Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

Prognostic value of circulating levels of endothelin-1 in patients after acute myocardial infarction undergoing primary coronary angioplasty

BACKGROUND: The link between increased circulating level of endothelin (ET)-1 and adverse clinical outcomes after acute myocardial infarction (AMI) has been established. Current studies demonstrate that reperfusion therapy by either thrombolysis or primary percutaneous coronary intervention (PCI) can salvage myocardium, improving survival of AMI patients. However, whether reperfusion therapy by primary PCI can prevent the adverse effect of ET-1 on clinical outcomes in patients after AMI remains unclear. Therefore, this study examined the predictive value of circulating ET-1 levels on 30-day outcomes in ST-segment elevated AMI treated with primary PCI. METHODS AND RESULTS: We conducted a prospective cohort study of 186 consecutive patients with ST-segment elevated AMI of onset < 12 h who underwent primary PCI. Blood samples for plasma concentration of ET-1 were collected in the catheterization laboratory following vascular puncture. Patients were classified into a high group (group 1, ET-1 level >or= 0.632 pg/mL, n = 93) and a low group (group 2, ET-1 level < 0.632 pg/mL, n = 93) according to the median value of ET-1 after AMI. Univariate analysis demonstrated that the 30-day composite major adverse clinical outcomes (MACO) [advanced Killip score >or= 3], severe congestive heart failure (CHF) [New York Heart Association functional class 4], and 30-day mortality were strongly associated with high ET-1 level (>or= 0.632 pg/mL; p < 0.0001), unsuccessful reperfusion (final Thrombolysis in Myocardial Infarction flow 相似文献   

N-terminal pro-brain natriuretic peptide and renal insufficiency as predictors of mortality in pulmonary hypertension

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a byproduct of the brain natriuretic peptide (BNP) that was shown to be of prognostic value in pulmonary hypertension (PH). The role of NT-proBNP in PH has to be determined, especially under the influence of renal impairment that might lead to an accumulation of the peptide, and may be a sign of increased mortality per se. METHODS: We assessed NT-proBNP, BNP, renal function, and hemodynamic parameters (during right-heart catheterization) in 118 consecutive patients with isolated PH, excluding left-heart disease. Depending on the calculated creatinine clearance, patients were classified into different groups of renal function. Correlation analysis was performed on all key parameters. Results were then compared between the levels of renal function. The prognostic value of each parameter was assessed during a mean follow-up period of 10 months. RESULTS: Twenty-two patients (approximately 19%) had significantly impaired renal function (creatinine clearance < 60 mL/min). Although the overall levels of NT-proBNP were correlated with hemodynamics, we observed no correlation in the group with significant renal dysfunction. Moreover, NT-proBNP was related to creatinine clearance. Finally, NT-proBNP and renal insufficiency were independent predictors of death during univariate and multivariate analysis, whereas BNP only predicted mortality in univariate analysis. CONCLUSIONS: The diagnostic accuracy of NT-proBNP as a parameter of the hemodynamic status is diminished by renal function. However, NT-proBNP could be superior to BNP as a survival parameter in PH because it integrates hemodynamic impairment and renal insufficiency, which serves as a sign of increased mortality per se.     

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

CT scan findings in chronic thromboembolic pulmonary hypertension: predictors of hemodynamic improvement after pulmonary thromboendarterectomy

