Pulmonary capillary hemangiomatosis: a lesson learned

Pulmonary capillary hemangiomatosis (PCH) is a rare and controversial entity that is known to be a cause of pulmonary hypertension and is microscopically characterized by proliferation of dilated capillary-sized channels along and in the alveolar walls. Clinically, it is mostly seen in adults. Clinical features are characterized by nonspecific findings such as shortness of breath, cough, chest pain, and fatigue. It can be clinically indistinguishable from pre-capillary pulmonary arterial hypertension disorders such as primary pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. However, the diagnostic distinction, which usually requires a multidisciplinary approach, is crucial in order to avoid inappropriate treatment with vasodilator medications usually used for PAH treatment. Prognosis of PCH remains poor with lung transplant being the only definitive treatment. We report an autopsy case of pulmonary capillary hemangiomatosis unmasked at autopsy that was treated with a prostacyclin analog, usually contraindicated in such patients. We emphasize that this entity should always be on the differential diagnosis in a patient with pulmonary hypertension and requires great vigilance on the part of the clinician, radiologist and pathologist to make the diagnosis and guide appropriate management.

An Unusual Cause of an Uncommon Condition: Pulmonary Vein Stenosis.

Pulmonary vein stenosis in adults is historically a rare condition, but is becoming a recognised complication, albeit an uncommon one, of radiofrequency ablation around the pulmonary veins for treatment of atrial fibrillation. It may also be due to infiltrating mediastinal processes such as neoplasm or sarcoidosis. In this case report, a 55-year old man underwent resection of a mediastinal phaeochromocytoma involving the left atrial wall and the right inferior pulmonary vein. One year later he subsequently presented with increasing dyspnoea and atypical chest pain. Transthoracic echocardiogram showed severe pulmonary hypertension, right ventricular dilatation and dysfunction. Transesophageal echocardiogram demonstrated severe bilateral pulmonary vein stenosis with peak/mean gradients across the left pulmonary veins of about 25/20mmHg. The diagnosis was also confirmed on CT pulmonary angiography with 3D reconstruction. Open pulmonary vein stenting was planned but unfortunately the patient died suddenly before the procedure. Pulmonary vein stenosis is an uncommon but serious condition and may present with signs and symptoms indistinguishable from other conditions and may easily be missed. Clinicians should have a high index of suspicion when patients present with unexplained respiratory symptoms, especially in the context of catheter ablation or mediastinal processes such as neoplasm. Transesophageal echocardiography played an indispensible part in the correct diagnosis in our patient.

Pulmonary vein stenting for the treatment of severe pulmonary vein stenosis after catheter ablation of atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility, safety, and effectiveness of pulmonary vein stenting in patients with severe pulmonary vein stenosis (PVS) after catheter ablation of atrial fibrillation (AF).</p><p><b>METHODS</b>This retrospective analysis included 5 PVS patients (3 males, (54.1 ± 11.2) years old) confirmed by computed tomography angiography after catheter ablation of AF in Shanghai Chest Hospital from April 2010 to April 2013. After selective pulmonary vein angiography, stents were implanted in the pulmonary vein. Operation results were analyzed after the procedure.</p><p><b>RESULTS</b>All of 14 serious pulmonary vein stenosis from these 5 patients were treated with primary stent implantation (diameter: 7 or 8 mm, length: 12-23 mm). After stenting, degree of pulmonary vein stenosis decreased from (83 ± 16) % to (12 ± 4) % (P < 0.01), the minimal diameter of the stenosis was significantly increased from (1.7 ± 0.6) mm to (8.1 ± 0.7) mm (P < 0.01), trans-stenotic gradient decreased from (15 ± 5) mmHg (1 mmHg = 0.133 kPa) to (3 ± 2) mmHg (P < 0.05), mean pulmonary pressure measured by cardiac catheter decreased from (47 ± 5) mmHg to (28 ± 4) mmHg (P < 0.05). Dyspnea was improved after the procedure. There was no serious operation related complications. Six months after stenting, three patients still complained mild to moderate dyspnea, and in-stent restenosis was evidenced in seven pulmonary veins by computed tomography angiography. These stenosis was successfully dilated by repeated interventions with balloon dilation.</p><p><b>CONCLUSIONS</b>Stenting for severe pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation may be feasible and safe, and can improve hemodynamics and symptoms. In-stent stenosis is relatively frequent, and larger stents and early intervention may reduce the rates of in-stent restenosis.</p>

