Cardiac Sympathetic Activity In Patients Research Articles

Remote ischemic peri-conditioning suppressed the activation of cardiac sympathetic nervous system in patients with acute myocardial infarction: a randomized controlled trial

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). Remote ischemic peri-conditioning (RIPC) is reported to improve clinical outcome in patients with AMI. However, there is not fully clarified whether RIPC could have an effect on cardiac sympathetic activity. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic activity in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent percutaneous coronary intervention to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80) upon arrival to the cardiac catheterization laboratory. After excluding inappropriate patients such as those who were diagnosed with other than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). The primary endpoint was cardiac sympathetic activity assessed by the cardiac MIBG imaging washout rate (WR) at discharge and 1 year after discharge. WR and late heart-to-mediastinum ratio (HMR) in cardiac MIBG was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. There was no significant difference in WR between two groups at discharge. Although WR was significantly decreased 1 year after the discharge in both groups, patients in RIPC group showed significantly lower WR than those in control group (22.0 [15.1-30.6]% and 26.5 [18.4-34.4]%, p=0.0269) 1 year after the discharge. Late HMR significantly decreased during 1-year follow-up in patients only in RIPC group (p=0.0133) and patients in RIPC group tended to show higher late HMR compared to those in control group (2.01 [1.79-2.25] and 1.92 [1.72-2.11], p=0.0581) 1 year after the discharge. Conclusion(s) Remote ischemic peri-conditioning could suppress the augmented cardiac sympathetic activity in patients with acute myocardial infarction during 1-year follow-up.

Cardiac Sympathetic Activity and Rhythm Control Following Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation-A Prospective 123I-mIBG-SPECT/CT Imaging Study.

Background: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. Results: PVI with point-by-point radiofrequency ablation led to a significantly (p < 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. Conclusions: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

Abdominal obesity, and not general obesity, is associated with a lower 123I MIBG heart-to-mediastinum ratio in heart failure patients with preserved ejection fraction.

The relationship between general obesity or abdominal obesity (abdominal circumference of ≥85cm in men and ≥ 90cm in women) and the heart-to-mediastinum ratio (HMR), a measure of cardiac sympathetic innervation, on cardiac iodine-123-metaiodobenzylguanidine scintigraphy (MIBG) in patients with heart failure with preserved ejection fraction (HFpEF) has not been clarified. A total of 239 HFpEF patients with both MIBG and abdominal circumference data were examined. We divided these patients into those with abdominal obesity and those without it. In the cardiac MIBG study, early phase image was acquired 15-20min after injection, and late phase image was acquired 3h after the early phase. A HMR obtained from a low-energy type collimator was converted to that obtained by a medium-energy type collimator. Early and late HMRs were significantly lower in those with abdominal obesity, although washout rates were not significantly different. The incidence of patients with early and late HMRs <2.2 was significantly higher in those with abdominal obesity. Multivariate linear regression analysis revealed that abdominal obesity was independently associated with early HMR (standardized β = -0.253, P = 0.003) and late HMR (standardized β = -0.222, P = 0.010). Multivariate logistic regression analysis revealed that abdominal obesity was independently associated with early (odds ratio [OR] [95% confidence interval {CI}] = 4.25 [2.13, 8.47], P < 0.001) and late HMR < 2.2 (OR [95% CI] = 2.06 [1.11, 3.83], P = 0.022). Elevated BMI was not significantly associated with low early and late HMR. The presence of abdominal obesity was significantly associated with low early and late HMR even in patients without elevated BMI values. Abdominal obesity, but not general obesity, in HFpEF patients was independently associated with low HMR, suggesting that visceral fat may contribute to decreased cardiac sympathetic activity in patients with HFpEF. UMIN000021831.

