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Background: Children with transposition of the great arteries, in whom an arterial switch operation (ASO) is performed, have been shown to have an increased incidence of sudden death, which may be due to cardiac autonomic imbalance and repolarisation instability. We hypothesised that i) cardiac norepinephrine (NE) kinetics and ii) arterial baroreflex sensitivity (BRS), reflecting sympathetic activity and vagal function respectively, are altered in this group., Methods and Results: 17 children (15.8 ± 1.5 years of age) with ASO-surgery in the neonatal period were studied. 17 had cardiac BRS assessed by spontaneous fluctuations of systolic blood pressure and RR-interval, and repolarisation was measured as QT variability index. Matched healthy subjects were controls. Cardiac vagal function and repolarisation pattern were unchanged following ASO-surgery. At cardiac catheterisation, we infused tritiated NE in 8 of these children to examine total body and cardiac sympathetic function at baseline and following 5 min of adenosine infusion to induce reflex sympathetic activation. Blood was sampled simultaneously from the aorta and coronary sinus. Cardiac fractional extraction of ([3H])NE was substantially lower in operated children, being 56 ± 10 vs. 82 ± 9% (p=0.0001). Following i.v. adenosine in the operated group, NE total body spillover doubled vs. baseline (p<0.002) and the coronary venous-arterial concentration gradient of ([3H])dihydroxyphenylglycol increased 4-fold (p=0.04)., Conclusions: Arterial switch operation performed neonatally appears to leave cardiac vagal function intact and, although cardiac sympathetic activation in response to adenosine occurs, cardiac neuronal NE reuptake is impaired. This may be pro-arrhythmic by reducing removal capacity of NE from the cardiac synaptic cleft., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective:   Obese children present with various cardiovascular risk factors affecting their future health. In adults, cardiac autonomic function is a major risk factor, predicting cardiovascular morbidity and mortality. We hypothesized that obese children and adolescents had a lower cardiac vagal activity than lean subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS), reflecting the dynamic regulation of cardiac vagal function, in large groups of obese and lean young individuals., Methods and Results:   Cardiac BRS, using the sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls) and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared to both overweight and lean subjects [16±7 versus 21±9 (P<0·01) and 22±10 ms per mmHg (P<0·0001), respectively]. The differences remained after correcting for age, gender and pubertal status., Conclusion:   Children with obesity had low vagal activity at rest, and there was no gender difference., (© 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objectives: Patients treated for major depressive disorder are at increased risk for sudden cardiac death. Impaired arterial baroreflex function has been associated with ventricular arrhythmias. Our hypothesis was that arterial baroreflex dysfunction prevails in major depressive disorder and that electroconvulsive therapy in conjunction to medical therapy would improve both depressive symptoms and baroreflex function., Methods: Thirty-three patients with major depressive disorder who were treated in hospital were studied before and after electroconvulsive treatment. Eighteen patients underwent follow-up investigations 6 months after discharge. ECG and beat-to-beat blood pressures were recorded continuously. Arterial baroreflex sensitivity (BRS) and effectiveness index were calculated. Twenty healthy subjects were examined for comparison., Results: Heart rate and systolic blood pressures were elevated (P < 0.01 for all) in depressive patients before treatment when compared with healthy subjects, whereas arterial BRS and baroreflex effectiveness were reduced (10 +/- 7 vs. 15 +/- 5 ms/mmHg and 0.35 +/- 0.20 vs. 0.48 +/- 0.14, P < 0.01 for both). Whereas depressive symptoms decreased after treatment (P < 0.05), blood pressures, heart rate, arterial BRS, and effectiveness remained unchanged. At follow-up, 6 months after discharge all variables were unchanged when compared with values obtained at discharge., Conclusion: Both the sensitivity and the number of times the arterial baroreflex is being active are reduced in major depressive disorder and this baroreflex dysfunction may prevail long-term when depressive symptoms have improved.