Hipertensão arterial pulmonar hereditária apresentando-se como venopatia oclusiva / Occlusive venopathy phenotype in hereditary pulmonary arterial hypertension / Hipertensión arterial pulmonar hereditaria presentándose como venopatía oclusiva

Um homem de 33 anos com hipertensão arterial pulmonar hereditária teve um diagnóstico confirmado de venopatia oclusiva e microvasculopatia. O paciente permaneceu estável por 3 anos e meio recebendo sildenafila via oral, 75 mg 3x/dia (teste de caminhada de seis minutos de 375 m vs 105 m basal), mas necessitou da adição de bosentana (125 mg 2x/dia) posteriormente. A despeito do desfecho fatal após 5 anos, as observações sugerem um utilidade potencial dos vasodilatadores como uma ponte para o transplante de pulmão em casos selecionados com envolvimento venocapilar significante. A ocorrência de lesões veno-oclusivas e capilares na forma familiar da hipertensão arterial pulmonar enfatiza as dificuldades com a atual classificação da doença.

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.

Un hombre de 33 años con hipertensión arterial pulmonar hereditaria tuvo un diagnóstico confirmado de venopatía oclusiva y microvasculopatía. El paciente permaneció estable 3,5 años recibiendo sildenafila vía oral, 75mg 3x/ día (test de caminata de seis minutos de 375m vs. 105m basal), pero necesitó adición de bosentánana (125mg 2x/día) posteriormente. A despecho del desenlace fatal después de 5 años, las observaciones sugieren una utilidad potencial de los vasodilatadores como un puente para el transplante de pulmón en casos seleccionados con compromiso venocapilar significativo. La ocurrencia de lesiones veno-oclusivas y capilares en la forma familiar de la hipertensión arterial pulmonar enfatiza las dificultades con la actual clasificación de la enfermedad.

Estenosis de venas pulmonares post ablación por radiofrecuencia / Pulmonary vein stenosis after radio frequency ablation

Es importante estar atento ante la aparición de síntomas respiratorios luego de la realización de un procedimiento de ablación por radiofrecuencia en el tratamiento de la fibrilación auricular, pues la estenosis de venas pulmonares (EVP) tiene una incidencia de entre 1 y 3% y puede aparecer hasta en los dos años posteriores al procedimiento1. Presentamos el caso de un paciente de 41 años de sexo masculino, que ingresó por un cuadro de hemoptisis y toracodinia de tres semanas de evolución, con antecedente de ablación por radiofrecuencia 6 meses antes de la admisión. La angiotomografía no evidenció tromboembolismo pulmonar (TEP) y la angiorresonancia detectó hipoperfusión deI lóbulo superior del pulmón izquierdo (LSI). Debido a los antecedentes de ablación se solicitó angiotomografía de venas pulmonares, que evidenció estenosis de la vena del LSI. Se realizó estudio hemodinámico con dilatación y colocación de stent.

Physicians should be alert to the occurrence of respiratory symptoms after radio frequency ablation for the treatment of atrial fibrillation. Pulmonary veins stenosis could appear with an incidence of between 1and 3% during the two years following the procedure. We present the case of a 41year-old-male patient admitted with a three weeks old hemoptysis and thoracodinia and a prior history of a radiofrecuency ablation procedure performed six months earlier. The angiotomography was not compatible with the diagnosis of pulmonary embolism and the angio-MRI detected hypoperfusion of the left upper pulmonary lobe. Consequently pulmonary veins angiotomography was requested, showing upper pulmonary lobe vein stenosis. An hemodynamic study with vein expansion and stent placement was successfully performed.

