Successful management of portopulmonary hypertension with beraprost

Portopulmonary hypertension is a complication of chronic liver disease, which has significant effects on survival and prognosis. Although the pathogenesis of pulmonary arterial hypertension has been well known, portopulmonary hypertension is often underestimated in patients with chronic liver disease. Every clinician who manages patients with chronic liver disease complaining of dyspnea should consider portopulmonary hypertension because this disorder requires special treatment. Herein, a 40-year-old woman with liver cirrhosis who complained of dyspnea on exercise is presented. She was diagnosed with portopulmonary hypertension by echocardiography and right-heart catheterization. Beraprost was used to reduce the pulmonary arterial pressure and improve the symptoms. Her symptoms were improved after 2 weeks, and improved symptoms and reduced pulmonary arterial pressure were sustained for 18 months.     

肺动脉高压的诊断和治疗进展

肺动脉高压是一种病死率很高的严重疾病,它以肺血管阻力不断升高为主要特征并最终引起右心衰竭和死亡。近年来,在肺动脉高压的诊断、治疗的研究中取得了长足的进步。规范的诊断和治疗将有助于改善肺动脉高压患者的生活质量和预后。     

Pulmonary arterial hypertension

Pulmonary arterial hypertension is a progressive disease of pulmonary vasculature characterized by increased mean pulmonary arterial pressure and elevated vascular resistance with normal left-sided pressures, differentiating it from left-sided heart disease. The pathogenesis involves thrombosis, vasoconstriction, and remodeling of small pulmonary arteries. It presents with common symptoms such as shortness of breath, chest pain, and decreased exercise tolerance. Left untreated, progressive increase in right ventricular overload leads to right heart failure and death. Over the course of the past decade, better understanding of the pathogenesis and an increasing number of treatment options have resulted in improved prognosis and quality of life.     

肺动脉高压的治疗进展

肺动脉高压是以肺小动脉的血管痉挛、内膜增生和重构为主要特征的一种疾病。它是一进展性疾病,生存期为2.8年,早期诊断和治疗干预是改善患者预后的重要措施,现将新近的治疗进展综述。     

内皮素受体拮抗剂在肺动脉高压中的应用

肺动脉高压是指静息时肺动脉平均压>25 mm Hg(1 mm Hg=0.133 3 kPa)或者运动时肺动脉平均压≥30 mm Hg。随着肺动脉高压发病机制的研究进展,针对细胞增生和血管重塑的治疗大大改善了肺动脉高压的预后。现就内皮素受体拮抗剂在肺动脉高压中的应用进行综述。     

The pressure-flow response of the pulmonary circulation in patients with heart failure and pulmonary vascular disease

Although it is well known that the pulmonary circulation is altered in patients with pulmonary arterial or venous hypertension, the resultant hemodynamic behavior has not been systematically studied. We undertook to do so in a group of patients with pulmonary hypertension of diverse etiology. We measured pulmonary arterial (PAP) and occlusive wedge pressures and cardiac output at rest (i.e., standing) and during progressive upright treadmill exercise in 51 patients. Forty-two had chronic, stable, cardiac failure secondary to ischemic, myopathic or valvular heart disease and were grouped according to whether their mean PAP was less than (normotensive) or greater than (hypertensive) 19 mm Hg, and nine had pulmonary vascular disease of diverse etiology and were considered separately. In the majority of patients, we found that irrespective of whether the hypertension was arterial or venous in origin or etiology: the mean PAP-flow relationship was linear; pulmonary capillary wedge pressure was greater than or equal to the average closure pressure of the pulmonary vascular bed and could therefore be used as the downstream pressure in calculating pulmonary vascular resistance; and pulmonary vascular resistance declined with exercise. Notable exceptions to the third observation were patients with valvular heart disease or a resting pulmonary vascular resistance greater than 800 dyne-sec-cm-5.     

Pulmonale Hypertonie bei chronischen Lungenerkrankungen

Pulmonary hypertension is a well-known complication of chronic respiratory diseases with an adverse influence on prognosis. While hypoxaemia has been traditionally viewed as the main cause of pulmonary vasoconstriction with a subsequent increase of pulmonary arterial pressure, the importance of pulmonary vasculature remodelling is being increasingly realized. Patients with chronic lung diseases who are suspected of having pulmonary hypertension should be screened by transthoracic echocardiography. A diagnosis of pulmonary hypertension should be verified by right heart catheterization, before a specific therapy is started. Patients newly diagnosed with pulmonary hypertension should undergo spirometry, body plethysmography, arterial blood gas analysis at rest and during exercise as well as a pulmonary CT scan with regard to an underlying disease of the respiratory system. Sleep-related disorders of breathing should be excluded by polysomnography. Long-term oxygen treatment in order to maintain sufficient oxygenation is the key therapy in patients with parenchymal lung disease and pulmonary hypertension. Given the lack of evidence of a beneficial effect, pulmonary vasodilators cannot be recommended for these patients.     