Night-Time Premature Ventricular Complex Positively Correlates With Cardiac Sympathetic Activity in Patients Undergoing Radiofrequency Catheter Ablation

Patients with premature ventricular complexes (PVCs) usually experience accompanying alterations of the autonomic nerve system. The timing of PVC occurrence is associated with different circadian rhythms, which may be related to the autonomic nerve imbalance. The relationship between night-time PVC and cardiac autonomic nervous activity is still obscure. Our study aimed to investigate the relationship between the number of night-time PVCs and cardiac autonomic nervous activity. We enrolled 72 patients with frequent PVCs and 27 without PVCs. The patients with PVCs were divided into two groups based on the number of night-time PVCs (i.e., PVCs occurring between 10 pm and 6 am/24-hr total PVCs; group 1: n=34, <30%; group 2: n=38, >30%). At baseline, 12-lead electrocardiogram and 24-hour Holter recording were performed. When the number of PVCs declined significantly after radiofrequency catheter ablation, Holter monitoring was performed again. Heart rate (HR) variability, mean 24-hour HR, mean daytime HR, and mean night-time HR were analysed. With a greater number of night-time PVCs, group 2 had a lower standard deviation of all NN intervals (SDNN; 116.5±38.3 vs 135.3±37.8 ms; p=0.035) and increased mean 24-hour HR (77.3±9.2 vs 73.4±7.5 beats per min; p=0.05) than group 1. The SDNN was negatively correlated with the number of night-time PVCs and mean night-time HR (r= -3.04 and r= -0.504, respectively; p=0.009 and p=<0.001, respectively), and night-time PVC proportion was positively correlated with the ratio of low-frequency power (LF)/high-frequency power (HF; r=0.319 [p=0.013]). Multivariate linear regression analysis showed that the number of night-time PVCs was an independent predictor of decreased SDNN (β= -0.446, p=0.030) and increased LF/HF ratio (β=0.027, p=0.038). After PVCs disappeared, SDNN increased significantly and the frequency domain of the square root of the mean of the sum of the squares of differences between adjacent NN intervals, NN50 count divided by the total number of all NN intervals, the time domain of natural logarithm of HF, natural logarithm of LF, and mean 24-hour HR were significantly decreased in the two PVC groups. An increased number of night-time PVCs was accompanied by enhanced cardiac sympathetic activity. After PVCs diminished, both cardiac parasympathetic and sympathetic nervous activity declined.

Transcutaneous electrical nerve stimulation attenuates cardiac sympathetic drive in heart failure: a 123MIBG myocardial scintigraphy randomized controlled trial.

Cardiac sympathetic overdrive provides inotropic support to the failing heart. However, as myocardial insult evolves, this compensatory response impairs contractile function and constitutes an independent mortality predictor and a primary target in the treatment of heart failure (HF). In this prospective, randomized, double-blind, controlled crossover trial, we proposed cervicothoracic transcutaneous electrical nerve stimulation (CTENS) as a nonpharmacological therapy on cardiac sympathetic activity in patients with HF. Seventeen patients with HF were randomly assigned to an in-home CTENS (30 min twice daily, 80-Hz frequency, and 150-μs pulse duration) or a control intervention (Sham) for 14 consecutive days. Following a 60-day washout phase, patients were crossed over to the opposite intervention. The heart-to-mediastinum ratio (HMR) and washout rate (WR) (indexes of sympathetic innervation density and activity from planar 123iodo-metaiodobenzylguanidine myocardial scintigraphy images, respectively), as well as blood pressure (BP) and heart rate (HR), were quantified before and after each intervention. HMR, BP, and HR did not change throughout the study. Nonetheless, CTENS reduced WR (CTENS -4 ± 10 vs. Sham +5 ± 15%, P = 0.03) when compared with Sham. When allocated in two independent groups, preserved (PCSI, HMR > 1.6, n = 10) and impaired cardiac sympathetic innervation (ICSI, HRM ≤1.6, n = 7), PCSI patients showed an important attenuation of WR (-11 ± 9 vs. Sham +8 ± 19%, P = 0.007) after CTENS. Nonetheless, neither Sham nor CTENS evoked changes in WR of the ICSI patients (P > 0.05). These findings indicate that CTENS attenuates the cardiac sympathetic overdrive in patients with HF and a preserved innervation constitutes an essential factor for this beneficial neuromodulatory impact. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Identifier: NCT03354689. NEW & NOTEWORTHY We found that short-term cervicothoracic transcutaneous electrical nerve stimulation (CTENS) attenuates cardiac sympathetic overdrive in patients with heart failure and a preserved autonomic innervation may constitute an essential factor to maximize this beneficial neuromodulatory effect. CTENS then emerges as an alternative noninvasive and nonpharmacological strategy to attenuate exaggerated cardiac sympathetic drive in patients with heart failure.

