Sonia Velez-Roa

Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension

Background—This study tested the hypothesis that sympathetic nerve activity is increased in pulmonary artery hypertension (PAH), a rare disease of poor prognosis and incompletely understood pathophysiology. We subsequently explored whether chemoreflex activation contributes to sympathoexcitation in PAH. Methods and Results—We measured muscle sympathetic nerve activity (MSNA) by microneurography, heart rate (HR), and arterial oxygen saturation (Sao2) in 17 patients with PAH and 12 control subjects. The patients also underwent cardiac echography, right heart catheterization, and a 6-minute walk test with dyspnea scoring. Circulating catecholamines were determined in 8 of the patients. Chemoreflex deactivation by 100% O2 was assessed in 14 patients with the use of a randomized, double-blind, placebo-controlled, crossover study design. Compared with the controls, the PAH patients had increased MSNA (67±4 versus 40±3 bursts per minute; P<0.0001) and HR (82±4 versus 68±3 bpm; P=0.02). MSNA in the PAH patients was correlated with HR (r=0.64, P=0.006), Sao2 (r=−0.53, P=0.03), the presence of pericardial effusion (r=0.51, P=0.046), and NYHA class (r=0.52, P=0.033). The PAH patients treated with prostacyclin derivatives had higher MSNA (P=0.009), lower Sao2 (P=0.01), faster HR (P=0.003), and worse NYHA class (P=0.04). Plasma catecholamines were normal. Peripheral chemoreflex deactivation with hyperoxia increased Sao2 (91.7±1% to 98.4±0.2%; P<0.0001) and decreased MSNA (67±5 to 60±4 bursts per minute; P=0.0015), thereby correcting approximately one fourth of the difference between PAH patients and controls. Conclusions—We report for the first time direct evidence of increased sympathetic nerve traffic in advanced PAH. Sympathetic hyperactivity in PAH is partially chemoreflex mediated and may be related to disease severity.

Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension.

RATIONALE The sympathetic nervous system has been reported to be activated in pulmonary arterial hypertension (PAH). OBJECTIVES We investigated the prognostic significance of muscle sympathetic nervous system activity (MSNA) in PAH. METHODS Thirty-two patients with PAH were included in the study and underwent a measurement of MSNA over a 6-year period of time. They had undergone a concomitant evaluation of New York Heart Association (NYHA) functional class, a 6-minute walk distance (6MWD), an echocardiographic examination, and a right heart catheterization for diagnostic or reevaluation purposes. The median follow-up time was 20.6 months (interquartile range, 45.8 mo). Clinical deterioration was defined by listing for transplantation or death. MEASUREMENTS AND MAIN RESULTS Seventeen patients presented with clinical deterioration. As compared with the 15 others, they had an increased MSNA (80 +/- 12 vs. 52 +/- 18 bursts/min; P < 0.001) and heart rate (88 +/- 17 vs. 74 +/- 12 bpm; P = 0.01), a lower 6MWD (324 +/- 119 vs. 434 +/- 88 m; P < 0.01) and a deteriorated NYHA functional class (3.6 +/- 0.5 vs. 2.9 +/- 0.8; P < 0.001). The hemodynamic variables were not different. MSNA was directly related to heart rate and inversely to 6MWD. A univariate analysis revealed that increased MSNA and heart rate, NYHA class IV, lower 6MWD, and pericardial effusion were associated with subsequent clinical deterioration. A multivariate analysis showed that MSNA was an independent predictor of clinical deterioration. For every increase of 1 burst/minute, the risk of clinical deterioration during follow-up increased by 6%. CONCLUSIONS Sympathetic nervous system activation is an independent predictor of clinical deterioration in pulmonary arterial hypertension.

