Artificial intelligence-based model for predicting pulmonary arterial hypertension on chest x-ray images.

BACKGROUND: Pulmonary arterial hypertension is a serious medical condition. However, the condition is often misdiagnosed or a rather long delay occurs from symptom onset to diagnosis, associated with decreased 5-year survival. In this study, we developed and tested a deep-learning algorithm to detect pulmonary arterial hypertension using chest X-ray (CXR) images. METHODS: From the image archive of Chiba University Hospital, 259 CXR images from 145 patients with pulmonary arterial hypertension and 260 CXR images from 260 control patients were identified; of which 418 were used for training and 101 were used for testing. Using the testing dataset for each image, the algorithm outputted a numerical value from 0 to 1 (the probability of the pulmonary arterial hypertension score). The training process employed a binary cross-entropy loss function with stochastic gradient descent optimization (learning rate parameter, α = 0.01). In addition, using the same testing dataset, the algorithm's ability to identify pulmonary arterial hypertension was compared with that of experienced doctors. RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve for the detection ability of the algorithm was 0.988. Using an AUC threshold of 0.69, the sensitivity and specificity of the algorithm were 0.933 and 0.982, respectively. The AUC of the algorithm's detection ability was superior to that of the doctors. CONCLUSION: The CXR image-derived deep-learning algorithm had superior pulmonary arterial hypertension detection capability compared with that of experienced doctors.

Modification of pulmonary endarterectomy to prevent neurologic adverse events.

PURPOSE: Neurologic adverse events (NAEs) are a major complication after pulmonary endarterectomy (PEA) performed under periods of deep hypothermic circulatory arrest (HCA) for chronic thromboembolic pulmonary hypertension. We modified the PEA strategy to prevent NAEs and evaluated the effectiveness of these modifications. METHODS: We reviewed the surgical outcomes of 87 patients divided into the following three groups based on the surgical strategy used: group S (n = 49), periods of deep HCA with alpha-stat strategy; group M1 (n = 19), deep HCA with modifications of slower cooling and rewarming rates and the pH-stat strategy for cooling: and group M2 (n = 13), multiple short periods of moderate HCA. RESULTS: PEA provided significant improvement of pulmonary hemodynamics in each group. Sixteen (29%) of the 49 group S patients suffered NAEs, associated with total circulatory arrest time (cutoff, 57 min) and Jamieson type I disease. The Group M1 and M2 patients did not suffer NAEs, although the group M1 patients had prolonged cardiopulmonary bypass (CPB) and more frequent respiratory failure. CONCLUSIONS: NAEs were common after PEA performed under periods of deep HCA. The modified surgical strategy could decrease the risk of NAEs but increase the risk of respiratory failure. Multiple short periods of moderate HCA may be useful for patients at risk of NAEs.

Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be associated with chronic inflammation; however, the underlying mechanism remains unclear. Recently, altered gut microbiota were found in patients with pulmonary arterial hypertension (PAH) and in experimental PAH models. The aim of this study was to characterize the gut microbiota in patients with CTEPH and assess the relationship between gut dysbiosis and inflammation in CTEPH. METHODS: In this observational study, fecal samples were collected from 11 patients with CTEPH and 22 healthy participants. The abundance of gut microbiota in these fecal samples was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Inflammatory cytokine and endotoxin levels were also assessed in patients with CTEPH and control participants. RESULTS: The levels of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were elevated in patients with CTEPH. Plasma endotoxin levels were significantly increased in patients with CTEPH (P < 0.001), and were positively correlated with TNF-α, IL-6, IL-8, and MIP-1α levels. The 16S rRNA gene sequencing and the principal coordinate analysis revealed the distinction in the gut microbiota between patients with CTEPH (P < 0.01) and control participants as well as the decreased bacterial alpha-diversity in patients with CTEPH. A random forest analysis for predicting the distinction in gut microbiota revealed an accuracy of 80.3%. CONCLUSION: The composition of the gut microbiota in patients with CTEPH was distinct from that of healthy participants, which may be associated with the elevated inflammatory cytokines and endotoxins in CTEPH.

Interventricular septal curvature as an additional echocardiographic parameter for evaluating chronic thromboembolic pulmonary hypertension: a single-center retrospective study.