Clinical characteristics and survival of patients with pulmonary veno-occlusive disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the clinical presentation, diagnosis, treatment and outcome of patients with pulmonary veno-occlusive disease (PVOD).</p><p><b>METHODS</b>Data from patients diagnosed as PVOD from May 2008 to May 2011 in Shanghai Pulmonary Hospital, Tongji University were retrospectively reviewed.</p><p><b>RESULTS</b>During this period, 5 patients [4 female, aged from 12 to 42 (22 ± 12) years old] were diagnosed as PVOD. The durations from symptoms onset to PVOD diagnosis was 2 to 50 (16 ± 20) months and four of them were previously diagnosed as idiopathic pulmonary arterial hypertension. All patients at the time of PVOD diagnosis had a severely impaired WHO pulmonary hypertension functional class (3 in class III and 2 in class IV). Furthermore, all patients characterized by a typical sign of centrilobular ground-glass opacities in high-resolution computed tomography, a markedly reduction of diffusing capacity of the lung for carbon monoxide [(38 ± 12)% of predicted value] in pulmonary functional test and severely compromised cardio-pulmonary hemodynamics identified by right heart catheterization. All patients received conventional and pulmonary arterial hypertension specific therapies, and then followed-up regularly. Up to now, 4 out of 5 patients died due to refractory right heart failure. The durations from symptoms onset to death and from PVOD establish to death were 5 - 65 (27 ± 26) months and 1 - 16 (9 ± 9) months, respectively.</p><p><b>CONCLUSIONS</b>PVOD is a rare and malignant cardio-pulmonary disorder that often be misdiagnosed as idiopathic pulmonary arterial hypertension. Given the poor responses to modern pulmonary arterial hypertension specific therapies, lung transplantation remains the treatment of choice.</p>

Tratamento cirúrgico da estenose do túnel das veias pulmonares após Senning modificado / Surgical treatment of pulmonary venous baffle obstruction after modified Senning procedure

Paciente de 13 anos de idade, sexo masculino, submetido à correção de estenose de túnel das veias pulmonares (ETVP) após cirurgia de Senning modificada realizada aos 5 meses. O quadro clínico era de congestão pulmonar e broncopneumonias de repetição e o ecocardiograma confirmou ETVP. Uma angioplastia com balão foi realizada previamente à correção cirúrgica com circulação extracorpórea. A placa de pericárdio bovino empregada para ampliação do átrio direito retraiu-se e calcificou, levando a ETVP. A placa foi removida e o átrio direito foi ampliado com um retalho de politetrafluoretileno. O ecocardiograma transesofágico intraoperatório demonstrou redução significativa da estenose.

A 13-year-old male was admitted to undergoing correction of a pulmonary venous baffle stenosis (PVBS) after a modified Senning procedure was performed by the age of five months. Recurrent Pulmonary congestion and pneumonia episodes were followed by echocardiography and cardiac catheterization that confirmed PVBS. Previous catheter balloon angioplasty was attempted, and a surgical revision was done under cardiopulmonary bypass. The bovine pericardial patch used for augmentation of the right atrium, retracted and calcified producing PVBS. Stenotic area was excised and enlargement was done with polytetrafluoroethylene membrane. Intraoperative transesophageal echocardiogram showed relief of stenosis.

Drenagem anômala total das veias pulmonares: 29 anos de experiência em uma única instituição / Total anomalous pulmonary venous drainage: 29 years of experience in a single institution