Regression of Left Ventricular Hypertrophy After Arteriovenous Fistula Closure in Renal Transplant Recipients: A Long-Term Follow-Up

The long‐term effects of hemodialysis arteriovenous fistula (AVF) closure on left ventricular (LV) morphology are unknown. Using echocardiography, we prospectively studied 17 kidney transplant recipients before, 1, and, 21 months after AVF closure (mean fistula flow 1371 ± 727 mL/min). Eight kidney transplant recipients with a patent AVF, matched for age, time after AVF creation, and time after transplantation, served as controls. LV mass index (LVMI) decreased from 139 ± 44 g/m2 before AVF closure to 127 ± 45 g/m2 and 117 ± 40 g/m2 at 1 and 21 months post‐closure, respectively (p < 0.001), but remained unchanged in controls. LV hypertrophy prevalence (LVMI > 125 g/m2) decreased from 65% before, to 41% early, and 18%, late, after surgery (p = 0.008), mostly from a decrease in LV end‐diastolic diameter. Consequently, the prevalence of LV concentric remodeling (relative wall thickness > 0.45 without hypertrophy) increased from 12% before, to 35% early, and 65% late, after surgery (p = 0.003). Diastolic arterial blood pressure increased from 78 ± 15 mmHg before, to 85 ± 13 mmHg early, and 85 ± 10 mmHg late, after surgery (p < 0.015).In conclusion, closure of large and/or symptomatic AVF induces long‐term regression of LV hypertrophy. However, residual concentric remodeling geometry as well as diastolic blood pressure increase may blunt the expected beneficial cardiac effects of the procedure.

SIGNIFICANCE OF ST-SEGMENT ELEVATIONS IN POSTERIOR CHEST LEADS (V7 TO V9) IN PATIENTS WITH ACUTE INFERIOR MYOCARDIAL INFARCTION

We read with much interest the article by S. Matetzky et al. (1). It is a valid study emphasizing the value of posterior chest lead (V7 to V9) in early identification of patients with larger inferior myocardial infarction (IMI) exhibiting more benefit from effective thrombolysis. We also performed 16 lead ECGs (12 leads, V7 V8 V9 and V4 R) in a series of 66 first IMIs admitted within six hours of chest pain (2). Like Matetzky et al. we observed significantly lower radionuclide left ventricular ejection fraction, higher peak creatine kinase levels and more frequent 12 lead-ECG pattern of posterior wall extension when ST elevation was greater than 0.05 mV in lead V9. Unlike the authors we did not observe any difference in the in-hospital clinical course. We explained the observation by the fact that right ventricular infarction (RVI) was significantly more frequent in our control group. In spite of the important role of RVI in IMI (3), the authors did not record V4 R and they did not discuss the possible influence of RVI on the prognosis while right coronary artery was more frequently involved in their control group (63% and 90%, p , 0.003). They also did not discuss the balance of other early 12 lead-ECG prognostic markers (4) among the groups, which could have influenced the results. We believe that independent prognostic value of posterior chest leads (V7 to V9) in IMI has to be assessed in a multivariate analysis combining initial 16 lead ECG variables and clinical predictors of events before recommending its systematic use in IMI.

Dobutamine potentiates the peripheral chemoreflex in patients with congestive heart failure.

BACKGROUND beta-Adrenergic agonists may increase chemoreflex sensitivity to hypoxia in normal humans. Chemoreflex function is important in the pathophysiology of heart failure. Whether the beta-1 agonist dobutamine, which is frequently administered to patients with heart failure, alters their chemoreflex sensitivity is not known. METHODS We tested the hypothesis that dobutamine increases chemoreflex sensitivity in patients with congestive heart failure (CHF) using a randomized, double-blinded, placebo-controlled study design. We assessed the influence of dobutamine on minute ventilation and hemodynamics during normoxic breathing and during peripheral chemoreflex deactivation by hyperoxia (100% O(2)) in 9 patients with CHF. RESULTS Dobutamine increased minute ventilation in patients with CHF (9.4+/-0.9 versus 8.4+/-0.7 L/min, P=.005) during normoxia. Peripheral chemoreflex deactivation by hyperoxia suppressed the ventilatory effects of dobutamine (10.4+/-1.4 L/min for dobutamine versus 10.0+/-1.2 L/min for placebo, P=.34). CONCLUSIONS Dobutamine increases ventilation during normoxia, but not during hyperoxia in patients with CHF. We conclude that dobutamine enhances peripheral chemoreflex sensitivity in patients with congestive heart failure.

Effects of low-dose dopamine on ventilation in patients with chronic obstructive pulmonary disease

Background  Dopamine plays an important role in the regulation of respiration and low‐dose dopamine infusion is associated with a decreased respiratory drive response to hypoxia in animals and humans. The effects of dopamine on ventilation in patients with chronic obstructive pulmonary disease (COPD) is unknown. We tested the hypothesis that dopamine inhibits ventilation in patients with COPD.