Direct evidence of sympathetic hyperactivity in patients with vasospastic angina.

BACKGROUND: The autonomic nervous system is reported to be involved in the pathogenesis of vasospastic angina (VSA). Studies based on heart rate variability analysis have shown conflicting results with both a reduction and an enhancement of sympathetic nervous system (SNS) activity in patients with Prinzmetal's variant angina, but direct assessment has never been performed. The aim of our study was to evaluate the SNS activity using microneurography in patients with VSA. METHODS AND RESULTS: The SNS was evaluated by measuring the muscle sympathetic nerve activity (MSNA) with microneurography in 15 patients with VSA confirmed by positive ergonovine provocation test and 15 controls subjects negative for the provocation test. Over the baseline period, SNS activity was higher in patients with VSA compared with control patients (56.8 ± 5 vs. 49.3 ± 6.3 burst/min, p < 0.001, respectively). During mental stress, SNS activity increased significantly only in patients with VSA, which still presented a higher SNS activity than control patients (66.1 ± 7.2 vs. 53.6 ± 8.7 burst/min; p < 0.001, respectively). Furthermore only VSA patients showed significant hemodynamic modifications with an increase in mean arterial blood pressure (96.2 ± 13.4 vs. 86.6 ± 9.6 mmHg in VSA patients and control subjects, respectively; p < 0.05). CONCLUSION: Our results provide the first direct evidence of lasting increased sympathetic activity that is worsened by mental stress in patients with VSA. These results suggest that SNS participate to the pathogenesis of VSA by enhancing coronary vascular tone.

Towards a less invasive approach to the early goal-directed treatment of septic shock in the ED.

INTRODUCTION: Early goal-directed therapy (EGDT) in septic shock defined by Rivers et al was proven to reduce mortality and validated by observational studies. However, criticism is centered in particular on the early requirement of a central venous catheter (CVC) and on central venous pressure (CVP) as an indicator of volume responsiveness. The present study is a pivotal study to investigate the reliability of a less invasive approach, which uses inferior vena cava (IVC) and lung ultrasounds (US) to guide the infusion of fluids and lactate clearance to monitor tissue perfusion. METHODS: We enrolled 51 patients with septic shock. As a marker of preload optimization, we measured IVC collapse in place of CVP and serum lactate clearance in place of central venous oxygen saturation as a marker of tissue perfusion. As outcomes, we considered the accomplishment of the noninvasive EGDT goals, the number of patients treated without the need of a CVC, the amount of fluids administered in the first 6 hours, the development of pulmonary edema, and the overall mortality rate. RESULTS: Inferior vena cava US evaluation resulted feasible in 92% of patients. Lung US was performed in 100% of cases. In the first 6 hours, only 61.7% of patients received a CVC, an average of 5.5 L of crystalloids were administered, and only 4 patients developed clinical overt pulmonary edema. Mortality was 34% at 28 days and 38.3% at 60 days. CONCLUSIONS: Our approach to resuscitation in septic shock appears feasible in the emergency department and needs further study with a randomized controlled trial.

Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy.

BACKGROUND: The exact pathophysiology of Tako-Tsubo cardiomyopathy (TTC) remains unknown but a role for sympathetic hyperactivity has been suggested. Up to now, no direct evidence of sympathetic nerve hyperactivity has been established nor involvement of sympathetic baroreflex identified. The aim of our study was to determine, by direct sympathetic nerve activity (SNS) recording if sympathetic nervous system activity is increased and spontaneous baroreflex control of sympathetic activity reduced in patients with TTC. METHODS: We included 13 patients who presented with TTC and compared their SNS activity and spontaneous baroreflex control of sympathetic activity with that of 13 control patients with acutely decompensated chronic heart failure. SNS activity was evaluated by microneurography, a technique assessing muscle sympathetic nerve activity (MSNA). Spontaneous baroreflex control of sympathetic activity was evaluated as the absolute value of the slope of the regression line representing the relationship between spontaneous diastolic blood pressure values and concomitant SNS activity. Control patients were matched for age, sex, left ventricular ejection fraction and creatinine clearance. RESULTS: The mean age of the patients with TTC was 80 years, all patients were women. There were no significant differences between the two groups of patients for blood pressure, heart rate or oxygen saturation level. TTC patients presented a significant increase in sympathetic nerve activity (MSNA median 63.3 bursts/min [interquartile range 61.3 to 66.0] vs median 55.7 bursts/min [interquartile range 51.0 to 61.7]; p = 0.0089) and a decrease in spontaneous baroreflex control of sympathetic activity compared to matched control patients (spontaneous baroreflex control of sympathetic activity median 0.7%burst/mmHg [interquartile range 0.4 to 1.9] vs median 2.4%burst/mmHg [interquartile range 1.8 to 2.9]; p = 0.005). CONCLUSIONS: We report for the first time, through direct measurement of sympathetic nerve activity, that patients with TTC exhibit elevated SNS activity associated with a decrease in spontaneous baroreflex control of sympathetic activity. These data may explain the pathophysiology and clinical presentation of patient with TTC.