FUNDAMENTO: A drenagem anômala total das veias pulmonares (DATVP) é uma doença rara, com incidência aproximada de 0,058 a 0,083:1.000 nascidos vivos. Apresenta mortalidade em torno de 80 por cento a 90 por cento no primeiro ano de vida, se não tratada precocemente. OBJETIVO: Utilizando a experiência de 29 anos de um único serviço, foram testadas possíveis variáveis relacionadas ao óbito hospitalar. MÉTODOS: Análise retrospectiva de 123 pacientes consecutivos operados com o diagnóstico de DATVP entre janeiro de 1979 e março de 2008. Foram incluídos apenas pacientes com DATVP isolada, excluídas as associações complexas. As variáveis foram testadas para a identificação da influência sobre os óbitos e da interferência da evolução temporal. RESULTADOS: As medianas de peso e idade foram de 4,1 kg e 120 dias, respectivamente. O subtipo anatômico supracardíaco foi o mais prevalente em todo o período analisado. Obstrução à drenagem esteve presente em 30 por cento dos casos, sendo o subtipo infracardíaco o mais associado. A taxa de mortalidade geral foi de 27 por cento, chegando a zero nos últimos cinco anos. Tanto na análise univariada quanto na multivariada, a presença de obstrução ao fluxo venoso pulmonar foi a única variável positivamente associada aos óbitos (p=0,005), independentemente da evolução temporal. A mortalidade dentre estes casos foi de 44 por cento. CONCLUSÃO: Após três décadas de evolução, pode-se observar melhora na mortalidade precoce da drenagem anômala total das veias pulmonares em nosso serviço, que atualmente apresenta níveis consistentes com a literatura. A obstrução à drenagem pulmonar continua sendo fator de mau prognóstico em nosso meio.

BACKGROUND: Total anomalous pulmonary venous drainage (TAPVD) is a rare disease, with an approximate incidence of 0.058 to 0.083:1,000 live births. It has a mortality rate of around 80 percent to 90 percent in the first year, if not treated early. OBJECTIVE: Using the 29-year experience of a single center, possible variables related to hospital death were tested. METHODS: Retrospective analysis of 123 consecutive patients with a diagnosis of TAPVD that underwent surgical treatment between January 1979 and March 2008. Only patients with isolated TAPVD were included and the complex associations were excluded. The variables were tested for the identification of their influence on death and of the interference of temporal evolution. RESULTS: The medians of weight and age were 4.1 kg and 120 days, respectively. The supracardiac anatomic subtype was the most prevalent throughout the analyzed period. Obstruction to drainage was present in 30 percent of the cases and the infracardiac subtype was the most frequently associated form. The general mortality rate was 27 percent, being equal to zero in the last five years. At both the univariate and multivariate analysis, the presence of obstruction to pulmonary venous flow was the only variable positively associated to the deaths (p = 0,005), regardless of the temporal evolution. The mortality among these cases was 44 percent. CONCLUSION: After three decades of evolution, an improvement in the early mortality rate of TAPVD can be observed in our service, which currently presents levels consistent with the literature. The obstruction to pulmonary drainage is still a bad prognostic factor in our country.

Tratamento de estenose de veia pulmonar após ablação percutânea de fibrilação atrial / Treatment of pulmonary vein stenosis after percutaneous ablation of atrial fibrillation / Tratamiento de estenosis de vena pulmonar tras ablación percutánea de fibrilación atrial

Neste relato de caso, descrevemos um paciente portador de fibrilação atrial (FA) persistente, submetido à ablação percutânea da FA pela técnica de isolamento extraostial das veias pulmonares, que desenvolveu uma estenose acentuada do óstio da veia pulmonar superior esquerda (VPSE), sem manifestar sintomas, diagnosticada pela angiotomografia de controle das veias pulmonares. O paciente foi submetido à angioplastia com implante de stent na VPSE com sucesso, resultando na normalização da perfusão pulmonar, verificado pela cintilografia pulmonar realizada 3 meses após a angioplastia.

This case report describes a patient with persistent atrial fibrillation (AF) submitted to radiofrequency catheter ablation of AF through the pulmonary vein antrum isolation technique, who developed a severe stenosis of the left superior pulmonary vein (LSPV), without presenting any symptoms. The diagnosis of the PV stenosis was made by a routine postprocedure computed tomography scan of the left atrium, and the patient was subsequently submitted to angioplasty with stenting of the LSPV, resulting in the normalization of pulmonary perfusion, as seen by ventilation/perfusion scan made three months after the LSPV angioplasty.