Assessment of myocardial sympathetic innervation by PET in patients with heart failure: a review of the most recent advances and future perspectives

Life-threatening ventricular arrhythmias (VA) are a major cause of death in patients with congestive heart failure (HF). Among various factors, the sympathetic nervous system may give rise to VA in several pathophysiological pathways due to an impaired function of presynaptic sympathetic nerve terminals. Positron emission tomography (PET) with labeled catecholamine analogues represents a reliable tool to assess the sympathetic innervation activity. This review aims at summarising the most relevant and recent literature findings on the current role of PET in the evaluation of cardiac sympathetic activity in patients with heart failure. A comprehensive literature search strategy using PubMed databases was carried out looking for articles on the role of Positron emission tomography/Computed Tomography (PET/CT) in the assessment of myocardial sympathetic innervation in patients with heart failure. The literature search limited to the last 5 years retrieved 40 papers. Most of the papers dealt with PET studies with 11C-HED. 19 pre-clinical, first-in-human and clinical studies highlighting the current role of PET and future perspectives resulted eligible for inclusion in the present review. The assessment of myocardial sympathetic activity in patients with heart failure with PET will play a pivotal role in clinical practice. Its capability to predict the occurrence of life-threatening VA and the effectiveness of resynchronization therapy makes this technique ideal in the era of personalized medicine.

Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study.

BackgroundIn the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT), heart rate (HR) reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF). The mechanisms by which elevated HR increases mortality are not fully understood.ObjectiveTo assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR.MethodPatients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs) was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy.ResultsMean HR was 83.5±11.5 bpm (range 72 to 104), and seven (43.7%) patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029), higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035) and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001).ConclusionElevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation.

Statin therapy and cardiac sympathetic activity in patients with heart failure: A 123Iodine-metaiodobenzylguanidine myocardial scintigraphy study

Statin therapy and cardiac sympathetic activity in patients with heart failure: A 123Iodine-metaiodobenzylguanidine myocardial scintigraphy study

Statin therapy decreases cardiac sympathetic activity in patients with left ventricular dysfunction: a 123l‐MIBG myocardial scintigraphy study (1169.9)

Convincing animal and human studies indicate that statin therapy decreases renal and muscle sympathetic nerve activity. Reduced cardiac sympathetic drive and innervation have also been reported as pleiotropic consequences of statin therapy in a rat coronary ligation model. This study then investigated whether these results could be translated to a clinical setting of human left ventricular dysfunction. Washout rate (WR) and heart‐to‐mediastinum (H/M) ratio, indexes of cardiac sympathetic activity and innervation density, were obtained from planar 123l‐metaiodobenzylguanidine myocardial scintigraphy images of patients undergoing long‐term statin [30±7 mg/day for at least a month] (7 men and 4 women, NYHA class II‐III, ejection fraction of 45±5%, age of 53±4, and body mass of 83±5 kg) and only standard drug therapy (7 men and 6 women, NYHA class II‐III, ejection fraction of 37±7%, age of 57±2 years, and body mass of 77±7 kg). Resting cardiovascular variables and lipid profiles were similar between groups. Statin users presented lower WR (Statin 29±2% vs. SDT 39±1, P&lt;0.05) whereas early (1.7±0.2 vs. 1.6±0.2, P&gt;0.05) and late (Statin 1.6±0.2 vs. SDT 1.6±0.4, P&gt;0.05) H/M were similar for both groups. Our findings partially extend the results of animal studies and indicate that statin therapy reduces cardiac sympathetic activity in patients with left ventricular dysfunction without changing innervation density.Grant Funding Source: Supported by CAPES, CNPq, FAPERJ, FINEP.

SCINTIGRAPHY WITH 123I-METAIODBENZILGUANIDINE IN EVALUATION OF SYMPATHETIC INNERVATION OF THE LEFT VENTRICULAR IN PATIENTS WITH CORONARY HEART DISEASE AND ATRIAL FIBRILLATION

