Safety and efficacy of epoprostenol therapy in pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. There is no proven medical therapy to treat these diseases, and lung transplantation is thought to be the only cure. Administration of vasodilators including epoprostenol sometimes causes massive pulmonary edema and could be fatal in these patients. METHODS AND RESULTS: Eight patients were treated with epoprostenol for 387.3±116.3 days (range, 102-1,063 days), who were finally diagnosed with PVOD or PCH by pathological examination. The maximum dose of epoprostenol given was 55.3±10.7 ng·kg(-1)·min(-1) (range, 21.0-110.5 ng·kg(-1)·min(-1)). With careful management, epoprostenol therapy significantly improved the 6-min walk distance (97.5±39.2 to 329.4±34.6 m, P<0.001) and plasma brain natriuretic peptide levels (381.3±136.8 to 55.2±14.4 pg/ml, P<0.05). The cardiac index significantly increased from 2.1±0.1 to 2.9±0.3 L·min(-1)·m(-2) (P<0.05). However, pulmonary artery pressure and pulmonary vascular resistance were not significantly reduced. For 4 patients, epoprostenol therapy acted as a bridge to lung transplantation. For the other patients who had no chance to undergo lung transplantation, epoprostenol therapy was applied for 528.0±216.6 days and the maximum dose was 63.9±19.0 ng·kg(-1)·min(-1). CONCLUSIONS: This study data suggest that cautious application of epoprostenol can be considered as a therapeutic option in patients with PVOD and PCH.

Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension.

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 µg·kg⁻¹·min⁻¹ for 5 min and 2 µg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 µg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

A phase III, multicenter, collaborative, open-label clinical trial of sildenafil in Japanese patients with pulmonary arterial hypertension.

BACKGROUND: There is evidence that phosphodiesterase type-5 is effective for the treatment of pulmonary arterial hypertension (PAH). METHODS AND RESULTS: A phase III, multicenter, open-label clinical trial of sildenafil 20mg t.i.d. was conducted in 21 Japanese patients with PAH to examine its efficacy, safety, and pharmacokinetics. The present trial consisted of a screening period and 12-week treatment. Patients who were enrolled in the present trial increased their 6-min walking distance of administration increased at week 12 by 84.2m from baseline. Hemodynamic parameters (eg, mean pulmonary artery pressure and pulmonary vascular resistance), Borg dyspnea scores, and plasma brain natriuretic peptide concentrations also improved compared to baseline. Most patients improved or sustained WHO functional class. Seven subjects, who were examined for the pharmacokinetics of sildefanil, showed relatively large interindividual variations in the C(max), AUC(0-8), C(ss,av), and C(trough) of the drug. Any serious adverse events, severe adverse events, and deaths were not observed. Most of events of undeniable causality were mild or moderate in severity. Sildefanil was well tolerated by the subjects. CONCLUSIONS: Sildenafil 20mg t.i.d. was effective and safe for Japanese patients with PAH.

Marked hemodynamic improvements by high-dose epoprostenol therapy in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: The appropriate dose range of epoprostenol is thought to be 25-40 ng · kg(-1) · min(-1) based on the results of previous studies showing that epoprostenol therapy reduced mean pulmonary artery pressure (mPAP) by 12-22% and pulmonary vascular resistance (PVR) by 32-53% compared with baseline values in patients with idiopathic pulmonary arterial hypertension (IPAH). However, the efficacy of treatment of IPAH patients with epoprostenol >40 ng · kg(-1) · min(-1) has not been determined and this was the aim of the present study. METHODS AND RESULTS: The study group comprised 16 consecutive patients, none of whom died; 2 dropped out because they could not be titrated up as needed to the highest effective epoprostenol dose. Hemodynamics were evaluated in 14 IPAH patients who received high-dose epoprostenol monotherapy. The mean epoprostenol dosage was 107 ± 40 ng · kg(-1) · min(-1) (range, 54-190 ng · kg(-1) · min(-1)) and the mean duration of high-dose epoprostenol therapy was 1,355 ± 627 days (range, 582-2,410 days). Significant decreases from baseline values were seen in mPAP (from 66 ± 16 to 47 ± 12 mmHg, P<0.001) and PVR (from 21.6 ± 8.3 to 6.9 ± 2.9 Wood units, P<0.001). Compared with the baseline state, high-dose epoprostenol therapy reduced mPAP by 30% and PVR by 68%. CONCLUSIONS: The present study suggests high-dose epoprostenol therapy is a new treatment strategy for IPAH.

Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon.

AIMS: To determine the effect of intravenous administration of nicorandil on slow coronary flow (SCF) phenomenon in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In a preliminary study, 6 mg of nicorandil showed optimal efficacy for vasodilatation without causing significant haemodynamic instability. In the main study, a total of 408 patients were randomly assigned to receive intravenous administration of 6 mg of nicorandil immediately before PCI. The number of patients in the nicorandil group was 206 [acute coronary syndrome (ACS): 47, non-ACS: 159] and that in the control group was 202 (ACS: 61, non-ACS: 141). Nicorandil significantly decreased the incidence of post-procedural SCF phenomenon in both the ACS and non-ACS groups. The rate of target vessel revascularization (TVR) was significantly lower in the nicorandil group than in the control group in ACS patients. CONCLUSION: Our simple procedure prevented SCF phenomenon not only in patients with ACS but also in patients with non-ACS without any adverse effect. Additionally our procedure reduced the rate of TVR in patients with ACS.

Continuous epoprostenol therapy and septal defect closure in a patient with severe pulmonary hypertension.

A 31-year-old woman with exertional dyspnea diagnosed as having atrial septal defect (ASD) with severe pulmonary hypertension (PH). Intravenous epoprostenol therapy was started to improve PH. Although pulmonary arterial pressure decreased, her symptoms remained in class III of WHO functional class, probably because of exacerbation of the left-to-right shunt caused by the reduction of pulmonary vascular resistance (PVR). Transcatheter atrial septal closure was therefore performed. Soon after the procedure, additional reduction in pulmonary arterial pressure was achieved. Her symptoms improved and oxygen inhalation was discontinued. One year after the procedure, although intravenous epoprostenol was still required, her symptoms had improved to class I of WHO functional class without exacerbation of PH. Transcatheter atrial septal closure after lowering PVR by intravenous epoprostenol would be a novel therapy for patients with ASD accompanied by PH.

The ratio of the atrial areas reflects the clinical status of patients with pulmonary arterial hypertension.

PURPOSE: Echocardiography is useful not only for detecting pulmonary hypertension (PH) but also for estimating the severity of PH by evaluating various morphological changes of the heart caused by pressure and volume overload and by ventricular interaction. We investigated whether a novel echocardiographic index, i.e., the ratio of the atrial areas (RA/LA), would be useful for evaluating the clinical status of patients with pulmonary arterial hypertension (PAH) treated with intravenous epoprostenol. METHODS: We introduced epoprostenol therapy for seven PAH patients without severe tricuspid regurgitation. We evaluated clinical criteria indicative of prognosis, for example World Health Organization functional class (WHO-FC), brain natriuretic peptide (BNP) level, echocardiographic indices such as indexed RA area and RA/LA, and hemodynamics before and one year after intravenous epoprostenol therapy. RESULTS: There were significant improvements in both RA/LA (2.5 ± 1.0, 1.3 ± 0.4, P < 0.001) and indexed RA area (22.5 ± 8.9, 14.5 ± 5.8, P < 0.001). The improvement in RA/LA was more sensitive than that in indexed RA area (P < 0.01). Moreover, RA/LA was significantly correlated with WHO-FC (r = 0.50, P < 0.01) and BNP level (r = 0.82, P < 0.01). CONCLUSIONS: RA/LA is useful for evaluating the clinical status of patients with PAH treated with intravenous epoprostenol.

[Continuous intravenous prostacyclin therapy].

Intravenous prostacyclin therapy has been established as the standard therapy for patients with pulmonary arterial hypertension. Thus, it is strongly recommended by the guidelines in United States, Europe, and Japan on treatment of severely ill patients with pulmonary arterial hypertension based on the several controlled trials. The half-life of epoprostenol is so short that it needs to be administered by continuous infusion pump and indwelled central venous catheter, which could induce life-threatening adverse events such as pump malfunction, catheter obstruction and infection. Despite such complexities, it should not be hesitated to introduce the most effective treatment--continuous intravenous prostacyclin therapy--for patients with severe pulmonary arterial hypertension.