En este caso clínico, describimos a un paciente portador de fibrilación atrial (FA) persistente, sometido a ablación percutánea de la FA por la técnica de aislamiento extraostial de las venas pulmonares, que desarrolló una estenosis acentuada del ostio de la vena pulmonar superior izquierda (VPSI), sin manifestar síntomas, diagnosticada por la angiotomografía de control de las venas pulmonares. El paciente se sometió a angioplastia con implante de stent en la VPSI con éxito, resultando en la normalización de la perfusión pulmonar, verificado por el centellograma pulmonar realizada 3 meses tras la angioplastia.

Enfermedad pulmonar veno-oclusiva: reporte de un caso y revisión de la literatura / Pulmonary veno-occlusive disease: report of case and revision of the literature

La enfermedad pulmonar veno-oclusiva en una entidad de la cual se desconoce la incidencia real por que gran parte de los casos son subdiagnosticados o no son clasificados dentro de la hipertensión pulmonar primaria siendo esta una variante de la enfermedad primaria, afectando preferentemente la vasculatura pulmonar postcapilar. También conocida como esclerosis venosa pulmonar aislada, enfermedad obstructiva de las venas pulmonares o hipertensión pulmonar primaria de forma venosa. La EPVO es el resultado de la lesión de múltiples agresores asociado a una gran variedad de factores de riesgo. El diagnóstico de la enfermedad necesita de un componente clínico, radiológico y patológico. Para el manejo se ha reportado el uso de vasodilatadores, inmunosupresores, anticoagulantes y oxigeno con un pronóstico reservado con reporte de sobrevida limitados por la poca descripción de casos. Reportamos un caso de enfermedad pulmonar veno-oclusiva el cual se diagnostico en la institución.

Doença veno-oclusiva pulmonar: alternativas diagnósticas e terapêuticas / Pulmonary veno-occlusive disease: diagnostic and therapeutic alternatives

A doença veno-oclusiva pulmonar (DVOP) é uma causa rara de hipertensão pulmonar. A biópsia cirúrgica era usualmente necessária para seu diagnóstico; entretanto, sua morbidade, mortalidade e seu impacto limitado levantou a discussão sobre o diagnóstico não-invasivo. Apresentamos um caso de uma paciente com dispnéia progressiva, hipoxemia e hipertensão pulmonar no cateterismo. A tomografia computadorizada revelou espessamento septal e micronódulos difusos. O lavado broncoalveolar revelou hemorragia alveolar oculta. Iniciou-se tratamento com antagonista da endotelina, que resultou em melhora clínica e funcional. A hemorragia alveolar oculta é uma característica da DVOP capaz de diferenciá-la da hipertensão pulmonar idiopática. Acreditamos que sua presença, associada à tomografia característica, seja suficiente para o diagnóstico de DVOP.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Surgical biopsy was usually required for diagnostic confirmation. However, the morbidity, mortality and limited benefit of this procedure have generated discussion regarding noninvasive diagnostic techniques. We present the case of a female patient with progressive dyspnea, hypoxemia and pulmonary hypertension, the last diagnosed via catheterization. Computed tomography revealed septal thickening and diffuse micronodules. Bronchoalveolar lavage revealed occult alveolar hemorrhage. Treatment with an endothelin antagonist was started, resulting in symptomatic and functional improvement. Occult alveolar hemorrhage differentiates PVOD from idiopathic pulmonary hypertension. We believe that this finding, in combination with characteristic tomographic findings, is sufficient to establish a diagnosis of PVOD.