Background: The "nondipping" pattern (NDP) of blood pressure, characterized by the absence of the reduction in blood pressure (BP) that typically takes place during the night time, has been associated with elevated cardiovascular morbidity, including stroke, myocardial infarction, and sudden cardiac-related death. In various cardiovascular diseases, reduced vagal control of cardiac function and elevated lability of cardiac repolarization have been associated with increased risk for ventricular arrhythmia and sudden death. The aim of this study was to assess temporal QT variability, arterial baroreflex sensitivity (BRS), and baroreflex effectiveness index (BEI) in two groups of otherwise healthy subjects, one group consisting of those with a normal BP pattern and the other with a nondipping BP pattern., Methods: Ninety-five healthy subjects underwent 24-h ambulatory BP (AMBP) monitoring. A minimum of 10% reduction in BP during the night relative to daytime levels is considered normal (as found in "dippers"). These individuals were classified as "dippers" (n = 59) and individuals without 10% reduction in BP during night were classified as "nondippers" (n = 36). Electrocardiogram (ECG) readings and beat-to-beat BP were recorded at 1,000 Hz with the subjects at rest in the supine posture for 20 min. BRS, BEI, and QT variability index (QTVI) were calculated., Results: There were no differences between the study groups with respect to age, gender, and average BP. Nondippers showed an increase in QTVI (-1.28 +/- 0.48 in nondippers vs. -1.52 +/- 0.29 in dippers, P < 0.05) and a decrease in BEI (0.34 +/- 0.17 in nondippers vs. 0.43 +/- 0.17 in dippers, P < 0.05), whereas BRS did not differ between the groups., Conclusion: A nondipping BP pattern in healthy subjects is associated with elevated myocardial repolarization lability and impaired baroreflex function, suggesting dysfunction of the autonomic nervous system.

Objectives: Impaired arterial baroreflex sensitivity (BRS) has been associated with cardiac mortality and non-fatal cardiac arrests after a myocardial infarction. Patients with chronic renal failure (CRF) have a poor prognosis because of cardiovascular diseases, and sudden death is common. The aim of this study was to assess whether BRS or the baroreflex effectiveness index (BEI), a novel index reflecting the number of times the baroreflex is active in controlling the heart rate in response to blood pressure fluctuations, is associated with prognosis in CRF., Methods: Hypertensive patients with CRF who were treated conservatively, by haemodialysis or peritoneal dialysis were studied. Electrocardiogram and beat-to-beat blood pressures were recorded continuously and BRS and BEI were calculated. Patients were then followed prospectively for 41 +/- 15 months (range 1-64)., Results: During follow-up 69 patients died. Cardiovascular diseases and uraemia accounted for the majority of deaths (60 and 20%, respectively), whereas sudden death occurred in 15 patients. In adjunct with established risk factors such as age, diabetes, congestive heart failure and diastolic blood pressure, reduced BEI was an independent predictor of all-cause mortality among CRF patients [relative risk (RR) 0.50, 95% confidence interval (CI) 0.33-0.71 for an increase of one standard deviation in BEI, P < 0.001]. Diabetes and reduced BRS were independent predictors of sudden death (RR 0.29, 95% CI 0.09-0.86 for an increase of one standard deviation in BRS, P=0.022)., Conclusions: Both BEI and BRS convey prognostic information that may have clinical implications for patients with cardiovascular diseases in general.