STUDY OBJECTIVES: The aim was to correlate CT scan findings with hemodynamic measurements in patients who had undergone pulmonary thromboendarterectomy (PTE) and to evaluate whether CT scan findings can help to predict surgical outcome.Patients and method: Sixty patients who underwent PTE and preoperative helical CT scanning were included. Preoperative and postoperative hemodynamics were correlated with preoperative CT imaging features. RESULTS: The diameter of the main pulmonary artery (PA) and the ratio of the PA and the diameter of the ascending aorta correlated with preoperative mean pulmonary artery pressure (PAP) [r = 0.42; p < 0.001; and r = 0.48; p < 0.0001, respectively]. There was a significant correlation of subpleural densities with preoperative pulmonary vascular resistance (PVR) [r = 0.44; p < 0.001] and of the number of abnormal perfused lobes with preoperative PAP (r = 0.66; p < 0.0001) and PVR (r = 0.76; p < 0.0001). Postoperative PVR correlated negatively with the presence and extent of central thrombi (r = -0.36; p = 0.007) and dilated bronchial arteries (p = 0.03) seen on preoperative CT scans. Sixty percent of patients (3 of 5 patients) without visible central thromboembolic material on CT scans had an inadequate hemodynamic improvement in contrast to 4% of patients (2 of 51 patients) with central thrombi (p = 0.003). Preoperative PVR (r = 0.31; p = 0.018) and the extent of abnormal lung perfusion (r = 0.37; p = 0.007) and of subpleural densities (r = 0.32; p = 0.017) were positively correlated with postoperative PVR. CONCLUSIONS: In patients with thromboembolic pulmonary hypertension, CT scan findings can help to predict hemodynamic improvement after PTE. The absence of central thrombi is a significant risk factor for inadequate hemodynamic improvement.     

Clinical application of tissue Doppler imaging in patients with idiopathic pulmonary hypertension

BACKGROUND: Tissue Doppler (TD) echocardiographic imaging of mitral and tricuspid annulus has been applied to assess right ventricular (RV) and left ventricular (LV) function in many cardiac diseases, but its clinical application, including response to long-term targeted therapy in patients with idiopathic pulmonary hypertension (PH), has not been addressed. METHODS: Seventy patients with idiopathic PH were compared with 35 age-matched control subjects to examine myocardial velocities by TD. Of these, 35 patients underwent repeat imaging after long-term targeted therapy. In addition, 50 consecutive patients with idiopathic PH with simultaneous right-heart catheterization and echocardiography were examined. RESULTS: No significant differences were noted between PH patients and the control group in lateral mitral annulus systolic velocity and early diastolic velocity (Ea) by TD, but septal velocities were significantly lower (p < 0.01). With targeted therapy, myocardial velocities at the septum and RV free wall increased significantly (p < 0.05). Likewise, E/Ea ratio increased, albeit still in the normal range. In all 50 patients with invasive measurements, lateral E/Ea ratio readily identified normal mean pulmonary capillary wedge pressure (PCWP). CONCLUSIONS: TD imaging of the lateral mitral annulus can reliably predict the presence of normal/reduced mean PCWP in patients with idiopathic PH, and track the improvement in RV function and LV filling with long-term targeted therapy.     

Dramatic functional improvement following bariatric surgery in a patient with pulmonary arterial hypertension and morbid obesity

Pulmonary arterial hypertension (PAH) and morbid obesity both dramatically impair functional capacity. New therapies have emerged for both conditions, including pharmaceutical agents for the former and bariatric surgery for the latter. The presence of both conditions simultaneously, however, may limit the applicability and effectiveness of these therapies. We report a case of a morbidly obese patient with severe PAH and functional impairment. A three-drug combination regimen consisting of oral bosentan and sildenafil, and inhaled iloprost produced sufficient hemodynamic improvement to allow for the performance of bariatric surgery. Over the subsequent 7 months, body weight, oxygen requirement, functional class, and 6-min walk distance all improved dramatically despite the persistence of PAH. While such surgery is typically denied to patients with PAH, we suggest that aggressive medical therapy for patients with PAH may allow for its safe performance, and that the clinical improvement resulting from the subsequent weight loss may be quite dramatic.     