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are categorized as Group 1' in the clinical classification of pulmonary hypertension. No medical therapy has been proven to be effective in patients with PVOD/PCH. Imatinib is a molecular targeted drug and was expected to be effective in patients with pulmonary arterial hypertension. We evaluated its efficacy and safety in patients with PVOD/PCH. METHODS: In the present observational study, 9 patients with PVOD/PCH received imatinib. Clinical data including exercise capacity and hemodynamics at baseline and at follow-up were compared. Survival rate of patients treated with imatinib was compared to those of 7 patients who did not treated with imatinib. RESULTS: Imatinib was prescribed at doses of 100-400 mg/day and was well-tolerated. At follow-up, World Health Organization functional class and brain natriuretic peptide levels significantly improved. Mean pulmonary arterial pressure was significantly reduced (from 56.8 ± 8.3 to 43.7 ± 9.0 mmHg) with preserved cardiac index. Patients were treated with imatinib for 797.2 ± 487.0 days. Seven patients (77.8%) died and 2 patients (22.2%) underwent lung transplantation. Mean survival time in patients treated with imatinib therapy was 1493.7 ± 196.3 days (95% confidence interval, 1108.9-1878.5 days), significantly longer than those without imatinib treatment (713.0 ± 258.1 days, log-rank test, P = 0.04). CONCLUSIONS: Imatinib improved exercise capacity, hemodynamics and survival in patients with PVOD/PCH. In patients with PVOD/PCH, who have no effective medical therapy available, imatinib might function as a bridge to lung transplantation, and may become a potential therapeutic option to improve their survival.

Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH. METHODS AND RESULTS: Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor (PDGF), PSL was added at different concentrations and cell proliferation was assessed by 3H-thymidine incorporation. PSL (2x10(-4) and 2x10(-3) mol/L) significantly inhibited PDGF-stimulated proliferation (P<0.05) of SMCs from patients with IPAH but did not affect cell viability of SMCs, as confirmed by trypan blue staining. In cell cycle analysis using a microscope-based multiparameter laser scanning cytometer, PSL inhibited the progression of SMCs from G(0)/G1 to the S phase. This inhibition was associated with increased p27 expression level. PSL (2x10(-4) mol/L) also inhibited PDGF-induced SMC migration. CONCLUSIONS: Our results indicate that PSL has an antiproliferative effect on cultured SMCs of pulmonary arteries from patients with IPAH and suggest that PSL may be potentially useful therapeutically in patients with IPAH.

Continuous positive airway pressure ameliorated severe pulmonary hypertension associated with obstructive sleep apnea.

A 52-year-old obese woman was admitted to our institution for evaluation of dyspnea and pulmonary hypertension (PH). Polysomnography revealed severe obstructive sleep apnea (OSA) with an apnea hypopnea index of 99.8. Treatment with nocturnal continuous positive airway pressure (CPAP) resulted in correction of daytime hypoxemia, hypercapnia, and near-normalization of pulmonary artery pressure. To our knowledge, this is the most severe case of OSA-associated PH (approximately70 mmHg) reported to date, and it was successfully treated with nocturnal CPAP. This case demonstrates that OSA should be considered and polysomnography performed in all patients with PH, irrespective of severity, and that nocturnal CPAP has therapeutic effects on both OSA and daytime PH.

Novel Angiographic Classification of Each Vascular Lesion in Chronic Thromboembolic Pulmonary Hypertension Based on Selective Angiogram and Results of Balloon Pulmonary Angioplasty.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions. METHODS AND RESULTS: We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success rate was higher, and the complication rate was lower in ring-like stenosis and web lesions. The total occlusion lesions had the lowest success rate. Tortuous lesions were associated with a high complication rate and should be treated only by operators with extensive experience with BPA. CONCLUSIONS: We modified the previous angiographic classification and established a new classification for each vascular lesion. We clarified that the outcome and complication rate of the BPA are highly dependent on the lesion characteristics.

Carvedilol decreases elevated oxidative stress in human failing myocardium.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating beta-blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results- Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects (P<0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9+/-4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22+/-8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% (P<0.005) along with amelioration of heart failure. CONCLUSIONS: Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.

Equivalence of flow velocities through bilateral pulmonary vein anastomoses in bilateral living-donor lobar lung transplantation.