The aim of this study was assessment of cardiac sympathetic activity in patients with atrial fibrillation by planar scintigraphy with 123I-metaIodbenzilguanidine (123I-MIBG).Material and Methods. The study included 28 (average age (57.4 ± 11.6) years) patients with suspected coronary artery disease. All patients to divide 3 groups: 13 patients (group 1) with paroxysmal AF (PAF),6 patients (group 2) with long-standing persistent AF (LSPAF) and 10 patients with no signs of AF (group 3).Planar imaging was performed to study initial (imaging started 20 minutes after MIBG injection 148 MBq 123I-MIBG) and delayed (imaging started 4 hours after 123I-MIBG injection). For the anterior planar 123I-MIBG images, regions of interest were constructed for the heart and upper mediastinum, and the heart-mediastinal ratio (HMR).Results. The delayed HMR in patients with PAF and LSPAF was significantly lower compared that in patients third group (1.59 ± 0.16, 1.54 ± 0.17 and 1.82 ± 0.11 respectively, p &lt; 0.05). The washout rate of 123I-MIBG in patients with PAF and LSPAF was significantly highest compared that in patients with no signs of AF (33.4 ± 17.5, 29 ± 11.7 and 17.2 ± 9.6 respectively, p &lt; 0.05). In assessment of regional sympathetic activity in patients with LSPAF defect accumulation 123I-MIBG in both the early and delayed scintigrams was significantly higher compared with groups of patients with PAF and without AF.Results of this study indicated, that the patients with atrial fibrillation has of regional LV myocardial changes, according with 123I-MIBG imaging. More sympathetic innervation abnormality was observed in patients with long-standing persistent AF.

Cardioprotective effect of an L/N-type calcium channel blocker in patients with hypertensive heart disease

Left ventricular (LV) diastolic dysfunction is related to increased cardiac sympathetic activity. We investigated the effect of cilnidipine, an L/N-type calcium channel blocker, on LV diastolic function and cardiac sympathetic activity in patients with hypertensive heart disease (HHD) using radionuclide myocardial imaging. Thirty-two frame electrocardiography (ECG) -gated (99m)Tc-sestamibi (MIBI) myocardial single photon emission computed tomography (SPECT), and (123)I-metaiodobenzylguanidine (MIBG) imaging were performed before and 6 months after drug administration in 32 outpatients with HHD. Sixteen of the patients were treated with cilnidipine and the other 16 were treated with nifedipine retard. The parameters for assessing LV diastolic function evaluated using ECG-gated (99m)Tc-MIBI SPECT were peak filling rate (PFR), first-third filling rate (1/3FR), and time to peak filling (TPF). Cardiac sympathetic activity was assessed as early and delayed heart to mediastinum (H/M) ratios and a washout rate (WR), using (123)I-MIBG imaging. The PFR and 1/3FR significantly increased after 6 months of treatment with cilnidipine (p<0.05 for both), but did not with nifedipine retard. The H/M ratios significantly increased (p<0.05 for both) in conjunction with a decreased WR (p<0.05) in the cilnidipine group. Moreover, a significant positive correlation was seen between the rate of change in PFR and the rate of change in early and delayed H/M ratios in the cilnidipine group (p<0.05 for both). The same results were obtained for the relationship between the rate of change in 1/3FR and the rate of change in H/M ratios (p<0.05 for both). However, no such relationship was seen in the nifedipine group. These data indicate that cilnidipine seems to suppress cardiac sympathetic overactivity via blockade of N-type calcium channels and improves LV diastolic function in patients with HHD.

Effects of Sildenafil on Cardiac Sympathetic Activity in Patients with Chronic Heart Failure

Purpose: Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure (CHF) is limited and the impact of phosphodiesterase V inhibition on sympathetic activity in this population has not been evaluated. Methods: Eight patients with CHF secondary to dilated cardiomyopathy were studied. They were instrumented with pulmonary artery, femoral artery, and coronary sinus thermodilution catheters. Cardiac sympathetic activity was measured by the cardiac norepinephrine spillover (CANESP) technique. Hemodynamics and CANESP were determined at baseline and in response to a steady state infusion of sildenafil. Results: The mean age was 59±6 yr and their EF was 24±4%. Sildenafil was given as bolus of 2.6±0.1mg followed by an infusion of 0.8±0.1mg over 20 minutes. Sildenafil caused a significant reduction in right atrial (6±1 vs. 3±1 mmHg, P<0.006), mean pulmonary artery (29±4 vs. 20±3 mmHg, P<0.002), and mean arterial pressures (75±2 vs. 69±1 mmHg, P<0.008). Heart rate and cardiac output did not change. Despite the fall in arterial pressure the infusion of sildenafil was associated with a significant reduction in CANESP (305±36 vs. 235±37 pmol/min, P<0.02). Conclusion: Sildenafil infusion was associated with a significant reduction in cardiac sympathetic activity. These data confirm that the acute administration Sildenafil has modest, beneficial hemodynamic effects in patients with CHF and is not associated with an increase in sympathetic activity directed toward the heart muscle.

