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Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratification, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorporation of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediatehigh risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.

Premature closure of the foramen ovale (FO) or intrauterine restrictive FO is a rare entity of unknown etiology. This pathology is associated with an elevated risk of pulmonary hypertension, which can cause congestive heart failure with hydrops and fetal death. Patients with restrictive intrauterine FO may develop left ventricle diastolic dysfunction and pulmonary edema. A newborn with increased right cavities in the prenatal ultrasound is presented. In postnatal echocardiogram, dilatation of right cavities was confirmed with pulmonary hypertension in the systemic range and immobile interatrial septum with closed FO. After 9 days of persistent respiratory distress, an echocardiogram was performed with improvement of pulmonary hypertension but with mild biventricular and diastolic and systolic dysfunction of the left ventricle with pulmonary edema. Diuretic treatment was decided, with normalization of ventricular function., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Pulmonary hypertension is a common complication of bronchopulmonary dysplasia, with a high mortality rate. Despite the high incidence of pulmonary hypertension, there are few available treatments. Epoprostenol and treprostinil are prostaglandin I2 analogs that activate adenylate cyclase and increase cyclic adenosine monophosphate in the pulmonary arterial smooth muscle cells. Therefore, they may be an effective treatment for these patients. We report the use of prostaglandin I2 analogs in an extremely low birth weight preterm baby with severe bronchopulmonary dysplasia associated with pulmonary hypertension non-responding to inhaled nitric oxide and sildenafil. In our patient this treatment resulted in remarkable clinical and echocardiographic improvement, evident after a few weeks of treatment., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition., Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia., Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot., Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway., Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

Pulmonary hypertension associated with human immunodeficiency virus infection is an extremely rare disease in pediatrics; it requires a high clinical suspicion to reach a diagnosis. Its appearance poses an unfavorable prognostic, but early diagnosis and specific treatment can improve outcomes. We report the clinical case of a fifteen-year-old patient diagnosed with human immunodeficiency virus infection of vertical transmission, without antiretroviral treatment, with cough and progressive exertional dyspnea, associated with signs of right heart failure in which severe pulmonary hypertension was diagnosed. After discarding other causes, it was assumed pulmonary hypertension associated with human immunodeficiency virus infection. Treatment was performed with sildenafil with good response., (Sociedad Argentina de Pediatría.)

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy., Aim: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile., Patients and Methods: One hundred fifteen patients aged 43 ± 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 ± 14 mmHg and their six minutes walking capacity was 368 ± 119 m. They were followed for 58 ± 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH., Results: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival., Conclusions: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature.

In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively., (Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future., (Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Sarcoidosis is a pleomorphic disease that can present with pulmonary hypertension (PH). What little information is available about the association of these two diseases comes mainly from small series of patients scheduled for transplant. We present 4 cases of mild pulmonary involvement in whom right catheterisation was performed and PH-specific therapy was administered. After obtaining written consent, a genetic study was performed that showed mutations in PH-related genes in 3 of the patients. This is the first study of its kind to yield genetic information for this type of PH., (Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.)