BACKGROUND: Intraoperative transesophageal echocardiography (TEE) during lung transplantation is useful for monitoring cardiac condition and pulmonary vascular anastomoses to detect vascular complications, but the parameters for evaluation by TEE during lung transplantation have not been established. METHODS: We performed intraoperative TEE on 17 patients during living-donor lobar lung transplantation (LDLLT) and investigated the usefulness of measurement of peak flow velocities through bilateral pulmonary vein (PV) anastomoses and evaluation of the equivalence. RESULTS: The peak flow velocities through bilateral PV anastomoses were almost equivalent in 14 patients without complications and were not equivalent in 3 patients with complications such as vascular stenosis and peripheral atelectasis. CONCLUSIONS: The flow velocities through the bilateral PV anastomoses are shown to be nearly equivalent during bilateral LDLLT, and the equivalence may be one factor for predicting the success of LDLLT.

Improved survival after living-donor lobar lung transplantation.

OBJECTIVE: Survival after living-donor lobar lung transplantation has been reported to be similar to that after cadaveric lung transplantation. The purpose of this study was to summarize our 5-year experience of living-donor lobar lung transplantation for critically ill patients. METHODS: Between October 1998 and April 2004, we performed living-donor lobar lung transplantation in 30 critically ill patients with various lung diseases, including 5 (17%) patients on a ventilator. Mean age was 30.4 years (range, 8-55 years). Postoperative management included slow weaning from a ventilator, relatively low-dose immunosuppressants, and careful rejection monitoring on the basis of radiographic and clinical findings without transbronchial lung biopsy. RESULTS: The average duration of mechanical ventilation was 15.4 days, intensive care unit stay was 23.5 days, and hospital stay was 64.6 days. Clinically judged acute rejection occurred at an average rate of 1.5 episodes per patient, but infection occurred in only one patient during the first month. In spite of the complicated postoperative course, all patients were discharged without oxygen inhalation. Four patients had unilateral bronchiolitis obliterans syndrome, but the decrease in their forced expiratory volume in 1 second values stopped within 9 months. All 30 recipients are currently alive, with a follow-up period of 1 to 66 months. All donors have returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung transplantation can be applied to both pediatric and adult patients with very limited life expectancies. It might provide better survival than conventional cadaveric lung transplantation.

Effect of a kink in unilateral pulmonary artery anastomosis on velocities of blood flow through bilateral pulmonary vein anastomoses in living-donor lobar lung transplantation.

Intraoperative transesophageal echocardiography is generally performed to detect vascular complications during lung transplantation. We report a case with a kink in pulmonary artery (PA) anastomosis suggested by an abnormal flow profile of pulmonary vein (PV) anastomoses during living-donor lobar lung transplantation. During the transplantation, velocity of blood flow through the right PV anastomosis showed abnormal elevation. Then, the patient's PA pressure elevated abnormally and a kink in the left PA anastomosis was found. Careful monitoring of PV anastomoses may enable detection of not only an abnormality of PV anastomoses but also that of PA anastomoses, especially in living-donor lobar lung transplantation.

Differences between flow profiles of pulmonary vein anastomoses affected by peripheral atelectasis in cadaveric and bilateral living-donor lobar lung transplantations.

We report two cases of peripheral atelectasis during cadaveric and living-donor lobar lung transplantation, which had different effects on the flow profile of pulmonary vein (PV) anastomoses. In the patient who underwent living-donor lobar lung transplantation, we detected the increase in the velocity of blood flow through the left PV anastomosis by intraoperative transesophageal echocardiography. Then peripheral atelectasis occurred in the transplanted left lung lobe. On the other hand, in the patient who underwent cadaveric bilateral lung transplantation, peripheral atelectasis occurred, but no changes in velocities of blood flow through PV anastomoses were detected by intraoperative transesophageal echocardiography. This difference may have been caused by the difference in sizes of pulmonary beds of transplanted grafts. These findings indicate the necessity of careful monitoring of PV anastomoses, especially in cases of living-donor lobar lung transplantation.

Catecholamine support at the initiation of epoprostenol therapy in pulmonary arterial hypertension.

