGROUND: Blunted heart rate variability (HRV) and presence of ventricular late potentials (VLPs) are known to correlate with an increased risk of ventricular tachycardia and sudden cardiac death in acute myocardial infarction (AMI). In the present study, we investigated the effect of glucose-insulin-potassium (GIK) solution on the VLPs and HRV in AMI. METHODS: Seventy-two consecutive patients with first Q wave AMI were randomized to GIK solution and placebo. HRV analysis and ambulatory electrocardiographic recordings were taken in all patients between 24 and 48 h. Sub-maximal exercise testing and echocardiography were performed and signal-averaged electrocardiography (SAECG) was recorded before discharge. RESULTS: Total filtered QRS duration (FQRS: 102 +/- 7 versus 108 +/- 11 ms; P < 0.05), low-amplitude signal (LAS: 25 +/- 8 versus 32 +/- 11 ms; P < 0.01) and frequency of VLPs (21 versus 45%; P < 0.05) were found to be significantly lower while root-mean-square voltage of the terminal 40 ms of QRS (RMS-40: 45 +/- 18 versus 36 +/- 20 microV; P < 0.05), and left ventricular ejection fraction (EF: 55 +/- 6 versus 48 +/- 7; P < 0.05) were significantly higher in the GIK group when compared to placebo. During the hospital period, the presence and frequency of post-myocardial infarction angina were significantly lower in the GIK group (15 versus 29%, P < 0.05), whereas an insignificant decrease in frequency of ventricular arrhythmias was observed in these patients. On HRV analysis, there was no significant difference between two groups in either time domain (SD, SDNN, RMS-SD) or frequency domain (HF, LF, LF/HF ratio) parameters. CONCLUSION: GIK solution may be beneficial to VLPs, ischaemic events, and left ventricular systolic performance in the early period of AMI. This therapy has no significant effect on HRV in AMI patients.