Long-term follow-up of a fenestrated Amplatzer atrial septal occluder in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease, with right-heart failure being the main cause of death. In patients refractory to conventional drug therapy, atrial septostomy can serve as palliative treatment or as a bridge to transplantation. A 41-year-old woman with a 15-year history of PAH associated with a corrected atrial septal defect presented with severe deterioration of symptoms. Echocardiography confirmed reocclusion of an atrial septal stoma that had been created several months before. After performing a repeat atrial septostomy, we implanted a custom-made atrial septostomy device, an Amplatzer septal occluder that had been fenestrated to serve as a custom-made atrial septostomy device. This resulted in an improvement in cardiac output and a marked symptomatic relief. During the 6-year follow-up, the patient was clinically stable with limited but constant exercise tolerance, under specific medical therapy. Repeated echocardiography confirmed long-term patency of the device.     

Simvastatin treatment of pulmonary hypertension: an observational case series

BACKGROUND: Statins confer cardiovascular benefits beyond the reduction of serum cholesterol through antiproliferative and antiinflammatory mechanisms and induction of endothelial nitric oxide expression. In pneumonectomized rats injected with monocrotaline, simvastatin reversed established pulmonary hypertension and conferred a 100% survival advantage. STUDY OBJECTIVES: To evaluate the safety and efficacy of simvastatin for treatment of patients with pulmonary arterial hypertension (PAH). DESIGN: Open-label observational study performed at Stanford University Medical Center. Sixteen patients with primary and secondary causes of PAH, World Health Organization (WHO) classes I (n = 2), II (n = 4), III (n = 3), IV (n = 7), are described. Simvastatin was prescribed at 20 to 80 mg/d and continued in the absence of adverse effects. MEASUREMENTS AND RESULTS: Serial measurements of 6-min walk (6MW) performance, hemodynamics, and echocardiographic estimates of right ventricular systolic pressures (RVSPs) were recorded on each patient. Simvastatin treatment was not associated with hepatic dysfunction, muscle necrosis, or other adverse events. Individual patients demonstrated improvements in 6MW performance, improvements in cardiac output, or decreases in RVSP that may be attributable to simvastatin treatment. Overall, the rate of disease progression appeared to be attenuated, and WHO class IV patients demonstrated improved survival. CONCLUSIONS: Simvastatin treatment appears safe in patients with PAH.     

Right and left ventricular function and pulmonary artery pressure in patients with bronchiectasis

BACKGROUND: Bronchiectasis may have deleterious effects on cardiac function secondary to pulmonary hypertension (PH). This study was designed to assess cardiac function and determine the prevalence of PH in patients with cystic and cylindrical bronchiectasis. METHODS: A cross-sectional study of patients with bronchiectasis diagnosed by CT scan was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between December 2005 and January 2007. Pulmonary function tests were performed, arterial blood gas measurements were made, and cardiac function and systolic pulmonary artery pressure (SPAP) were assessed by echocardiography. RESULTS: Of 94 patients (31% men, n = 29), 62 patients (66%) had cystic bronchiectasis and 32 patients (34%) had cylindrical bronchiectasis. Right ventricular (RV) systolic dysfunction was observed in 12 patients (12.8%), left ventricular (LV) systolic dysfunction was observed in 3 patients (3.3%), and LV diastolic dysfunction was observed in 11 patients (11.7%); all had cystic bronchiectasis. RV dimensions were significantly greater in the cystic bronchiectasis group, and were positively correlated with SPAP (p < 0.0001) and negatively correlated with Pao2 (p < 0.016). Other hemodynamic variables were not different between groups. PH in 31 patients (32.9%) was significantly greater in patients with cystic bronchiectasis compared with cylindrical bronchiectasis (p = 0.04). In cystic bronchiectasis, SPAP was positively correlated with Paco2 (p = 0.001), and inversely correlated with Pao2 (p = 0.03), diffusion capacity of the lung for carbon monoxide percentage (p = 0.02), and FEV1 (p = 0.02). CONCLUSIONS: RV systolic dysfunction and PH were more common than LV systolic dysfunction in bronchiectatic patients. LV diastolic dysfunction was mainly seen in severe PH. We recommend detailed assessment of cardiac function, particularly LV diastolic function, in patients with bronchiectasis.     

Does Endothelin Play a Role in Chemoreception During Acute Hypoxia in Normal Men?