Inhaled iloprost is one of the most recent drugs from prostanoids group's in the treatment of pulmonary arterial hypertension. His place in pulmonary hypertension seen in the perioperative cardiovascular surgery has not been defined. In this review we analyze pulmonary hypertension group's susceptibles of cardiac surgery and its importance, besides the current clinical evidence from drug use in this context., (Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Pulmonary hypertension (PHT) and the resulting right ventricle dysfunction are important risk factors in patients who undergo cardiac surgery. The treatment of PHT and right ventricle dysfunction should be focused on maintaining the correct right ventricle after load, improving right ventricle function and reducing the right ventricle pre-load and therefore reducing pulmonary vascular resistance by means of vasodilators. A combined therapy of vasodilators and medicines which have different mechanisms of action, is becoming an option for the treatment of PHT. We present a 65 year old woman that suffered from mitral regurgitation, aortic valve disease, tricuspid and ascending aortic dilation with 115mmHg of pulmonary artery pressure (by ultrasound evaluation). The patient was operated on of mitral, aortic valve and tricuspid plastia and proximal aortic artery plastia as well. Previosly to surgery the patient suffered right ventricle dysfunction and PHT and was treated with nitric oxide, intravenous sildenafil and levosimendan. Subsequent evolution was satisfactory, PHT being controlled, without arterial hypotension nor respiratory alterations., (Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use., (Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Objective: To evaluate the efficiency of initiation with endothelin receptor antagonists, ambrisentan or bosentan, followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids in the treatment of pulmonary arterial hypertension, from the Spanish National Health System perspective., Methods: A Markov model was developed based on the four New York Heart Association functional classes. A panel of three experts reached a consensus on patient management based on clinical practice. Patients revised their treatment every 12 weeks, based on their health status and previous medication records. Pharmacological treatment costs and costs associated with very frequent adverse events (AE) were considered in a horizon of 60 weeks. Outcomes were measured in qualityadjusted life years (QALY). A probabilistic sensitivity analysis was performed., Results: No clinically relevant differences in QALY per-patient and year were found for initiation with ambrisentan and bosentan: 0.6853 and 0.6902, respectively. Initiation with ambrisentan resulted in lower pharmacological treatment and AE management costs: ?35,550 and ?117 versus ?40,224 and ?171. In the sensitivity analysis, initiation with ambrisentan resulted in a negative significant cost difference: ?-4,982; CI95%[?- 8,014; ?-2,500]; while no significant differences in QALY were found: -0.0044; CI95%[-0.0189; 0.0101]., Conclusions: Initiation with ambrisentan followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids yields comparable outcomes at lower costs than initiation with bosentan., (Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.)

The increase in survival that has been achieved with the new treatments in the era of highly active antiretroviral therapy, has enabled clinicians and researchers to analyze issues that emerge in the long term in patients with HIV infection. Although the majority of cardiovascular complications have been widely described, the pathogenesis of pulmonary arterial hypertension is still poorly understood, and is one of the more complex and feared complications as it worsens the prognosis and quality of life of these patients This article reviews newer aspects related to the aetiology, symptoms, diagnosis and treatment of this disease., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Introduction: An excessive risk for bacteremia has recently been reported in patients with pulmonary arterial hypertension (PAH) treated with intravenous treprostinil. We aimed to assess this association in a cohort of patients from a Spanish referral center., Patients and Methods: We performed a retrospective cohort study that included 55 patients diagnosed with PAH who received a continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil) for ≥1month at our center between January 1991 and December 2011. The risk factors associated with the incidence of bacteremia were analyzed with the log-rank test., Results: After a total follow-up of 64,453 treatment days, we found 12 episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram-negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118 episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938 episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037). All episodes of bacteremia due to Gram-negative bacilli were diagnosed in patients on treprostinil. In the univariate analysis the treatment with intravenous treprostinil was associated with the incidence of bacteremia (hazard ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of events prevented us from performing a multivariate analysis., Conclusions: Therapy with intravenous treprostinil is associated with a higher risk for bacteremia, especially due to non-fermenting Gram-negative bacilli. This association should be taken in consideration when choosing empirical antibiotic therapy for patients with PAH and sepsis., (Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.)

Pertussis is a contagious disease that may develop a serious clinical picture by hypoxemia and pulmonary hypertension refractory to treatment. The syndrome of hyperviscosity and arteriolar thrombosis is responsible for the cardiocirculatory collapse. Our objective is to describe the evolution of a series of patients with severe pertussis, some of whom received exchange transfusion (ET) as an alternative treatment. We analyzed 41 patients' clinical charts with diagnosis of pertussis treated in the Pediatric Intensive Care Units during the 2003-2011 period. The mean age was 2.38 months. In the 90.2% of cases, the cause of admission to PICU was respiratory failure; 75% required mechanical respiratory support and 39% developed pulmonary hypertension. The overall mortality was 41.4%. Nine patients were treated by ET, 5 died. Conclusion. Severe pertussis is associated with high mortality. ET reduced the mass of circulating leukocytes in 53.5%; ET could be an alternative to conventional treatment, although controlled studies are required to assert it.