BACKGROUND: Noninvasive estimation of the actual systolic pulmonary artery pressure measured via right-sided heart catheterization (sPAPRHC) is vital for the management of pulmonary hypertension, including chronic thromboembolic pulmonary hypertension (CTEPH). Evaluation related to the interventricular septum (IVS) is generally performed with only visual assessment and has been rarely assessed quantitatively in the field of echocardiography. Thus, this study aimed to investigate the utility of echocardiographic IVS curvature to estimate sPAPRHC in patients with CTEPH. METHODS: Medical records of 72 patients with CTEPH were studied retrospectively. We estimated sPAPRHC using echocardiographic IVS curvature (esPAPcurv) and left ventricular eccentricity index (esPAPLVEI), and compared their ability to predict sPAPRHC with estimated sPAPRHC using tricuspid regurgitant pressure gradient (esPAPTRPG). RESULTS: IVS curvature and LVEI were significantly correlated with sPAPRHC (r = - 0.52 and r = 0.49, respectively). Moreover, the IVS curvature was effective in estimating the sPAPRHC of patients with trivial tricuspid regurgitation (r = - 0.56) and in determining patients with sPAPRHC ≥ 70 mmHg with higher sensitivity (77.0%) compared to those with esPAPTRPG and esPAPLVEI. CONCLUSION: Our results indicate that the echocardiographic IVS curvature could be a useful additional tool for estimating sPAPRHC in CTEPH patients for whom accurate estimation of sPAPRHC using tricuspid regurgitant pressure gradient is challenging.

Characteristics of patients meeting the new definition of pre-capillary pulmonary hypertension (Nice 2018) in a single Japanese pulmonary hypertension center.

BACKGROUND: The 6th World Symposium on Pulmonary Hypertension (Nice 2018) proposed a new definition of pre-capillary pulmonary hypertension (PH) as a condition with mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU). The characteristics and prognosis of patients with pre-capillary PH, according to this new definition, is unclear. Therefore, we determined the characteristics and survival of patients with borderline pre-capillary PH. METHODS: We retrospectively enrolled 683 patients who underwent their first right heart catheterization at Chiba University, Japan. Among them, 489 patients met the pre-capillary PH requirement with mPAP ≥ 25 mmHg (conventional pre-capillary PH group), while 22 patients met the borderline pre-capillary PH criteria (borderline pre-capillary PH group). Additionally, 16 patients with a mean PAP of 20-25 and PVR of 2-3 WU were also examined. RESULTS: The borderline pre-capillary PH group comprised 4.3% of the total patients with pre-capillary PH, and the majority was in Group 3 (40.9%) or 4 (45.5%). The survival of the borderline pre-capillary PH group tended to be better than that of the conventional pre-capillary PH group. The prognosis of Group3 PH was the worst among the patients with borderline precapillary PH. There was no significant difference in survival between the borderline pre-capillary PH group with PVR ≥ 3 WU and that with PVR of 2-3 2WU, although none of the patients in the latter group died due to right heart failure. CONCLUSIONS: This is the first study conducted in a PH center in an Asian country to reveal the characteristics of patients with pre-capillary PH, according to the Nice 2018 definition. They comprised 4.3% of the total population with pre-capillary PH, and the majority of the pre-capillary PH cases were in either Group3 or 4. The prognosis may be affected by the patients' underlying diseases. Further prospective studies are needed to determine whether the new definition, including the PVR cut-off, is beneficial in clinical practice.

Vascular involvement in chronic thromboembolic pulmonary hypertension is associated with spirometry obstructive impairment.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension caused by persistent thromboembolism of the pulmonary arteries. In clinical practice, CTEPH patients often show obstructive ventilatory impairment, even in the absence of a smoking history. Recent reports imply a tendency for CTEPH patients to have a lower FEV1.0; however, the mechanism underlying obstructive impairment remains unknown. METHODS: We retrospectively analyzed CTEPH patients who underwent a pulmonary function test and respiratory impedance test to evaluate their exertional dyspnea during admission for right heart catheterization from January 2000 to December 2019. We excluded patients with a smoking history to rule out the effect of smoking on obstructive impairment. RESULTS: A total of 135 CTEPH patients were analyzed. The median FEV1.0/FVC was 76.0%, %FEV 1.0 had a negative correlation with the mean pulmonary artery pressure and pulmonary vascular resistance and the CT Angiogram (CTA) obstruction score. A multivariate regression analysis revealed that the CTA obstruction score was an independent factor of a lower %FEV1.0. In the 54 patients who underwent pulmonary endarterectomy, %FEV1.0 was improved in some cases and was not in some. Mean PAP largely decreased after PEA in the better %FEV1.0 improved cases, suggesting that vascular involvement in CTEPH could be associated with spirometry obstructive impairment. CONCLUSION: %FEV1.0 had a significant correlation with the CTA obstruction score. Obstructive impairment might have an etiological relationship with vascular involvement. Further investigations could shed new light on the etiology of CTEPH.