BACKGROUND: The peripheral chemoreceptors are the dominant reflex mechanism responsible for the rise in ventilation and muscle sympathetic nerve activity (MSNA) in response to hypoxia. Animal studies have suggested that endothelin (ET) plays an important role in chemosensitivity. Moreover, several human clinical conditions in which circulating ET levels are increased are accompanied by enhanced chemoreflex sensitivity. Whether ET plays a role in normal human chemosensitivity is unknown. METHODS: We determined whether bosentan, a nonspecific ET receptor antagonist, would decrease chemoreflex sensitivity in 14 healthy subjects. We assessed the effects of bosentan on the response to isocapnic hypoxia, using a randomized, crossover, double-blinded study design. RESULTS: Bosentan increased mean (+/- SEM) plasma ET levels from 1.97 +/- 0.28 to 2.53 +/- 0.23 pg/mL (p = 0.01). Hypoxia increased mean minute ventilation from 6.7 +/- 0.3 to 8+/0.4 L/min (p < 0.01), mean MSNA from 100 to 111 +/- 5% (p < 0.01), mean heart rate from 67 +/- 3 to 86 +/- 3 beats/min (p < 0.01), and mean systolic BP from 116 +/- 3 to 122 +/- 3 mm Hg (p < 0.01). However, none of these responses differed between therapy with bosentan and therapy with placebo (p = 0.26). Bosentan did not affect the mean MSNA responses to the apneas, during normoxia (change from baseline: placebo, 259 +/- 58%; bosentan, 201 +/- 28%; p = 0.17) or during hypoxia (change from baseline: placebo, 469 +/- 139%; bosentan, 329 +/- 46%; p = 0.24). The durations of the voluntary end-expiratory apneas in normoxia and hypoxia, and the subsequent reductions in oxygen saturation, were also similar with therapy using bosentan and placebo (p = 0.42). CONCLUSION: In healthy men, ET does not play an important role in peripheral chemoreceptor activation by acute hypoxia.     

End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension

OBJECTIVES: Primary pulmonary hypertension (PPH) is a pulmonary vasculopathy resulting in exercise intolerance, usually due to dyspnea. We hypothesized that ventilation is increased during exercise in PPH relative to normal because the ventilated lung is underperfused, cardiac output increase is restricted, and arterial hypoxemia may develop. Our aim was to determine the size of the reduction in end-tidal Pco(2) (Petco(2)) as a reflection of the abnormality in ventilatory efficiency and ventilatory drive in PPH patients. METHODS: We performed cardiopulmonary exercise testing (CPET) in 52 PPH patients. All had hemodynamic measurements to confirm the diagnosis of PPH. A subgroup of 29 patients who underwent right-heart catheterization within 50 days of CPET were studied to compare their CPET responses to resting hemodynamics. Nine healthy volunteers matched for age and gender served as CPET control subjects. RESULTS: In PPH patients, the percentage of predicted peak oxygen uptake (Vo(2)) correlated significantly with mean pulmonary artery pressure (mPAP) [r = - 0.59, p = 0.0007, n = 29]. Petco(2) values at rest, anaerobic threshold (AT), and peak Vo(2) were proportionately reduced as percentage of predicted peak Vo(2) decreased (r = 0.66 to 0.72, p < 0.0001, n = 52). Petco(2) values at rest, AT, and peak Vo(2) were also reduced as mPAP increased (r = - 0.51 to - 0.53, p < 0.005, n = 29). In contrast to normal subjects in whom Petco(2) increased from rest to AT, Petco(2) decreased in PPH patients, except for two patients with mild PPH in whom there was no change. Also, Petco(2) increased rather than decreased further at the start of recovery, in contrast to normal. Although usually normal at rest, oxyhemoglobin saturation decreased during exercise in most PPH patients. CONCLUSIONS: In patients with PPH, Petco(2) at rest and exercise is significantly reduced in proportion to physiologic disease severity. The range of values is unusually low. Furthermore, the directional changes of Petco(2) during exercise and early recovery are in the opposite direction of normal.     