The introduction of highly active antiretroviral therapy (HAART) has resulted in a reduction of opportunistic infections associated with cellular and humoral immunosuppression. However, what is still unclear is the impact of HAART on the development of other diseases not associated with AIDS, such as lung cancer and COPD. The aim of this paper is to review the most innovative and relevant aspects of lung pathology in patients infected with HIV., (Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objectives: There is a high incidence of pulmonary hypertension during the lung transplant peri-operative period, and could lead to a haemodynamic deterioration that may require the need of extracorporeal circulation. Our aim was to study the haemodynamic effects on the pulmonary and systemic circulation of the combination of inhaled nitric oxide and iloprost and oral sildenafil in patients with severe pulmonary hypertension during lung transplant surgery., Patients and Methods: Seventeen patients received 10μg of nebulised iloprost during the peri-operative period of the lung transplant when their mean pulmonary pressure exceeded 50mmHg. AU the patients received 50mg of oral sildenafil 30min before anaesthetic induction, 20ppm of inhaled nitric oxide after tracheal intubation. The haemodynamic and respiratory variables were recorded at baseline (after anaesthetic induction), prior to the administering of iloprost, and at 5 and 30min after it was given., Results: The administering of iloprost significantly reduced the pulmonary arterial pressure and significantly increases the cardiac Índex and the right ventrícular ejection fractíon. There were no signíficant changes occurred in the systemic arterial pressure., Conclusions: The triple combination significantly reduces the pulmonary pressures in the lung transplant peri-operative and should be considered when there is severe pulmonary hypertension during the surgery or during the immediate post-operative period of lung transplantation., (Copyright © 2010 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España.. All rights reserved.)

Introduction and Objectives: Bosentan has proven efficacy in pulmonary hypertension in the short term. Little is known about its effects beyond 2 to 3 years. Our objective was to analyze the efficacy and safety of bosentan in the long term (5 years) in patients treated in our center., Methods: This retrospective study sequentially analyzed clinical, functional, and laboratory parameters in a series of patients treated initially with bosentan as monotherapy from 2002 to 2009 in a single hospital. Treatment success was defined as survival without clinical worsening that required additional pulmonary vasodilators., Results: We included 20 patients (70% women, mean age 46 ± 14 years, 65% congenital heart disease), with a median follow-up of 64 months. One patient required withdrawal of bosentan due to adverse effects. At 4 months, significant improvements were achieved in hemodynamic, clinical and functional parameters. Clinical and functional benefits persisted at 5-year follow-up. Overall 5-year survival after beginning bosentan therapy was 95% (84%-100%). Treatment success at 1, 2, 3, 4 and 5 years was 95% (84%-100%), 83% (65%-100%), 78% (58%-98%), 61% (38%-84%), and 41% (16%-66%), respectively. The group with better outcomes had NT-proBNP levels at 1 year <400 pg/mL (P=.013)., Conclusions: In our series, treatment success with bosentan in monotherapy was maintained in 78% at 3-year follow-up and 41% at 5-year follow-up. The group with long-term success showed significantly lower NT-proBNP levels at 1-year follow-up. Survival at 5 years in our series was 95%., (Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

A 33-year-old male with severe hereditary pulmonary arterial hypertension had a confirmed diagnosis of occlusive venopathy and microvasculopathy. He remained stable for three and a half years on oral sildenafil, 75 mg t.i.d. (six-minute walked distance of 375 m vs 105 m at baseline), but required addition of bosentan (125 mg b.i.d.), subsequently. Despite the fatal outcome at five years post-diagnosis, the observations suggest a potential usefulness of vasodilators as a bridge for lung transplant in selected cases with significant venous/capillary involvement. The occurrence of veno-occlusive and capillary lesions in the familial form of pulmonary arterial hypertension reinforces the difficulties with the current classification of the disease.