Pulmonary hypertension with a low cardiac index requires a higher PaO2 level to avoid tissue hypoxia.

BACKGROUND AND OBJECTIVE: The optimal oxygen supplementation needed to avoid tissue hypoxia in patients with pulmonary hypertension (PH) remains unclear. This study aimed to identify the arterial oxygen tension (PaO2 ) level needed to avoid tissue hypoxia which results in a poor prognosis in patients with PH. METHODS: We retrospectively analysed the data for 1571 right heart catheterizations in patients suspected of having PH between 1983 and 2017 at our institution. Examinations were classified according to mean pulmonary arterial pressure (mPAP), cardiac index (CI) and the presence of lung disease, pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH). The PaO2 levels needed to avoid tissue hypoxia were compared in each subgroup. RESULTS: The estimated PaO2 equivalent to a mixed venous oxygen tension (PvO2 ) of 35 mm Hg (tissue hypoxia) was 63.2 mm Hg in all patients, 77.0 mm Hg in those with decreased CI (<2.5 L/min/m2 ) and 57.0 mm Hg in those with preserved CI. Multivariate regression analysis identified mPAP, CI and PaO2 to be independent predictors of extremely low PvO2 . Similar results were observed regardless of the severity of PH or the presence of lung disease, PAH or CTEPH. The PaO2 level needed to avoid tissue hypoxia was higher in patients with mild PH and decreased CI than in those with severe PH and preserved CI (70.2 vs 61.5 mm Hg). CONCLUSION: These findings indicate that a decreased CI rather than increased mPAP induces tissue hypoxia in PH. Patients with PH and decreased CI may need adjustment of oxygen therapy at higher PaO2 levels compared with patients with preserved CI.

Long-Term Outcome of Chronic Thromboembolic Pulmonary Hypertension at a Single Japanese Pulmonary Endarterectomy Center.

BACKGROUND: Several new treatments for chronic thromboembolic pulmonary hypertension (CTEPH) have appeared in recent years, which have led to changes in the treatment algorithm. Changes in survival rates and prognostic factors, however, have not been estimated so far.Methods and Results:Two hundred and eighty patients were diagnosed with CTEPH at Chiba University Hospital between June 1986 and June 2016. Survival rate was investigated by date of treatment initiation (group 1, 1986-1998; group 2, 1999-2008; group 3, 2009-2016). Survival rates were also evaluated by treatment strategy: balloon pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and medical treatment. Group 3 had significantly better disease-specific survival than groups 1 and 2 (5-year survival: 91.9% vs. 67.1%, 77.0%, respectively). For the non-PEA (BPA+medication) strategy, group 3 had better disease-specific survival than groups 1 and 2 (5-year survival: 94.9% vs. 54.6%, 74.2%, respectively). The PEA strategy had significantly better survival than the medication strategy in groups 1 and 2, whereas no difference was observed between the BPA, PEA, and medication strategies in group 3. CONCLUSIONS: Survival in CTEPH in the recent era has significantly improved, especially in non-PEA patients. BPA and selective pulmonary vasodilators could improve survival in the non-PEA group. In the present study, no difference in survival was found between PEA and non-PEA.

Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor.

BACKGROUND: Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pulmonary endarterectomy (PEA) specimens. METHODS: We isolated ECs from PEA specimens (CTEPH-ECs) and control EC lines from the intact pulmonary arteries of patients with peripheral lung cancers, using a MACS system. These cells were analyzed in vitro including PCR-array analysis, and the PEA specimens were analyzed with immunohistochemistry. Additionally, the serum HGF levels were determined in CTEPH patients. RESULTS: A three-dimensional culture assay revealed that CTEPH-ECs were highly angiogenic. An angiogenesis-focused gene PCR array revealed a high expression of hepatocyte growth factor (HGF) in CTEPH-ECs. The high expression of HGF was also confirmed in the supernatant extracted from PEA specimens. The immunohistochemical analysis showed expression of HGF on the surface of the thrombus vessels. The serum HGF levels in CTEPH patients were higher than those in pulmonary thromboembolism survivors. CONCLUSION: Our study suggests that there are ECs with pro-angiogenetic character and high expression of HGF in PEA specimens. It remains unknown how these results are attributable to the etiology. However, further investigation focused on the HGF pathway may provide novel diagnostic and therapeutic tools for patients with CTEPH.