Pulmonary Artery Denervation Attenuates Pulmonary Arterial Remodeling in Dogs With Pulmonary Arterial Hypertension Induced by Dehydrogenized Monocrotaline

ObjectivesThis study aimed to investigate sympathetic nerve (SN) ultrastructural changes and hemodynamic and pulmonary artery (PA) pathological improvements by pulmonary arterial denervation (PADN) in animals with pulmonary arterial hypertension (PAH), as well as the underlying mechanisms.BackgroundSN overactivity plays a role in PAH. Previous studies have reported short-term improvements in pulmonary arterial pressure (PAP) and cardiac function by PADN, but PA remodeling and the associated mechanisms remain unclear.MethodsForty dogs were randomly (ratio of 1:3) assigned to the control (intra-atrial injection of N-dimethylacetamide, 3 mg/kg) and test (intra-atrial injection of dehydrogenized-monocrotaline, 3 mg/kg) groups. After 8 weeks, the animals in the test group with a mean PAP >25 mm Hg (n = 20) were randomized (ratio of 1:1) into the sham and PADN groups. At 14 weeks, the hemodynamics, medial wall thickness and PA muscularization, and messenger ribonucleic acid expression of genes in lung tissues were measured. Another 35 PAH dogs were used to measure the SN conduction velocity, electron microscopic assessment, and nerve distribution.ResultsPADN induced significant SN demyelination and axon loss and slowed SN conduction velocity over time, with resulting profound reductions in the mean PAP (23.5 ± 2.3 mm Hg vs. 33.7 ± 5.8 mm Hg), pulmonary vessel resistance (3.5 ± 2.3 Wood units vs. 7.7 ± 1.7 Wood units), medial wall thickness (22.3 ± 3.3% vs. 30.4 ± 4.1%), and full muscularization (40.3 ± 9.3% vs. 57.1 ± 5.7%) and increased nonmuscularization (29.8 ± 6.1% vs. 12.9 ± 4.9%) compared with the Sham group (all p < 0.001). PADN inhibited the messenger ribonucleic acid expression of genes correlated with inflammation, proliferation, and vasoconstriction.ConclusionsPADN induces permanent SN injury and subsequent improvements in hemodynamics and PA remodeling in animals with PAH through mechanisms that may be experimentally and clinically beneficial.     

Sildenafil improves walk distance in idiopathic pulmonary fibrosis

Pulmonary hypertension is a common finding in patients with idiopathic pulmonary fibrosis (IPF), and is associated with increased morbidity and mortality. Therapy with sildenafil has been shown to decrease pulmonary vascular resistance in patients with pulmonary fibrosis and may improve functional status. Patients with IPF and documented pulmonary hypertension were followed up in an open-label study of sildenafil. The 6-min walk test distance (6MWD) was obtained before and after 3 months of sildenafil therapy. Fourteen patients were followed up in the study; 11 patients completed both 6-min walk tests. The mean improvement in walk distance was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of "responders" (ie, >/= 20% improvement in 6MWD) or "nonresponders" (ie, < 20% change or unable to complete), 57% were classified as responders. Sildenafil is a promising and well-tolerated therapeutic agent for use in patients with IPF and pulmonary hypertension, and should be studied in a large, well-controlled trial.     

Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension

Background:Sleep may be associated with significant respiratory compromise in patients with lung disease and can result in hypoxia. In patients with pulmonary arterial hypertension (PAH), nocturnal desaturation may not be reflected in daytime evaluations of oxygenation and can lead to worsening pulmonary hemodynamics. The study was conducted to determine the prevalence and significance of nocturnal oxygen desaturation in patients with PAH.Methods:A cross-sectional study conducted at the Cleveland Clinic. Patients were followed up at our institution except for the overnight oximetry study done at home. Data regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary function, and functional capacity were collected.Results:Forty-three patients (mean age, 47.9 ± 13.5 years [± SD]; 36 women and 7 men) underwent nocturnal oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated with connective tissue diseases (12%). The majority of patients were New York Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%) spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%. Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002). Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular resistance. On echocardiography, desaturators were more likely to have moderate or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only one patient had significant sleep apnea.Conclusions:Nocturnal hypoxemia is common in PAH patients and correlates with advanced pulmonary hypertension and right ventricular dysfunction. Approximately 60% patients without exertional hypoxia had nocturnal desaturation. Overnight oximetry should be considered in the routine workup of PAH patients who do not demonstrate exertional desaturation.     

Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide

STUDY OBJECTIVES: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH. DESIGN: Single center, case series, pharmacohemodynamic study. SETTING: Cardiac catheterization laboratory of a tertiary care academic teaching hospital. PATIENTS: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH. INTERVENTIONS: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization. MEASUREMENTS AND RESULTS: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 +/- 5%, PVR by 12 +/- 5%, systemic vascular resistance (SVR) by 13 +/- 6%, and pulmonary capillary wedge pressure by 12 +/- 7%, and increased CI by 14 +/- 5% (all p < 0.05) [+/- SEM]. The combination of inhaled NO and sildenafil decreased PVR by 50 +/- 4%, decreased SVR by 24 +/- 3%, and increased CI by 30 +/- 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function. CONCLUSIONS: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH.     

Left ventricular diastolic dysfunction in patients with COPD in the presence and absence of elevated pulmonary arterial pressure

BACKGROUND: Increased right ventricular afterload leads to left ventricular diastolic dysfunction due to ventricular interdependence. Increased right ventricular afterload is frequently present in patients with COPD. The purpose of this study was to determine whether left ventricular diastolic dysfunction could be detected in COPD patients with normal or elevated pulmonary artery pressure (PAP). METHODS: Twenty-two patients with COPD and 22 matched control subjects underwent pulsed Doppler echocardiography. Left ventricular systolic dysfunction and other causes of left ventricular diastolic dysfunction (eg, coronary artery disease) were excluded in all patients and control subjects. PAP was measured invasively in 13 patients with COPD. RESULTS: The maximal atrial filling velocity was increased and the early filling velocity was decreased in patients with COPD compared to control subjects. The early flow velocity peak/late flow velocity peak (E/A) ratio was markedly decreased in patients with COPD compared to control subjects (0.79 +/- 0.035 vs 1.38 +/- 0.069, respectively; p < 0.0001), indicating the presence of left ventricular diastolic dysfunction. The atrial contribution to total left diastolic filling was increased in patients with COPD. This was also observed in COPD patients with normal PAP, as ascertained using a right heart catheter. The atrial contribution to total left diastolic filling was further increased in COPD patients with PAP. PAP correlated with the E/A ratio (r = -0.85; p < 0.0001). CONCLUSIONS: Left ventricular diastolic dysfunction is present in COPD patients with normal PAP and increases with right ventricular afterload.     

Normal bronchial blood flow in COPD is unaffected by inhaled corticosteroids and correlates with exhaled nitric oxide