Background: Recent guidelines for the management of arterial hypertension have proposed that, to prevent cardiovascular disease, lifestyle modifications are required even in the case of high-normal blood pressure (HNBP)., Objective: To assess myocardial repolarization and spontaneous cardiac baroreflex sensitivity (BRS) in newly diagnosed and never-treated individuals., Design and Participants: We studied healthy individuals with HNBP according to the 2003 European Society of Hypertension-ESC guidelines and, for comparison, patients with renovascular hypertension (RVH) and healthy individuals with normal blood pressure (NBP)., Main Outcome Measures: Electrocardiogram and beat-to-beat blood pressure were recorded and spontaneous cardiac baroreflex sensitivity and the temporal QT interval variability index (QTVI) were calculated., Results: Individuals with HNBP had increased QTVI values compared with those with NBP (-1.23 +/- 0.37 compared with -1.52 +/- 0.26; P < 0.05), whereas patients with RVH had additionally increased QTVI values that were greater than those in healthy individuals with NBP or HNBP (-0.81 +/- 0.75; P < 0.05 compared with both groups). BRS was reduced in both groups of individuals with increased blood pressures compared with NBP (8.2 +/- 4.1 ms/mmHg for individuals with HNBP, 6.1 +/- 4.3 ms/mmHg for patients with RVH and 10.8 +/- 3.5 ms/mmHg for NBP; P < 0.05 for both)., Conclusion: In otherwise healthy individuals, even a moderate blood pressure increase is associated with increased myocardial repolarization lability and reduced baroreflex sensitivity (BRS). Patients with RVH have an additionally increased QTVI, with values similar to those reported in congestive heart failure. Future studies are needed to establish the value of QTVI and BRS measurements among individuals with HNBP in predicting the risk of progression to hypertension and end-organ damage.

Background: Impaired arterial baroreflex function has been associated with an increased risk of ventricular arrhythmia and sudden death. This has also been suggested for patients with chronic renal failure (CRF) who are at high risk for cardiovascular morbidity. The aim of this study was to investigate the arterial baroreflex function in CRF patients with emphasis on analyzing the time during which the arterial baroreflex is active, the baroreflex effectiveness index (BEI)., Methods: Beat-to-beat blood pressure (measured with Portapres) and electrocardiography were continuously registered during 30 min rest in 216 hypertensive CRF patients on hemodialysis (n=95), continuous ambulatory peritoneal dialysis (n=59), or conservative treatment (n=59). The spontaneous sequence method was used to calculate BRS and BEI. Age-matched healthy subjects (n=43) were examined for comparison., Results: The BRS was reduced by 51% and the BEI by 49% in CRF patients compared with healthy subjects (P<.001 for both). In addition, CRF patients with diabetes showed further reductions compared with patients without diabetes (15% reduction of BRS and 44% of BEI, P<.01 for both). The treatment modality for renal failure had no effect on BRS or BEI. In a multivariate linear regression analysis, age, body mass index, and systolic blood pressure were independent predictors of BRS, whereas age and diabetes were independent predictors of BEI in patients with CRF., Conclusions: We conclude that BEI, which is markedly reduced in hypertensive patients with CRF, may convey information on arterial baroreflex function that is complementary to BRS.

Spontaneous baroreflex sensitivity (BRS), the reflex heart rate modulation in response to blood pressure changes (predominantly an index of cardiac vagal activity) and temporal QT variability (an index of myocardial repolarization) have been demonstrated to convey important prognostic information. The information about reproducibility of BRS and temporal QT variability is limited and there is lack of information regarding patients with cardiovascular diseases. We investigated reproducibility of spontaneous BRS using the sequence technique and temporal QT variability index (QTVI) in terms of intra-, interexaminer and within-subject variability in end-stage renal disease patients (ESRD, n=17, age 55+/-14 years) and healthy subjects (HS, n=29, age 32+/-12 years, P<0.01). ECG and blood pressure (Portapres) were recorded on two separate days and BRS and QTVI were evaluated by two independent examiners. The mean heart rate was similar in ESRD patients in comparison to healthy controls, whereas the mean arterial pressure was 13 % higher in ESRD patients (P<0.01). Spontaneous BRS was 62% lower (P<0.01) and QTVI was 41% higher in ESRD patients (P<0.01) compared to healthy subjects, respectively. Coefficient of variation (CV) of within-subject reproducibility of BRS and QTVI measurements was moderate (BRS: 33 % for ESRD, 27% for HS; QTVI: 40% for ESRD, 18% for HS). The 95% limit of within-subject reproducibility of BRS measurements was 3.8 ms/mm Hg for ESRD patients and 8.1 ms/mm Hg for healthy subjects; whereas the 95% limit of reproducibility of within-subject reproducibility of QTVI measurements was 0.73 for ESRD patients and 0.55 for healthy subjects. Concordance correlation coefficients of within-subject variability of BRS and QTVI were between 0.74 and 0.83 in both groups. CV of intra- and inter-examiner reproducibility of BRS and QTVI measurements in both groups ranged between 1 and 11%. In conclusion, the intra- and inter-examiner reproducibility/agreement of BRS and QTVI were high, whereas the within-subject reproducibility of these two methods was moderate, in both ESRD patients and healthy subjects. Thus, small differences in BRS and QTVI in longitudinal/interventional studies should be interpreted with caution.