Background: Pulmonary artery hypertension (PAH) is a progressive disease with high mortality. Major advances had been made in the treatment of this condition during the last decade., Aim: To characterize the clinical evolution and mortality of a cohort of Chilean patients., Material and Methods: Seventeen patients with PAH diagnosed in the last 10 years in two Chilean hospitals were enrolled. Measurements at diagnosis included hemodynamic variables and 6-minute walk test. The patients were followed clinically for 3 years and the observed mortality was compared with that predicted by the prognostic equation proposed by the historic registry of the National Institutes of Health (NIH)., Results: The mean age of patients was 45 years and 80% had an idiopathic PAH. The mean median pulmonary artery pressure was 57 ± 15 mmHg, the cardiac index was 2.4 ± 0.7 l/min/m² and the right atrial pressure was 12 ± 8 mmHg. The 6-minute walk distance was 348 ± 98 m. All patients received anticoagulants. Eighty two percent received ambrisentan, 12% received bosentan, 29% received iloprost and 24% sildenafil. At the end of follow-up only 3 patients had died, with an observed survival rate of 88, 82 and 82% at 1, 2 and 3 years, respectively. In contrast, the survival calculated according to the predictive formula of the NIH was 67, 56 and 45%, respectively. Among surviving patients, an improvement in exercise capacity was observed after one year (p < 0.05)., Conclusions: The observed survival rate was significantly better than that estimated according to historical data. Furthermore, therapy was associated with an improvement in functional capacity after one year. This prognostic improvement is consistent with data of other contemporary registries published after the NIH Registry.

Tadalafil, which was commercialized in 2009, is a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, and may be a safe and effective therapeutic alternative for patients with class II and III pulmonary hypertension (PH) in the World Health Organization's classification--as stated in the Clinical Practice Guidelines for the Diagnosis and Treatment of PH of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)--providing benefits in exercise tolerance, delaying clinical deterioration and improving quality of life. Given the greater half-life of this drug, allowing a single oral dose of 40 mg per day, tadalafil could improve therapeutic compliance--thus facilitating treatment adherence--among patients with PH., (Copyright © 2011 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.)

Pulmonary artery hypertension (PAH) is a category of pulmonary hypertension consisting of mean pulmonary artery pressure greater than 25 mmHg at rest, with normal pulmonary capillary occlusion pressure (less than 15 mmHg) and pulmonary vascular resistance greater than 3 Wood units. The diagnosis of PAH is made through the exclusion of other disorders, including pulmonary, thromboembolic, left ventricular and valvular heart disease. All patients with PAH suspected on the basis of non-invasive tests should undergo right-sided catheterization before treatment is started, with measurement of pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance. Pulmonary vasoreactivity and cardiac output should also be measured. To test pulmonary vasoreactivity, inhaled nitric oxide and intravenous adenosine or epoprosterenol are used. A reduction of 10 mmHg in mean pulmonary arterial pressure or achieving a mean pulmonary artery pressure of less than 40 mmHg, with no change or an increase in cardiac output, is considered a positive response. These criteria are met by only 10% of patients with PAH undergoing this test. Patients with a positive response will probably also show a sustained response to calcium channel blockers. This test should not be used in patients with PAH secondary to left cardiac disease, pulmonary disease or pulmonary embolism., (Copyright © 2011 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.)

Roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-n-(3,5-dichloropyrid-4-yl)benzamide) was the first agent of a novel pharmacological class, selective phosphodiesterase 4 (PDE(4)) inhibitors, approved for the use of chronic obstructive pulmonary disease (COPD). The molecular mechanism of action of roflumilast is inhibition of the PDE(4) isoenzyme with a consequent increase of cyclic adenosine monophosphate. Roflumilast evidently has several pharmacological effects: antiinflammatory, anti-emphysema, and antibiotic actions. This drug also inhibits pulmonary hypertension and reduces mucus hypersecretion. The pharmacological actions leading to these effects are: a) inhibition of reactive oxygen species formation in epithelial cells, neutrophils and smooth muscle cells; b) inhibition of smooth muscle cell proliferation in the pulmonary artery, endothelial cells and probably some inflammatory cells causing pulmonary vascular remodeling; c) inhibition of fibroblasts, with a consequent reduction in pulmonary remodeling and, finally, d) inhibition of mucus production and improved ciliary beat frequency. In summary, roflumilast is the first non-steroidal anti-inflammatory drug that can be used in the treatment of COPD., (Copyright © 2010 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.)

Pulmonary hypertension due to left heart disease is a pathophysiological and hemodynamic state which is present in a wide range of clinical conditions that affect left heart structures. Although the pulmonary circulation has traditionally received little attention, it is reasonable to say that today it is a fundamental part of cardiological evaluation. In patients with heart failure, the most important clinical factors are the presence of pulmonary hypertension and right ventricular function. These factors are also essential for determining prognosis and must be taken into account when making some of the most important therapeutic decisions. The pathophysiological process starts passively but later transforms into a reactive process. This latter process, in turn, has one component that can be reversed with vasodilators and another component that is fixed, in which the underlying mechanism is congestive vasculopathy (i.e. essentially medial hypertrophy and pulmonary arterial intimal fibrosis). Currently no specific therapy is available for this type of pulmonary hypertension and treatment is the same as for heart failure itself. The drugs that have been shown to be effective in pulmonary arterial hypertension have generally had a neutral effect in clinical trials. Nevertheless, we are involved in the clinical development of a number of groups of pharmacological compounds that will enable us to make progress in the near future.

Background: Pulmonary hypertension is a serious disease that, in its terminal phase, requires lung transplantation., Patients and Methods: A retrospective study was undertaken of 15 patients with pulmonary hypertension who underwent lung transplantation between 1994 and 2004. Clinical data recorded before the procedure and during follow-up were reviewed., Results: Pulmonary hypertension was reported as idiopathic in 8 patients (53%) and related to consumption of toxic oil in 2. The remaining causes were documented as chronic peripheral pulmonary embolism, histiocytosis X, venoocclusive disease, scleroderma, and simple corrected congenital heart defect in 1 patient each. The mean values of the hemodynamic variables were 100, 50, and 67 mm Hg for systolic, diastolic, and mean pulmonary artery pressure, respectively; 2.63 L/min for cardiac output; and 20.9 Wood units for total pulmonary resistance. The mean time between diagnosis of pulmonary hypertension and lung transplantation was 5.9 years (range, 0.4-20 y). Seven patients were in functional class III and 8 in functional class IV. The mean 6-minute walk distance was 204 m (range, 0-360 m). Four patients (26%) died during the during the perioperative period and 9 (60%), 7 (46%), and 6 (40%) were still alive at 1, 3, and 5 years, respectively., Conclusions: Double-lung transplantation is a therapeutic option that, in certain cases, has similar outcomes to those achieved with the most aggressive medical treatment for pulmonary hypertension.

Chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure. Individuals with COPD have a 4.5-fold greater risk of developing heart failure than those without. The sensitivity and specificity of clinical judgment in the diagnosis of heart failure in patients with COPD can be enhanced by biological markers such as B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide. Correct interpretation of imaging results (mainly echocardiographic findings) and lung function tests can also help establish the co-occurrence of both conditions. There is little evidence on the management of patients with COPD and heart failure, although treatment of COPD undeniably affects the clinical course of patients with heart failure and viceversa.