Transcatheter aortic valve implantation reduces sympathetic activity and normalizes arterial spontaneous baroreflex in patients with aortic stenosis.

OBJECTIVES: This study sought to measure muscle sympathetic nerve activity (MSNA) in patients with aortic stenosis (AS) before and after transcatheter aortic valve implantation (TAVI) and to compare MSNA with that of control patients. BACKGROUND: TAVI is an emerging therapeutic option in patients with severe AS at high risk of open heart surgery. Whether patients with AS have increased sympathetic activity remains to be established, and the effects of TAVI on the sympathetic nervous system are also unknown. METHODS: We prospectively enrolled 14 patients with severe symptomatic AS treated by TAVI. Fourteen control patients matched for age, body mass index, and unscathed of AS were also included. All patients underwent MSNA and arterial baroreflex gain assessment at baseline and 1 week after TAVI for AS patients. RESULTS: Patients with AS had lower blood pressure (BP) levels, a significant increase in MSNA (61.0 ± 1.7 burst/min vs. 55.4 ± 1.4 burst/min; p < 0.05), and a decrease in arterial baroreflex gain (2.13 ± 0.14% burst/mm Hg vs. 3.32 ± 0.19% burst/mm Hg; p < 0.01) compared with matched control patients. The TAVI procedures induced an increase in BP associated with a significant decrease in MSNA (from 61.0 ± 1.7 burst/min to 54.1 ± 1.0 burst/min; p < 0.01) and was associated with a significant increase in arterial baroreflex gain (from 2.13 ± 0.14% burst/mm Hg to 3.49 ± 0.33% burst/mm Hg; p < 0.01). CONCLUSIONS: We report for the first time, through direct measurement of nerve activity, that patients with AS have increased sympathetic nervous system activity associated with a decrease in sympathetic baroreflex gain and that TAVI normalizes these parameters. This study provides evidence of a new beneficial effect of TAVI, namely, normalization of sympathetic nervous system hyperactivity.

High-intensity interval exercise improves vagal tone and decreases arrhythmias in chronic heart failure.

PURPOSE: Autonomic dysfunction including sympathetic activation and vagal withdrawal has been reported in patients with chronic heart failure (CHF). We tested the hypotheses that high-intensity interval exercise (HIIE) in CHF patients would enhance vagal modulation and thus decrease arrhythmic events. METHODS: Eighteen CHF patients underwent a baseline assessment (CON) and were then randomized to a single session of HIIE and to an isocaloric moderate-intensity continuous exercise (MICE). We evaluated the HR, HR variability parameters, and arrhythmic events by 24-h Holter ECG recordings after HIIE, MICE, and CON sessions. RESULTS: We found that HR was significantly decreased after HIIE (68 ± 3 bpm, P < 0.01) when compared with CON and MICE values (71.1 ± 2 and 69 ± 3 bpm, respectively). HIIE led to a significant increase in normalized high-frequency power (35.95% ± 2.83% vs 31.56% ± 1.93% and 24.61% ± 2.62% for CON and MICE, respectively, P < 0.01). Both exercise conditions were associated with an increase in very low frequency power comparative to CON. After HIIE, premature ventricular contractions were significantly decreased (531 ± 338 vs 1007 ± 693 and 1671 ± 1604 for CON and MICE, respectively, P < 0.01). An association was found between the changes in premature ventricular contraction and the changes in low-frequency/high-frequency ratio (r = 0.66, P < 0.01) in patients exposed to HIIE. CONCLUSION: We demonstrate that a single session of HIIE improves autonomic profile of CHF patients, leading to significant reductions of HR and arrhythmic events in a 24-h posttraining period. Cardioprotective effects of HIIE in CHF patients need to be confirmed in a larger study population and on a long-term basis.

Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity.

BACKGROUND: We sought to assess whether cardiorenal anemia syndrome (CRAS) in chronic heart failure (CHF) patients contributes to sympathetic overactivity through modulation of sympathetic reflexes. METHODS AND RESULTS: We prospectively studied 15 patients with CRAS and CHF and 15 control CHF patients, matched for age, gender distribution, type of cardiomyopathy, left ventricular ejection fraction (LVEF) and BMI. We compared muscle sympathetic nerve activity (MSNA) and the effect of peripheral chemoreflex deactivation on MSNA in both groups. We also compared sympathetic baroreflex function, assessed by the slope of the relationship between MSNA and diastolic blood pressure in both groups and while peripheral chemoreflexes were (by breathing 100% oxygen for 15 min) or not deactivated. Baseline MSNA was significantly elevated in CHF patients with CRAS compared with control CHF patients (83.1 ± 4.6 versus 64.9 ± 2.9 bursts/100 heart beats; P<0.05) and sympathetic baroreflex impaired (2.69 ± 0.44 vs 5.25 ± 0.60%bursts/mmHg; P<0.01). Chemoreflex deactivation with administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity (77.8 ± 4.7 versus 82.1 ± 4.9 bursts/100 heart beats; P<0.01) and to an increase in sympathetic baroreflex function (2.77 ± 0.45 vs 5.63 ± 0.73%bursts/mmHg; P<0.01) in patients with CRAS and CHF. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamic or sympathetic baroreflex function in control CHF patients. CONCLUSIONS: CRAS in CHF patients is associated with elevated sympathetic activity mediated by both tonic activation of peripheral chemoreflex and baroreflex impairment.

Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure.

BACKGROUND: Chemoreflex-mediated sympathetic activation contributes to both initiation and progression of chronic heart failure (CHF). METHOD: To study the direct role of increased peripheral chemosensitivity in reducing sympathetic baroreflex function in CHF patients, we compared sympathetic baroreflex function, assessed by the slope of the relationship between muscle sympathetic nerve activity (MSNA) and DBP, in CHF patients with augmented (n = 18) and normal (n = 20) peripheral chemosensitivity. Using a double-blind, randomized, vehicle-controlled study, we examined the effect of chemoreflex deactivation (by breathing 100% oxygen for 15 min) on sympathetic baroreflex function in CHF patients with elevated and with normal chemosensitivity. RESULTS: Baseline MSNA was elevated (60.6 ±â€Š3.2 vs. 48.9 ±â€Š3.7 bursts/min, P < 0.05) and sympathetic baroreflex function impaired (3.06 ±â€Š0.55 vs. 5.51 ±â€Š0.69 % bursts/mmHg, P < 0.05) in CHF patients with augmented peripheral chemosensitivity compared with controls. Administration of 100% oxygen led to a significant decrease in MSNA (from 60.5 ±â€Š3.2 to 52.6 ±â€Š3.2 bursts/min, P < 0.001) and increase in sympathetic baroreflex (from 2.95 ±â€Š0.56 to 6.18 ±â€Š0.77, P < 0.001) in CHF patients with enhanced chemoreflex sensitivity. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamics or sympathetic baroreflex function in CHF patients with normal chemosensitivity. CONCLUSION: We report for the first time that increased peripheral chemoreflex sensitivity directly decreases sympathetic baroreflex function in CHF patients. This interaction contributes to sympathetic overactivity and blunted sympathetic baroreflex function of CHF patients and may explain how chemoreceptors contribute to the bad prognosis of CHF patients.