RATIONALE: Epoprostenol is a first-line therapy for patients with pulmonary arterial hypertension (PAH) in World Health Organization functional class IV who often have low cardiac output and hypotension. However, initiation of epoprostenol can cause hemodynamic collapse in these vulnerable patients. Inotropic agent support may prevent the hemodynamic instability caused by initiation of epoprostenol; however, a protocol for supportive therapy has not been established. OBJECTIVES: To assess the reliability and prognostic effects of dobutamine and dopamine support at the initiation of epoprostenol therapy in patients with PAH. METHODS: We initiated epoprostenol therapy in 71 patients with PAH. Hemodynamics at the initiation of epoprostenol were measured by right heart catheterization. We initiated dobutamine when a patient's mixed venous oxygen saturation was less than 60% or cardiac index was less than 2.0 L/min/m(2) or when right ventricular failure was clinically suspected. We initiated dopamine when a patient's systolic blood pressure was less than 90 mm Hg or urine volume was less than 20 ml/h. MEASUREMENTS AND MAIN RESULTS: At the initiation of epoprostenol, dobutamine and/or dopamine were required to support 46 patients according to protocol. Eight patients died during the hospitalization and one patient received a living-donor lobar lung transplant after the initiation of epoprostenol therapy. Neither inotropic agent was an independent risk factor for short-term mortality (dobutamine: hazard ratio, 1.63; 95% confidence interval, 0.33-8.11; dopamine: hazard ratio, 0.22; 95% confidence interval, 0.03-1.70). Sixty-two patients were discharged for home infusion of epoprostenol. Transplant-free survival rates at 5 years were 80.0% for patients who did not require inotropic support at the start of epoprostenol and 76.6% for patients with who did require dopamine and/or dobutamine support (P = 0.45). CONCLUSIONS: Temporary use of dobutamine and dopamine appears to be safe for hemodynamic support at the initiation of epoprostenol therapy for selected patients with PAH with low cardiac output and hypotension. The protocol presented here requires validation at other centers.

Current trends in the management of pulmonary hypertension associated with respiratory disease in institutions approved by the Japanese Respiratory Society.

BACKGROUND: Pulmonary hypertension (PH) often correlates with respiratory disease severity. Right heart catheterization (RHC) is recommended for the definitive diagnosis of PH associated with respiratory disease (R-PH). However, no previous studies have evaluated the perceived necessity for pulmonologists to use RHC for R-PH diagnosis, or the management of R-PH in Japan. METHODS: Questionnaires were mailed to 855 institutions, approved by the Japanese Respiratory Society. Questions included the prevalence and necessity of RHC and other methods in R-PH diagnosis, and current trends in the treatment of R-PH. RESULTS: Questionnaires were returned from 289 institutions (34%). Patients with R-PH were examined by pulmonologists in 89% of institutions; some pulmonologists performed echocardiography (15%) and some RHC (13%). Echocardiography was used to diagnose R-PH in 99% of institutions and RHC was used in 36%. RHC was considered in cases of suspected PH in 49% of institutions and prior to initiation of pulmonary arterial hypertension (PAH)-specific therapy in 57%. Of patients diagnosed with R-PH, 47% were treated with ambulatory oxygen therapy. Furthermore, 98 of 145 institutions used PAH-specific therapy to treat R-PH. Of the 1355 patients who underwent RHC as a part of PH evaluation, 29% were confirmed to have PH, and 8% had severe PH with a mean pulmonary arterial pressure of ≥35mmHg. CONCLUSIONS: The current diagnostic and treatment modalities for R-PH in Japan were evaluated. Although few pulmonologists perform RHC for R-PH diagnosis in Japan, more than half consider using RHC for patients before initiating PAH-specific therapy.

Imatinib is partially effective for the treatment of pulmonary capillary hemangiomatosis.

A 43-year-old man presented with dyspnea on exertion. Right heart catheterization demonstrated pulmonary arterial hypertension (PAH). He was treated with bosentan, sildenafil and intravenous epoprostenol. Despite the administration of such intensive therapy, the patient's condition deteriorated to a World Health Organization functional class (WHO-FC) of IV. He participated in a clinical trial of imatinib for PAH. After three months of treatment with imatinib, the chest X-ray and echocardiography findings improved, and the WHO-FC class was III. One year after, however, the PAH worsened again, and the patient died 2.6 years after the first diagnosis. At autopsy, patchy capillary proliferation was observed in the lungs. The definitive diagnosis was pulmonary capillary hemangiomatosis.