Pulmonary thromboendarterectomy is the treatment of choice in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, specific medical treatment of pulmonary hypertension (PH) can be an alternative or play a complementary role to surgery. Thus, in patients unsuitable for surgery due to distal thrombotic obstruction, residual or persistent PH after surgery or very severe PH and a high-risk hemodynamic profile, medical treatment may improve their clinical course and the outcome of thromboendarterectomy. Patients with distal obstruction in the pulmonary tree and those with residual PH after surgery show clinical and hemodynamic deterioration due to progression of the pulmonary vascular disease in the smallcaliber arterioles. Conventional treatment with diuretics, anticoagulants and oxygen therapy has been demonstrated to have little effectiveness. In the last decade, numerous drugs have been developed for the treatment of PH: prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors acting principally in vascular remodelling of small-caliber arterioles. Although evidence of the effectiveness of these drugs in PH and the histological similarity of small-vessel vasculopathy in CTEPH to that of other forms of PH provide the main rationale for the use of these drugs in patients with CTEPH, the evidence from clinical trials is still limited., (Copyright 2009 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.)

Background: Pulmonary hypertension (PH) is a factor of poor prognosis in the postoperative period of heart transplant (HT) and thus, the study of the degree of reversibility to vasodilators is mandatory during the preoperative assessment., Objective: To evaluate the pulmonary and systemic hemodynamic effects of sildenafil as a vasodilator during the PH reversibility test in patients that are candidates to HT., Methods: Patients awaiting HT were submitted to the measurement of systemic and pulmonary hemodynamic variables before and after the administration of a single sublingual dose of 100 mg of sildenafil during right heart catheterization., Results: Fourteen patients (age: 47+/-12 years, 71.4% men) with advanced heart failure Ejection Fraction (EF) 25 +/- 7%, Functional Class (FC - NYHA) FC III - 6 and FC IV - 8, were evaluated in this study. The acute administration of sildenafil showed to be effective in decreasing the systolic (62.4 +/- 12.1 vs 51.5 +/- 9.6 mmHg, CI=95%, p<0.05) and mean (40.7 +/- 7.3 vs 33.8 +/- 7.6 mmHg, CI=95%, p <0.05) pressures of the pulmonary artery. There was also a significant decrease in the pulmonary (4.2 +/- 3 vs 2.0 +/- 0.9 uWood, CI=95%, p<0.05) and systemic vascular resistance (22.9 +/- 6.8 vs 18.6 +/- 4.1 Wood, CI=95%, p<0.05), associated to an increase in the cardiac output (3.28 +/- 0.79 vs 4.12 +/-1.12 uWood, CI=95%, p<0.05) without, however, significantly interfering in the systemic arterial pressure (87.8 +/- 8.2 vs 83.6 +/- 9.1 mmHg, CI=95%, p=0.3)., Conclusion: The sublingual administration of sildenafil is an effective and safe alternative as a vasodilator during the PH reversibility test in patients with heart failure and awaiting a HT.

There have been spectacular developments in pulmonary arterial hypertension (PAH), both in its treatment and knowledge of its pathogenesis. Several studies have been published throughout 2008 that have contributed to improve these two aspects a little. As regards the pathogenesis, mutations in BMPR2 continue gaining points as fundamental factors in the development of the disease. It has been shown that patients who carry any of them have a more rapid and severe clinical course. There is a relationship between the BMPR2 pathway and inflammation of the pulmonary vascular tree. A new anti-endothelin drug, ambrisentan, has also appeared on the scene this year. With an efficacy comparable to other drugs of its group, the secondary effects appear to be a lot less. An important work has been the demonstration of an improvement in several parameters in functional class II in patients with PAH with bosentan. Results using new combinations, such as sildenafil and epoprostenol, have also been presented. A common type of PAH is that which seems to be associated with thromboembolic disease. Treatment with sildenafil and in some selected cases, percutaneous angioplasty, has obtained favourable responses. Finally, in 2008, two new consensus documents have emerged, one Spanish and the other British, which in the light of current knowledge, give a clearer insight into the management of this serious disease.

Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.