Tuberculosis infantil: un enfoque actual / Childhood tuberculosis a current approach

La tuberculosis es un problema de tal magnitud que la Organización Mundial de la Salud la ha declarado una emergencia global. El porcentaje exacto de niños con tuberculosis se estima que es de 3 a 13% de todos los casos.La patogénesis y el cuadro clínico de la tuberculosis infantil presentan características particulares debido a la inmadurez del sistema inmune y a la escasez de manifestaciones clínicas en el niño aún con tuberculosis activa.El diagnóstico es difícil y se basa en una combinación de criterios: 1-. Contacto con un adulto con tuberculosis.2-. Cuadro clínico sugestivo (anorexia, falla en el medro,fiebre persistente, apatía, etc). 3-. Prueba de tuberculina positiva. 4-. Anormalidades en la radiografía de tórax(adenopatías hiliares, patrón miliar, cavernas, etc). 5-. Baciloscopía o cultivo positiva. 6-. Granuloma específico en resultado de anatomía patológica. El tratamiento se basa en una combinación de Isoniacida, Rifampicina, Pirazinamida y Etambutol (o Estreptomicina) por dos meses,seguido de Isoniacida y Rifampicina por cuatro meses. La cuarta droga puede ser omitida si la drogorresistencia es poco probable o la enfermedad es mínima. La tuberculosis multidrogorresistente puede requerir de cuatro a siete drogas con una duración más prolongada y debe ser manejada por un experto en tuberculosis. La adherencia al tratamiento es esencial para el éxito de la terapia. La prevención se basa en el tratamiento de la enfermedad activa, tratamiento de la infección tuberculosa latente y la vacunación con BCG...

Changes in the Lung after Pulmonary Hypertension Induced by Obstruction of the Pulmonary Vein in Rats / 대한흉부외과학회지

BACKGROUND: Experimental studies of vascular remodeling in the pulmonary arteries have been performed actively. These models required a persistent vascular insult for intimal injury induced by chronic hypoxia, monocrotaline intoxication or chronic air embolism and characterized medial hypertrophy and neointimal formation by active synthesis of the extracellular matrix protein. The purpose of this study was to determine the pattern of pulmonary vascular remodeling after obstruction of the pulmonary vein. MATERIAL AND METHOD: Obstruction of the right pulmonary vein with a metal clip was performed in Sprague-Dawley rats (352+/-18 g, n=10) to cause pulmonary vascular disease. Fifteen days later, experimental studies were done and finally the both lungs and hearts were extirpated for experimental measurement. Pulmonary arterial pressure, weight ratio of right ventricle (RV) to left ventricle (LV) and ventricular septum (S) (RV/LV+S weight ratio), and pulmonary artery morphology (percent wall thickness, %WT) were evaluated and compared with normal control groups. RESULT: Pulmonary hypertension (38+/-12 mmHg vs 13+/-4 mmHg; p<0.05) and right ventricular hypertrophy (right ventricular/left ventricular and septal weight ratio, 0.52+/-0.07 vs 0.35+/-0.04; p<0.05) with hypertrophy of the muscular layer of the pulmonary arterial wall (percent wall thickness, 22.4+/-6.7% vs 6.7+/-3.4%; p<0.05) were developed by 15 days after obstruction of the pulmonary vein. CONCLUSION: Obstruction of the pulmonary vein developed elevation of pulmonary blood pressure and medial hypertrophy of the pulmonary artery. These results are a part of the characteristic vascular remodeling. Theses results demonstrate that obstruction of the pulmonary vein can develope not only high pulmoanry blood flow of contralateral lung but also intima injury inducing vascular remodeling.

Angioplasty of congenital pulmonary vein stenosis.

We present a unique case of idiopathic pulmonary vein stenosis in an adult who presented with progressive dyspnea and severe pulmonary arterial hypertension. Magnetic resonance imaging confirmed the diagnosis. The patient was treated by balloon angioplasty and is well at 6 months post-treatment follow-up. The etiology of pulmonary vein stenosis in this case is difficult to ascertain, but is likely to be congenital.

Pulmonary veno-occlusive disease in a patient with a history of Hashimoto's thyroiditis.

Pulmonary veno-occlusive disease (PVOD), a rapidly progressive and fatal disorder, is a rare cause of pulmonary hypertension. We report the occurrence of PVOD in a female patient with Hasimoto's thyroiditis. This report emphasises that PVOD can co-exist with Hashimoto's thyroiditis and a high index of clinical suspicion is required to confirm the diagnosis of PVOD.

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.