Prognostic and pathophysiological marker for patients with chronic thromboembolic pulmonary hypertension: Usefulness of diffusing capacity for carbon monoxide at diagnosis.

BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease in some patients, despite improved treatments. Microvasculopathy has been implicated in the poor outcomes of patients with CTEPH. A reduction in the diffusing capacity for carbon monoxide (DLCO ) was previously suggested to indicate microvasculopathy in CTEPH patients; therefore, we assessed DLCO /alveolar ventilation (DLCO /VA ) as a prognostic and pathophysiological marker in CTEPH. METHODS: We performed a retrospective cohort study of 214 CTEPH patients consecutively diagnosed between 1986 and 2011. After exclusion of 24 patients because of missing DLCO data or severe obstructive impairment, the mortality rates of medically treated patients classified with normal or decreased DLCO values were compared, and prognostic factors were determined. The relationship between long-term surgical outcomes and DLCO /VA was also investigated. RESULTS: Ninety-one inoperable patients were treated medically, two of whom underwent balloon pulmonary angioplasty. Ninety-nine underwent pulmonary endarterectomy. The 5-year survival rate of medically treated patients was significantly lower in patients with decreased DLCO /VA than in those with normal values (61.4% vs 90.4%, P = 0.017). Decreased preoperative DLCO /VA was associated with a smaller percent decrease in post-operative pulmonary vascular resistance, but not with the extent of proximal thrombi; these results may support our hypothesis that DLCO reflects microvascular involvement. CONCLUSION: Decreased DLCO /VA was associated with poor outcomes of medically treated CTEPH patients; and may be useful for identifying high-risk patients, potentially leading to earlier and more appropriate interventions.

Coagulation-Fibrinolysis System and Postoperative Outcomes of Patients With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The postoperative changes in the coagulation-fibrinolysis system and the association between the system and postoperative course of patients with chronic thromboembolic pulmonary hypertension (CTEPH) who have undergone pulmonary endarterectomy (PEA) remain unclear. METHODS AND RESULTS: Between 1986 and 2013, 117 patients (55.1±11.2 years, preoperative mean pulmonary arterial pressure 46.5±10.5 mmHg) underwent PEA, and 15 patients died during the perioperative period. We studied the association between the preoperative coagulation-fibrinolysis markers and surgical outcomes of all patients, and the long-term outcomes of the 102 survivors from the date of PEA. We also investigated the postoperative changes in coagulation-fibrinolysis markers and their association with residual pulmonary hypertension (PH) in 20 consecutive patients. Only an elevated factor VIII level was associated with perioperative death. Thrombomodulin and plasminogen values were significantly increased after PEA. Univariate logistic regression analysis revealed that D-dimer positivity at follow-up was a risk factor for residual PH. Patients with both an elevated fibrinogen level (≥291 mg/dl [median]) and decreased plasminogen activity (<100% [median]) had significantly worse disease-specific survival than the other patients (5-year disease-specific survival: 84.0% vs. 100%, respectively; P=0.0041 [log-rank test]). CONCLUSIONS: Preoperatively high fibrinogen and low plasminogen values in patients with CTEPH are associated with poor long-term postoperative outcome. PEA benefited not only the pulmonary hemodynamics but also the coagulation-fibrinolysis system of patients.