Pulmonary arterial hypertension is an idiopathic process or can be associated with another circumstances (connective tissue diseases, congenital heart disease, portal hypertension, exposure to appetite suppressants or another drugs or infectious agents such as HIV). Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed incidentally or during screening of asymptomatic populations at risk. We reviews systematic screening for the approach to diagnosing pulmonary arterial hypertension. A diagnostic algorithm can guide the evaluation but it can be modified according to specific clinical circumstances. The number of therapeutic options has increased.in the last years. We reviews the use of calcium-channel blockers, prostacyclin (and analogues), endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, and the use of combination therapy, and provides specific recommendations about the actual treatment.

Until recent years, pulmonary arterial hypertension was considered as an untreatable disease. However, with the better knowledge in its pathobiology, new drugs have been developed. These new drugs can be divided in three main groups: 1. Prostacyclin analogs (Epoprostenol, iloprost, treprostinil); 2. Endothelin antagonists (Bosentan, sitaxsentan); and 3. Phosphodiesterase-5 inhibitors (Sildenafil). Numerous studies have evaluated the safety and efficacy of these drugs, showing significant improvement in exercise capacity, quality of life and time to worsening. Some of them have even showed a better survival when compared with conventional treatment. Despite these advances, pulmonary arterial hypertension remains an incurable disease, so the focus of new studies is the combination of two or more drugs with a different mechanism of action.

Cardiopulmonar complications in chronic liver diseases were described 100 years ago. Altough both hepatopulmonary sindrome and portopulmonary hypertension originates from liver damage, clinical findings and diagnosis are very different. These complications are important due to the highly deleterous impact on disease evolution and prognosis. Currently, there is not an ideal treatment for these diseases and liver transplantation should be adequately evaluated. In this review we analyze the most important issues on hepatopulmonary sindrome and portopulmonary hypertension. These complications,under the cornerstone of portal hypertension are characterized by pulmonary constriction and dilatation, respectively.

Objective: The pathogenesis of pulmonary hypertension (PHT) involves elevated levels of endothelin. Bosentan is a receptor antagonist used for the treatment of this disease. The purpose of the study is to assess the efficacy and tolerability of this drug in clinical practice., Method: A retrospective observational study of 10 patients with primary pulmonary hypertension (seven) and secondary to pulmonary thromboembolism (PTE), treated with bosentan. The decrease in systolic pulmonary artery pressure (SPAP) and the New York Heart Association (NYHA) functional classification were measured, together with treatment safety based on transaminase levels in the mid term and long term until the treatment period of two years was completed., Results: The decrease in SPAP between the beginning and the end of the treatment was not significant. Three of the ten patients began treatment in class II, five in class III and two in class IV. After 12 months of treatment, six patients were in class II, two in class IV, one patient died and another stopped the treatment due to toxicity. Four patients continued the treatment for 24 months, and the results were compared with those obtained during the first year: Two patients remained in class II, one patient deteriorated to class III and the four died., Conclusions: Bosentan is shown to be effective after six months of treatment, losing efficacy after two years. Bosentan gave satisfactory results in PHT secondary to PTE.

Objective: To assess the efficacy of treatment with sildenafil monotherapy in patients with pulmonary hypertension., Patients and Methods: An observational study was undertaken in 11 patients with pulmonary hypertension in functional class II or III who received treatment with sildenafil (150 mg/day). Seven of the patients had inoperable chronic thromboembolic pulmonary hypertension and 4 had pulmonary arterial hypertension. To assess treatment response, the following parameters were assessed during follow-up at 3, 6, and 12 months: exercise tolerance in the 6-minute walk test, change in functional class, and systolic pulmonary arterial pressure measured by echocardiography., Results: We observed a significant improvement in exercise tolerance, as shown by increased 6-minute walk distance after 3, 6, and 12 months of treatment (increases of 20, 67, and 95 m, respectively). All patients showed an improvement in functional class. The results of echocardiography did not reveal statistically significant differences in systolic pulmonary arterial pressure between baseline and 6 or 12 months of treatment. No significant adverse effects were observed, although sildenafil treatment was suspended in 1 patient due to persistent headache., Conclusions: The results of this study confirm that sildenafil is an effective drug for the management of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension both in the short term and medium to long term, and that the drug is well tolerated and shows few side effects.