BACKGROUND: In COPD patients, there is reduced vascularity and inflammation of the bronchi, which may have opposite effects on bronchial blood flow (QAW). We studied the relationship of QAW with the fraction of exhaled nitric oxide (FENO), which is a potent vasodilator. We also investigated the vascular response to budesonide and a beta(2)-agonist. METHODS: We measured QAW in 17 patients with COPD (mean [+/- SEM] age, 67 +/- 3 years; 10 male patients; mean FEV(1), 57 +/- 3% predicted; mean FEV(1)/FVC ratio, 54 +/- 4%), all of whom were ex-smokers, and in 16 age-matched nonsmoking volunteers (mean age, 64 +/- 4 years) and compared this to FENO. QAW was measured using the acetylene dilution method. RESULTS: Mean QAW was similar in patients with COPD (34.29 +/- 1.09 microL/mL/min) compared to healthy subjects (35.50 +/- 1.74 microL/mL/min; p > 0.05) and was not affected by long-term treatment (35.89 +/- 1.63 microL/mL/min) or short-term treatment (32.50 +/- 1.24 microL/mL/min; p < 0.05) with inhaled budesonide. QAW positively correlated with the diffusion of carbon monoxide (ie, carbon monoxide transfer coefficient: r = 0.74; p < 0.05). FENO levels were mildly elevated in steroid-treated patients (10.89 +/- 0.87 parts per billion [ppb]) and untreated patients (9.40 +/- 0.86 ppb) compared to the control group (8.22 +/- 0.57 ppb; p < 0.05) and were correlated with QAW (r = 0.6; p < 0.05). Ten minutes after the inhalation of 200 microg of albuterol, QAW was more elevated in healthy control subjects (59.33 +/- 2.40 microL/mL/min) compared to COPD patients (38.00 +/- 0.58 microL/mL/min; p < 0.05), indicating that COPD patients may have a reduced bronchial vascular reactivity. CONCLUSIONS: QAW is normal in COPD patients and is not affected by therapy with inhaled corticosteroids or beta(2)-agonists. In addition, QAW correlates with levels of FENO, which may have a regulatory role.     

Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines

A consensus panel convened by the American College of Chest Physicians developed guidelines for the treatment of pulmonary arterial hypertension (PAH) that were published in 2004. Subsequently, several important clinical trials have been published, and new treatments have received regulatory approval. In addition, add-on and combination therapy are being explored, which promise to open new therapeutic avenues. This article, taking into consideration studies published prior to September 1, 2006, provides an update to the previously published guidelines. The original guidelines have been summarized, a discussion of new studies has been added, and the treatment algorithm has been revised to take into account recent developments in therapy. This update provides evidence-based treatment recommendations for physicians involved in the care of patients with PAH. Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended.     

A case-control study of obstructive sleep apnea-hypopnea syndrome in obese and nonobese chinese children

BACKGROUND: Obesity is a risk factor for obstructive sleep apnea-hypopnea syndrome (OSAHS) in adults. However, the prevalence of OSAHS in children is not clear, and the relationship between obesity and OSAHS remains controversial. METHODS: Obese children were recruited from the endocrinology, respiratory, and ear, nose, and throat clinics. Weight-matched, age-matched, and sex-matched children were recruited as control subjects. Standard questionnaires were administered, and a standardized physical examination was carried out. Lateral neck roentgenography, sleep polysomnography, full blood count, and arterial blood gas analysis were also performed. Children with body mass index z-scores of > 1.96 were considered to be obese. An adenoidal/nasopharygeal ratio of > 0.67 was considered to constitute adenotonsillar hypertrophy (ATH). OSAHS was defined as an apnea-hypopnea index (AHI) score of > 5 or obstructive apnea index (OAI) score of > 1. RESULTS: Ninety-nine obese children and 99 control subjects were recruited into the study. Obese patients had significantly higher AHI and OAI scores, and lower sleep efficiency and minimum arterial oxygen saturation (MinSao(2)) than control subjects. The prevalence of OSAHS was significantly higher in obese children with or without the ATH groups than their nonobese counterparts (odds ratio, 1.9 vs 108, respectively; 95% confidence interval, 1.21 to 4.7 vs 6.2 to 191, respectively). Obesity, tonsillar hypertrophy, and adenoid hypertrophy were independent risk factors for OSAHS (p < 0.001, p = 0.042, and p = 0.004, respectively). There was a positive correlation between the degree of obesity and AHI (r = 0.535; p < 0.001), and an inverse correlation between obesity and MinSao(2) (r = -0.507; p < 0.001). End-tidal CO(2), Paco(2), and bicarbonate levels were within the normal range. CONCLUSIONS: Obesity is a risk factor for OSAHS, and the degree of obesity is positively correlated with the severity of OSAHS.