Mean Pulmonary Artery Pressure Using Echocardiography in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Mean pulmonary arterial pressure (MPAP) is an important pulmonary hemodynamic parameter used in the management of patients with chronic thromboembolic pulmonary hypertension (CTEPH). We compared echocardiography-derived estimates of MPAP with right heart catheterization (RHC) to identify reliable noninvasive methods of estimating MPAP-derived RHC (MPAPRHC) in these patients. METHODS AND RESULTS: Echocardiography and RHC were performed in 56 patients with CTEPH (60.5±12.0 years; 44 females). We measured the tricuspid regurgitation (TR) pressure gradient (TRPG) using echocardiography. The mean systolic right ventricular (RV)-right atrial (RA) gradient was calculated by tracing the TR time velocity flow. Systolic and mean pulmonary artery pressures (SPAPTRand MPAPTR) estimated from TRPG and mean systolic RV-RA gradient were calculated by adding RA pressure based on the inferior vena cava. MPAPChemlawas calculated using Chemla's formula: 0.61×SPAPTR+2 mmHg. MPAPRHCand pulmonary vascular resistance were 35.9±11.3 mmHg and 6.6±3.6 Wood units, respectively. The mean difference from MPAPRHCand limits of agreement were -1.5 mmHg and -19.6 to 16.5 mmHg for MPAPTR, and -4.6 mmHg and -24.5 to 15.2 mmHg for MPAPChemla. Accuracy within 10 mmHg and 5 mmHg of MPAPRHCwas 80.4% and 46.4% for MPAPTR, and 71.4% and 48.2% for MPAPChemla, respectively. CONCLUSIONS: MPAPTRand MPAPChemlaare reliable estimates for MPAPRHCin patients with CTEPH. (Circ J 2016; 80: 1259-1264).

Synergistic Effects of ACE Insertion/Deletion and GNB3 C825T Polymorphisms on the Efficacy of PDE-5 Inhibitor in Patients with Pulmonary Hypertension.

BACKGROUND: The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the C825T polymorphism in the G-protein ß3 subunit gene (GNB3) are associated with the efficacy of phosphodiesterase-5 inhibitor (PDE-5I) in erectile dysfunction. In addition, GNB3 genotypes could be associated with clinical worsening in pulmonary hypertension (PH) treated with PDE-5I. However, no studies have described the synergistic effects of gene polymorphisms on drug efficacy in patients with PH. OBJECTIVES: We aimed to examine the effects of combined ACE/GNB3 polymorphisms on the efficacy of PDE-5I in patients with PH. METHODS: This was a retrospective uncontrolled study. Ninety patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) were treated with PDE-5I. Freedom from clinical worsening and pre- and post-treatment parameters, including the 6-min walk distance (6MWD) and serum brain natriuretic peptide (BNP) levels, were compared between patients with ACE/GNB3 II/TT and non-II/TT genotypes. RESULTS: Time to clinical worsening was significantly longer in patients with the II/TT genotype than in those with the non-II/TT genotype (5-year freedom from clinical worsening: 100 vs. 48.8%, respectively; p = 0.018), even in patients with CTEPH alone. Post-treatment 6MWD and BNP levels in patients with the II/TT genotype tended to be better than those in patients with the non-II/TT genotype. The ACE/GNB3 genotype was a significant predictor of clinical worsening, even after adjusting for pulmonary vascular resistance and 6MWD. CONCLUSIONS: ACE and GNB3 polymorphisms may synergistically influence the efficacy of PDE-5I in patients with PH.

Effects of Surgical and Medical Treatment on Quality of Life for Patients With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: This study aimed to investigate the predictors of quality of life (QOL) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), changes in QOL after surgical and medical treatments, and the relationship between baseline QOL and survival. METHODS AND RESULTS: QOL was measured in 128 patients with CTEPH (male/female: 42/86, age: 56±12 years, surgical/medical: 65/63) using the Short-Form 36 (SF-36) questionnaire. Multiple regression analysis showed pulmonary vascular resistance (PVR) and 6-min walking distance (6MWD) were associated with physical functioning (PF) (P<0.01) and physical component summary (PCS) (P<0.01). In the surgical group, 7 subscales and 2 summary scores improved significantly, and in the medical group 6 subscales and the mental component summary, although the change in QOL was greater in the surgical group. The patients in the conventional therapy group with higher PF had significantly better survival than those with lower PF (5-years survival: 89.5% vs. 50.8%, P=0.002). This difference in survival was not observed in the group receiving pulmonary arterial hypertension (PAH)-specific therapy (100% vs. 100%, P=0.746). CONCLUSIONS: PVR and 6MWD were associated with PF or PCS in CTEPH patients. QOL improved after surgical or medical therapy, with a greater change in the surgical group. PAH-specific therapy improved survival in patients with lower PF at diagnosis.

Effect of threshold on the correlation between airflow obstruction and low attenuation volume in smokers assessed by inspiratory and expiratory MDCT.