肺动脉高压治疗进展

肺动脉高压是一种进行性发展且预后不良的疾病.随着对肺动脉高压发病机制研究的不断深入,其治疗已从单纯的血管扩张剂治疗发展到以疾病的分子遗传基础为靶向的药物治疗.本文着重介绍有关肺动脉高压治疗方面的进展.     

Bosentan improves exercise tolerance and Tei index in patients with pulmonary hypertension and prostanoid therapy

STUDY OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease with a bad prognosis. Prostanoids are well established in the medical treatment of this disease. Treatment of patients with progressive disease despite prostanoids remains a therapeutic challenge. In this study, we examined the effect of adding bosentan, an endothelin antagonist, to existing prostanoid therapy on exercise capacity (6-min walking distance [6MWD]) and right ventricular (RV) function (Tei index) in patients with progressive pulmonary hypertension. DESIGN: Prospective, nonrandomized, open-label study. SETTING: University hospital. PATIENTS: Sixteen patients with pulmonary hypertension (PAH, n = 10; pulmonary hypertension due to other cause, n = 6) with progressive disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or iloprost IV (n = 3). INTERVENTIONS: Combination therapy with bosentan (final dosage, 125 mg bid) was initiated following an interval of 3-months minimum of unchanged prostanoid therapy. MEASUREMENTS AND RESULTS: Tei index, 6MWD, and New York Heart Association (NYHA) functional class were assessed prior to the initiation of combination therapy (baseline), at 6 months after initiation of combination therapy, and every 3 months thereafter. Two patients were followed up for 6 months only; all remaining patients reached a mean follow-up period (+/- SD) of 13.5 +/- 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 +/- 66 m at 6 months and 44.6 +/- 66 m at the last follow-up (both time points vs baseline, p < 0.001), and Tei index improved by -0.13 +/- 0.08 at 6 months and - 0.13 +/- 0.11 at the last follow-up (both time points vs baseline, p < 0.001). All patients reported subjective improvements. Nine of 16 patients exhibited improvement in NYHA functional class at 6 months. No side effects occurred that required dose adjustment or discontinuation of the study medication. CONCLUSION: Bosentan administered to patients with progressive pulmonary hypertension receiving prostanoids resulted in an increased exercise capacity and an improved RV function. Bosentan therefore appears to be well suited for combination therapy with prostanoids in selected patients pending results of ongoing randomized trials.     

Pulmonary arterial hypertension

Pulmonary arterial hypertension is a chronic disorder of the pulmonary circulation characterized by an increased pulmonary artery pressure and an impaired cardiac function. It can present as idiopathic form or associated with several systemic diseases. Typical symptoms include progressive dyspnoea and exercise intolerance. When pulmonary arterial hypertension is suspected, echocardiography is the key investigation for noninvasive assessment of the disease. The diagnosis requires an invasive measurement of pulmonary hemodynamics by right heart catheterization. Treatment is based on general measures and application of pulmonary vasoactive compounds, such as prostanoids, endothelin receptor blockers and phosphodiesterase 5 inhibitors. These treatment options can be combined at progression of the disease. Lung transplantation might be an option in patients refractory to medical therapy.     

Relationship between exercise desaturation and pulmonary haemodynamics in COPD patients.

Pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD) has traditionally been explained as an effect of hypoxaemia. Recently, other mechanisms, such as arterial remodelling caused by inflammation, have been suggested. The aim of this study was to investigate whether exercise-induced PH (EIPH) could occur without concurrent hypoxaemia, and whether exercise-induced hypoxaemia (EIH) was regularly accompanied by increased pulmonary artery pressure or pulmonary vascular resistance index (PVRI). Pulmonary haemodynamics in 17 patients with COPD of varying severity, but with no or mild hypoxaemia at rest, were examined during exercise equivalent to the activities of daily living (ADL) and exhaustion. EIPH occurred in 65% of the patients during ADL exercise. Pulmonary arterial pressure during exercise was negatively correlated with arterial oxygen tension, but EIPH was not invariably accompanied by hypoxaemia. Conversely, EIPH was not found in all patients with EIH. The resting PVRI was negatively correlated with arterial oxygen tension during ADL exercise, but an elevated PVRI without EIH occurred in 35% of the patients. In conclusion, exercise-induced pulmonary hypertension occurred during exercise equivalent to the activities of daily living in chronic obstructive pulmonary disease patients with no or mild hypoxaemia at rest. Although pulmonary artery pressure and arterial oxygen tension were negatively correlated during exercise, a consistent relationship between hypoxaemia and pulmonary hypertension could not be demonstrated. This may indicate that mechanisms other than hypoxaemia contribute significantly in the development of pulmonary hypertension in these patients.     

Pulmonalarterielle Hypertonie

Pulmonary arterial hypertension is a chronic disorder of the pulmonary circulation characterized by an increased pulmonary artery pressure and an impaired cardiac function. It can present as idiopathic form or associated with several systemic diseases. Typical symptoms include progressive dyspnoea and exercise intolerance. When pulmonary arterial hypertension is suspected, echocardiography is the key investigation for noninvasive assessment of the disease. The diagnosis requires an invasive measurement of pulmonary hemodynamics by right heart catheterization. Treatment is based on general measures and application of pulmonary vasoactive compounds, such as prostanoids, endothelin receptor blockers and phosphodiesterase 5 inhibitors. These treatment options can be combined at progression of the disease. Lung transplantation might be an option in patients refractory to medical therapy.     

Exercise testing and training in chronic lung disease and pulmonary arterial hypertension

Research examining the clinical value of exercise testing and training in patients with chronic lung disease and pulmonary arterial hypertension (PAH) is less robust compared with cardiac populations but nevertheless highly supportive. Functional limitations are common in these patients, and exercise testing provides important information pertaining to the degree of this limitation, disease severity, and prognosis. Moreover, exercise testing, particularly in conjunction with ventilatory expired gas analysis, serves as a valuable diagnostic tool when the mechanism of the functional limitation and abnormal exertional symptoms is uncertain. Most work with respect to the benefits of exercise training has been performed in chronic obstructive lung disease cohorts and is used to support pulmonary rehabilitation. Emerging data indicate that exercise training is likewise beneficial in patients with interstitial lung disease and PAH. This review summarizes the evidence supporting the value of exercise testing and training and provides recommendations for clinical practice.     

Pulmonary arterial hypertension: the key role of echocardiography

Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.     

Pulmonary arterial hypertension in children

Pulmonary arterial hypertension is a serious progressive condition with a poor prognosis if not identified and treated early. Because the symptoms are nonspecific and the physical findings can be subtle, the disease is often diagnosed in its later stages. Remarkable progress has been made in the field of pulmonary arterial hypertension over the past several decades. The pathology is now better defined, and significant advances have occurred in understanding the pathobiologic mechanisms. Risk factors have been identified, and the genetics have been characterized. Advances in technology allow earlier diagnosis as well as better assessment of disease severity. Therapeutic modalities such as new drugs, e.g., epoprostenol, treprostinil, and bosentan, and surgical/interventional options, e.g., transplantation and atrial septostomy, which were unavailable several decades ago, have had a significant impact on prognosis and outcome. Thus, despite our inability to cure pulmonary arterial hypertension, advances in medical treatments over the past two decades have resulted in significant improvement in outcomes for children with various forms of pulmonary arterial hypertension. This report is a review the current state of the art for pulmonary arterial hypertension in 2004, with an emphasis on childhood pulmonary arterial hypertension and specific recommendations for current practice and future directions.     

Pulmonale Hypertonie

Pulmonary hypertension has dramatically evolved as a new scientific field triggered by the development of targeted pulmonary arterial hypertension (PAH) therapies. Pulmonary hypertension is defined by elevated resting pulmonary arterial pressures but the definition of normal values during exercise is currently not possible. Diagnostic tools include the history, physical examination, electrocardiography (ECG), thoracic X-ray and echocardiography. In scleroderma patients a reduced diffusing capacity of the lungs for carbon monoxide (DLCO) is a marker of PAH. Approved PAH therapies include three prostanoids, two endothelin receptor antagonists and two phosphodiesterase 5 inhibitors. These therapies have substantially improved the prognosis of PAH patients. A novel soluble guanylate cyclase (sGC) stimulator has been submitted for approval. There are increasing numbers of elderly PAH patients who have an adverse prognosis as compared with classical PAH patients. In particular those with simple or combined heart and lung diseases pose a challenge for the future.     