Twenty-Four-Hour QT Interval Variability: Increased QT Variability during Sleep in Patients with Panic Disorder

Recent studies on beat-to-beat QT interval variability (QTV) have shown that it can be used as a noninvasive measure of cardiac repolarization lability. It is also a predictor of sudden cardiac death and is higher in patients with anxiety and depression. This study examined the diurnal measures in QTV in 32 normal adults and 22 patients using 24-hour electrocardiogram records. We obtained 8 5-min segments of ECG sampled at 1,000 Hz from the 24-hour records. Our results show that QTV measures at nighttime are significantly higher in patients with panic disorder compared with controls. These findings demonstrate blunted diurnal changes in ventricular repolarization lability in patients resulting in a higher QT variability index during sleep. We speculate that these effects may relate to a relative increase in cardiac sympathetic activity in patients with panic disorder, and may contribute to the increased risk for cardiac mortality in patients with anxiety.

The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure

ObjectivesThe goal of this work was to study the effects of short-term infusion of dobutamine on efferent cardiac sympathetic activity. BackgroundIncreased efferent cardiac sympathetic activity is associated with poor outcomes in the setting of congestive heart failure (CHF). Dobutamine is commonly used in the therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta-receptors, may increase cardiac sympathetic activity. MethodsSeven patients with normal left ventricular (LV) function and 13 patients with CHF were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) before and during an intravenous infusion of dobutamine titrated to increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. ResultsSystemic arterial pulse pressure increased significantly in response to dobutamine in the normal LV function group (74 ± 3 mm Hg to 85 ± 3 mm Hg, p = 0.005) but remained unchanged in the CHF group. Dobutamine caused a significant decrease in LV end-diastolic pressure in the CHF group (14 ± 2 mm Hg to 11 ± 2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal LV function group, CANESP did not change in response to dobutamine (75 ± 22 pmol/min vs. 72 ± 22 pmol/min, p = NS). In contrast, dobutamine infusion was associated with a significant reduction in CANESP in patients with CHF (199 ± 43 pmol/min to 128 ± 30 pmol/min, p < 0.0009). ConclusionsDobutamine infusion caused a significant sympatholytic response in patients with CHF. This sympathetic withdrawal response is probably related to reduction of LV filling pressures and/or activation of ventricular mechanoreceptors with dobutamine infusion.

Cardiac sympathetic activity as measured by myocardial 123-I-metaiodobenzylguanidine uptake and heart rate variability in idiopathic dilated cardiomyopathy

In patients with idiopathic dilated cardiomyopathy (IDC) the increased sympathetic activity owing to chronic congestive heart failure leads to an imbalance of cardiac autonomic tone, as reflected by decreased heart rate variability (HRV). Iodine-123-metaiodobenzylguanidine (123-I-MIBG), which has the same affinity for sympathetic nerve endings as norepinephrine, can be used to assess the integrity and function of the cardiac sympathetic nervous system. The aim of the present study was to measure cardiac sympathetic activity by assessing 123-I-MIBG uptake compared with HRV in patients with IDC. In 12 patients with IDC and mild to moderate heart failure, myocardial MIBG uptake was calculated from the myocardial (M) to left ventricular cavity (C) voxel values density ratio and the 123-I activity in a blood sample as a reference (= M/C ratio) using a double radionuclide study with 123-I-MIBG and technetium-99m-MIBI. To investigate the relation between myocardial MIBG uptake and HRV in time domain, the linear regression between the M/C ratio, a new scintigraphic parameter, and the mean RR interval or the HRV triangular index, respectively, was determined. A significant correlation between the M/C ratio and mean RR interval (r = 0.52; p = 0.016) or M/C ratio and HRV triangular index (r = 0.76; p = 0.003), respectively, was found. Thus, the significant correlation between the M/C ratio and HRV indicate that they are both suitable noninvasive methods for evaluating cardiac sympathetic activity in patients with IDC and, furthermore, favor the view that there is evidence of a relation between HRV and the disorder of the cardiac presynaptic sympathetic nerve endings as demonstrated by a reduced M/C ratio.

Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy

Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy

Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy.

Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased sympathetic tone. However, previous studies in patients with hypothyroidism have suggested that increased plasma noradrenaline (NA) levels represent enhanced general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in hypothyroidism has not been clarified. To evaluate CSA in patients with hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed in eight patients with hypothyroidism before therapy and in ten normal control patients. Planar images were obtained at 15 min and 4 h after injection of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was also measured, and echocardiography was performed in all patients. Those patients with hypothyroidism in the euthyroid state after medical therapy were also evaluated in a similar manner. Left ventricular ejection fraction, measured by echocardiography, did not differ significantly between the groups. NA, MU and MC were significantly higher in patients with hypothyroidism than in controls, and all parameters were decreased after therapy. MC was well correlated with NA in hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in patients with hypothyroidism, in parallel with the enhanced general sympathetic activity.

Digoxin reduces cardiac sympathetic activity in severe congestive heart failure

Objectives. This study evaluated the effect of digoxin on cardiac sympathetic activity in patients with congestive heart failure.Background. Digoxin favorably alters autonomic tone in heart failure. Whether it reduces cardiac sympathetic drive in the setting of heart failure is unknown.Methods. Digoxin (0.25 mg intravenously) was administered to 12 patients with severe heart failure and elevated left ventricular end-diastolic pressure (> 14 mm Hg, Group A), 5 patients with less severe heart failure who had normal left ventricular end-diastolic pressure (⩽14 mm Hg, Group B) and 6 patients with normal ventricular function. Seven additional patients with heart failure were studied as a time control group. Cardiac and total body morepinephrine spillover, systemic arterial pressure, left ventricular filling pressure and peak positive first derivative of left ventricular pressure were all assessed before and 30 min after administration of digoxin.Results. In Group A there were no changes in hemodynamic variables or total body norepinephrine spillover after digoxin administration; however, there was a significant reduction in cardiac norepinephrine spillover (263 ± 70 to 218 ± 62 pmol/min, mean ± SEM, p < 0.001). In contrast, in Group B, digoxin caused a significant increase in cardiac norepinephrine spillover that was not associated with any hemodynamic changes or a change in total body spillover. There were no hemodynamic or spillover changes in the time control or normal ventricular function group.Conclusions. Digoxin, in the absence of detectable inotropic or hemodynamic effects, caused a reduction in cardiac norepinephrine spillover in patients with heart failure who had elevated filling pressures. This finding suggests a potentially beneficial primary autonomic action of digoxin in patients with severe heart failure.

Evidence of a Selective Increase in Cardiac Sympathetic Activity in Patients with Sustained Ventricular Arrhythmias

Although enhanced efferent cardiac sympathetic nervous activity has been proposed as an important factor in the genesis of ventricular arrhythmias and sudden cardiac death, direct clinical evidence has been lacking. We measured the rates of total and cardiac norepinephrine spillover into the plasma, which reflect respectively overall and cardiac sympathetic nervous activity, in 12 patients who had recovered from a spontaneous, sustained episode of ventricular tachycardia or ventricular fibrillation outside the hospital 4 to 48 days earlier. The results were compared with those from three age-matched reference groups without a history of ventricular arrhythmias: 12 patients with coronary artery disease, 6 patients with chest pain but normal coronary arteries, and 12 healthy, normal subjects. The patients who had had ventricular arrhythmias had reduced left ventricular ejection fractions, as compared with the patients with coronary artery disease or chest pain (mean [+/- SE], 46 +/- 3 percent vs. 58 +/- 4 percent and 69 +/- 5 percent, respectively; P less than 0.003). The rates of total norepinephrine spillover into the plasma were similar in the three reference groups, but 80 percent higher in the patients with ventricular arrhythmias (P less than 0.005). The rate of cardiac norepinephrine spillover was 450 percent higher in these patients (176 +/- 39 pmol per minute, as compared with 32 +/- 8 pmol per minute in the normal subjects; P less than 0.001), a disproportionate increase relative to the increase in total spillover, which indicated selective activation of the cardiac sympathetic outflow. This increase in cardiac norepinephrine spillover was probably caused by a reduction in left ventricular function. These results suggest that in some patients major ventricular arrhythmias are associated with and perhaps caused by sustained and selective cardiac sympathetic activation. We speculate that depressed ventricular function was present before the ventricular arrhythmia occurred, and that this resulted in reflex cardiac sympathetic activation, which in turn contributed to the genesis of the arrhythmia.