BACKGROUND: The estimation of emphysematous changes is very sensitive to computed tomography (CT) threshold level. In clinical practice, the predetermined threshold is usually set at -950 Hounsfield units (HU) for the detection of low attenuation volume (LAV). However, threshold levels that are tightly connected to pulmonary function abnormalities have not been determined. PURPOSE: To determine the threshold level for calculating an LAV that closely reflects airflow limitation in patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Seventy-six consecutive non-COPD smokers and COPD patients underwent paired inspiratory and expiratory multidetector CT (MDCT). LAV% was segmented every 10 HU between -1000 and -750 HU to examine the correlation between LAV% and indexes of obstructive impairment. RESULTS: LAV% gradually increased as the threshold level increased on both inspiratory and expiratory images. LAV% on inspiratory images was higher than that on expiratory images at all threshold levels between -1000 and -750 HU. The threshold level that correlated with obstructive impairment differed between the two images: -930 HU on inspiratory and -870 or -880 HU on expiratory images. CONCLUSION: LAV% dramatically changed according to the threshold level on both inspiratory and expiratory images, indicating that LAV% is dependent on the attenuation threshold level in patients with COPD. The threshold linking LAV% to airflow limitation was higher on expiratory than on inspiratory images.

Association of plasma fibrinogen and plasminogen with prognosis of inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: It is unclear whether abnormalities of coagulation or fibrinolysis are associated with disease progression of chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to investigate the association of these factors with the severity and prognosis of CTEPH. METHODS AND RESULTS: Between 1986 and 2011, plasma fibrinogen and plasminogen were measured in 89 of 106 consecutive patients with inoperable CTEPH (17 men; mean age, 55.9±14.1 years old; mean pulmonary arterial pressure, 44.0±12.4 mmHg) and the association of level with severity and prognosis were also examined. Seventeen patients had high fibrinogen and low plasminogen (medians, ≥291 mg/dl and <101%, respectively). These patients had significantly lower cardiac index (2.26±0.68 vs. 2.70±0.57 L·min(-1)·m(-2), P=0.007), higher pulmonary vascular resistance (PVR; 13.29±7.54 vs. 9.15±4.14 Wood units, P=0.003), and poor survival (5-year survival, 35.3% vs. 88.0%, P<0.001) compared to the other 72 patients. Additional analysis showed significantly poor survival in these patients compared with the other patients who did not have modern therapy. On multivariate analysis plasma fibrinogen, plasminogen and PVR were independent predictors of survival in medically treated patients. CONCLUSIONS: High plasma fibrinogen and low plasminogen are associated with poor survival in CTEPH patients without modern therapy.

A 65-Year-Old Man with Refractory Hemoptysis Associated with Chronic Progressive Pulmonary Aspergillosis Who Failed to Respond to Combined Endobronchial Occlusion and Bronchial Artery Embolization: A Case Report and Literature Review.

BACKGROUND Hemoptysis due to airway hemorrhage is treated with hemostatic agents, bronchial artery embolization (BAE), or surgical resection. We present the case of a 65-year-old man with refractory hemoptysis associated with chronic progressive pulmonary aspergillosis (CPPA) who failed to respond to combined endobronchial occlusion (EBO) with endobronchial Watanabe spigot (EWS) and BAE. CASE REPORT A 63-year-old man was diagnosed with CPPA in the right upper lung and presented to our hospital 2 years later for hemoptysis at age 65. He developed severe hemoptysis during an outpatient visit, and was urgently admitted, intubated, and ventilated to prevent choking on blood clots. Chest computed tomography showed a large mass in the apical portion of the right lung, constituting apical pleural thickening and an encapsulated pleural effusion, and dilatation in the bronchial artery supplying the right upper lung lobe. Bronchoscopy revealed the right upper lobe B1-B3 as the bleeding source. The patient had recurrent hemoptysis that was not controlled by BAE or 6 EBO+EWS procedures, and he ultimately died of hypoxemia.In the literature review, EBO+EWS can effectively control hemoptysis in appropriate cases, without the need for BAE or surgical lung resection. It is less invasive, is associated with fewer adverse events than BAE or surgery, and can achieve temporary hemostasis for severe hemoptysis. CONCLUSIONS BAE and EBO+EWS were ineffective in controlling recurrent hemoptysis caused by CPPA in this case. However, a multidisciplinary approach such as attempting hemostasis with combined EBO+EWS and BAE may be a viable treatment option in severe cases of hemoptysis.

Aorta and main pulmonary artery segmentation using stacked U-Net and localization on non-contrast-enhanced computed tomography images.