Changing the prognosis of pulmonary arterial hypertension: impact of medical therapy

Pulmonary arterial hypertension (PAH) is a progressive arteriopathy of the pulmonary circulation that can affect a wide group of patients. Presentation and natural history of PAH are intimately linked to progressive right ventricular failure. Historically, survival in PAH has been poor, especially for patients with PAH associated with progressive systemic sclerosis and human immunodeficiency virus. Oral, subcutaneous, and intravenous therapies that have emerged during the last decade can improve symptoms and hemodynamics. This review explores the impact of these therapies on prognosis in PAH, which ultimately rests on the ability to reverse the pulmonary arteriopathy and preserve right ventricular function.     

Pulmonary hypertension in chronic obstructive pulmonary disease. Multivariate analysis

The severity of pulmonary hypertension was evaluated by right cardiac catheterization in 89 patients with stable chronic obstructive pulmonary disease, both at rest and during maximum treadmill exercise. Thirty-one patients were found to have pulmonary hypertension at rest, defined as a mean pulmonary arterial pressure of 20 mm Hg or more. Although the remaining 58 patients had normal mean pulmonary arterial pressure at rest, three developed pulmonary hypertension during exercise (mean pulmonary arterial pressure greater than or equal to 35 mm Hg). Multiple anthropometric, spirometric, radiographic, and gas-exchange variables were analyzed and correlated with the hemodynamic data to define their value in predicting mean pulmonary arterial pressure. While arterial oxygen pressure (PaO2) at maximum exercise was the variable most highly correlated with resting mean pulmonary arterial pressure (r = -0.67), stepwise multiple linear regression analysis indicated that measurement of the diameter of the right descending pulmonary artery and arterial carbon dioxide tension (PaCO2) also contributed to the prediction of mean pulmonary arterial pressure. Spirometric indices of airflow obstruction, hyperinflation, and the diffusing capacity of the lung for carbon monoxide correlated poorly with the severity of pulmonary hypertension and consequently were not useful predictors of mean pulmonary arterial pressure. The threshold criteria of a PaO2 less than 60 mm Hg or a PaCO2 more than 40 mm Hg were reasonably accurate for a diagnosis of pulmonary hypertension. These arterial blood gas criteria were superior to the spirometric and radiographic variables examined in predicting pulmonary hypertension prior to the development of clinically overt cor pulmonale.     

Tadalafil improves quality of life and exercise tolerance in idiopathic pulmonary arterial hypertension

Pulmonary arterial hypertension has a poor prognosis quoad vitam et valitudinem. Herein, we report on a middle-aged woman affected by idiopathic pulmonary arterial hypertension whose quality of life and exercise tolerance improved remarkably after a six-month course of treatment with the long-acting phosphodiesterase-5 inhibitor tadalafil.     

Double mitral valve orifice in atrioventricular defects.

Pulmonary vascular resistance normally falls or remains unchanged during exercise. Seven children with pulmonary hypertension were exercised during cardiac catheterisation after operative correction of ventricular septal defect (6) and truncus arteriosus (1). Except for the presence of moderate pulmonary hypertension, resting haemodynamics in these seven children were similar to those of normal children of equal age, but during exercise the postoperative patients showed a rise rather than a fall (+2% vs -18%) in total pulmonary vascular resistance. Two of the seven children had a substantial increase in pulmonary arteriolar resistance during exercise (from 509 to 715 dyne s cm-5 in one patient and from 606 to 828 dyne s cm-5 in the other). These two patients did not differ from normal children in respect of arterial or mixed venous oxygen saturations or of pH with exercise, nor was left atrial pressure related to the rise in pulmonary resistance. These two patients, however, had only a small rise in cardiac output during exercise (6.8% and 43.1%) in spite of a substantial increase in oxygen consumption (121% and 373%). One of the patients with exercise-induced pulmonary vasoconstriction had an 82% increase in resting pulmonary vascular resistance over a five year period subsequent to her first exercise study. Analysis of these data, and those previously reported, suggests that exercise induced pulmonary vasoconstriction may occur in 10 to 25% of patients who survive correction of certain congenital cardiac defects. The vasoconstriction cannot be attributed to abnormal changes in blood gases or left atrial pressure, and may be an early sign of progressive pulmonary hypertension.