Objective: Sympathetic nerve activity is increased in hypertensive patients with renal artery stenosis. Less is known about cardiac vagal function in these patients before and after renal angioplasty. The aim of the present study was to investigate cardiac baroreceptor reflex sensitivity together with total body noradrenaline (NA) spillover in hypertensive patients with renal artery stenosis before, and in some patients, 1 year after renal angioplasty., Material and Methods: Spontaneous baroreceptor reflex sensitivity and total body noradrenaline (NA) spillover were measured in patients with renovascular hypertension before intervention (n = 18), patients being cured/improved 1 year after renal angioplasty (n = 5) and age-matched healthy subjects (n = 25)., Results: Hypertensive patients with renal artery stenosis had higher total body NA spillover (4630 +/- 619 versus 3132 +/- 210 pmol/min, P < 0.05) and reduced cardiac baroreceptor reflex sensitivity (6.1 +/- 1.0 versus 10.7 +/- 1.0 ms/mmHg, P < 0.01) compared with healthy subjects. Similar results were obtained (before intervention) in a subgroup of patients (n = 9) with renovascular hypertension defined as cured/improved 1 year following renal angioplasty. Baroreceptor reflex sensitivity improved after renal angioplasty in a subset of patients showing good blood pressure control 1 year after intervention (6.4 +/- 0.7 to 9.4 +/- 1.7 ms/mmHg, P < 0.05)., Conclusions: Patients with renovascular hypertension showed reduced cardiac baroreceptor reflex sensitivity and increased noradrenergic activity, which to some extent was reversed 1 year following successful renal angioplasty.

Abstract: Aims: To examine changes in renal sympathetic outflow in response to cardiac unloading with nitroglycerin (GTN) in patients with chronic heart failure (CHF) and healthy subjects (HS). Methods and Results: Renal (RNAsp) and total body (TBNAsp) noradrenaline (NA) spillover were measured with radiotracer methods in 16 patients with CHF (50±3 years, LVEF 20±1%) and nine HS (57±2 years) during right heart and renal vein catheterisation. Low dose GTN decreased mean pulmonary artery pressure (PAm: CHF −7±2 mm Hg, HS −4±1 mm Hg, p<0.05 vs. baseline) but not mean arterial pressure (MAP: CHF −2±1 mm Hg, HS −2±1 mm Hg) and did not affect RNAsp in any of the study groups. High dose GTN lowered MAP (CHF −12±1 mm Hg, HS −12±2 mm Hg, p<0.05 vs. baseline) and PAm (CHF −13±2 mm Hg, HS −5±1 mm Hg, p<0.05 vs. baseline) and was accompanied by a significant reduction in RNAsp only in CHF (1.3±0.1 nmol/min baseline to 0.9±0.2 nmol/min, p<0.05), whereas RNAsp in HS remained unchanged. Conclusions: In spite of a reduction in both arterial pressure and cardiac filling pressures, renal sympathetic activity decreased in CHF and did not increase in HS. These findings suggest that the altered loading conditions resulting from high-dose GTN infusion have renal sympathoinhibitory effects. [Copyright &y& Elsevier]