BACKGROUND: The contact between the aorta, main pulmonary artery (MPA), main pulmonary vein, vena cava (VC), and esophagus affects segmentation of the aorta and MPA in non-contrast-enhanced computed tomography (NCE-CT) images. PURPOSE: A two-stage stacked U-Net and localization of the aorta and MPA were developed for the segmentation of the aorta and MPA in NCE-CT images. METHODS: Normal-dose NCE-CT images of 24 subjects with chronic thromboembolic pulmonary hypertension (CTEPH) and low-dose NCE-CT images of 100 subjects without CTEPH were used in this study. The aorta is in contact with the ascending aorta (AA) and MPA, the AA with the VC, the aortic arch (AR) with the VC and esophagus, and the descending aorta (DA) with the esophagus. These contact surfaces were manually annotated. The contact surfaces were quantified using the contact surface ratio (CSR). Segmentation of the aorta and MPA in NCE-CT images was performed by localization of the aorta and MPA and a two-stage stacked U-Net. Localization was performed by extracting and processing the trachea and main bronchus. The first stage of the stacked U-Net consisted of a 2D U-Net, 2D U-Net with a pre-trained VGG-16 encoder, and 2D attention U-Net. The second stage consisted of a 3D U-Net with four input channels: the CT volume and three segmentation results of the first stage. The model was trained and tested using 10-fold cross-validation. Segmentation of the entire volume was evaluated using the Dice similarity coefficient (DSC). Segmentation of the contact area was also assessed using the mean surface distance (MSD). The statistical analysis of the evaluation underwent a multi-comparison correction. CTEPH and non-CTEPH cases were classified based on the vessel diameters measured from the segmented MPA. RESULTS: For the noncontact surfaces of AA, the MSD of stacked U-Net was 0.31 ± 0.10 mm (p < 0.05) and 0.32 ± 0.13 mm (p < 0.05) for non-CTEPH and CTEPH cases, respectively. For contact surfaces with a CSR of 0.4 or greater in AA, the MSD was 0.52 ± 0.23 mm (p < 0.05), and 0.68 ± 0.29 mm (p > 0.05) for non-CTEPH and CTEPH cases, respectively. MSDs were lower than those of 2D and 3D U-Nets for contact and noncontact surfaces; moreover, MSDs increased slightly with larger CSRs. However, the stacked U-Net achieved MSDs of approximately 1 pixel for a wide contact surface. The area under the receiver operating characteristic curve for CTEPH and non-CTEPH classification using the right main pulmonary artery (RMPA) diameter was 0.97 (95% confidence interval [CI]: 0.94-1.00). CONCLUSIONS: Segmentation of the aorta and MPA on NCE-CT images were affected by vascular and esophageal contact. The application of stacked U-Net and localization techniques for non-CTEPH and CTEPH cases mitigated the impact of contact, suggesting its potential for diagnosing CTEPH.

Improved survival in medically treated chronic thromboembolic pulmonary hypertension.

BACKGROUND: The surgical indication for chronic thromboembolic pulmonary hypertension (CTEPH) has been modified due to recognition of peripheral type CTEPH and changes in surgical methods and skill. Bosentan and sildenafil are used as modern oral therapy (mod Tx) in patients with inoperable CTEPH, although it remains unknown whether they have positive effects on survival. METHODS AND RESULTS: A total of 202 patients were diagnosed with CTEPH at Chiba University Hospital between 1986 and 2010, 100 of whom underwent pulmonary endarterectomy. Seven medically treated patients with pulmonary vascular resistance (PVR) ≤ 300 dyn·s·cm(-5) were regarded as having mild disease. Survival rate was stratified by date of diagnosis (group 1, 1986-1998; group 2, 1999-2004; group 3, 2005-2010), and prognostic factors in the remaining 95 medically treated patients were investigated. Group 3 included the most patients treated with mod Tx (group 1, 9.1%; group 2, 24.2%; group 3, 65.0%) and had significantly better survival than either group 1 or 2 (5-year survival: group 1, 54.6%; group 2, 69.7%; group 3, 87.3%). Patients receiving mod Tx had significantly better survival than those not on mod Tx (5-year survival: 88.9% vs. 60.2%). Multivariate analysis showed that mod Tx, lower PVR, and lack of comorbidity were significant predictors of better outcome. CONCLUSIONS: Medically treated patients with CTEPH had a better survival rate, and the use of mod Tx contributed to improved survival.