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.

Mixed venous oxygen tension is a crucial prognostic factor in pulmonary hypertension: a retrospective cohort study.

BACKGROUND: The prognostic value of mixed venous oxygen tension (PvO2) at pulmonary hypertension diagnosis treated with selective pulmonary vasodilators remains unclear. This study sought to investigate the association of PvO2 with long-term prognosis in pulmonary arterial hypertension (PAH) and medically treated chronic thromboembolic pulmonary hypertension (CTEPH) and to identify the distinct mechanisms influencing tissue hypoxia in patients with CTEPH or PAH. METHODS: We retrospectively analyzed data from 138 (age: 50.2 ± 16.6 years, 81.9% women) and 268 (age: 57.4 ± 13.1 years, 72.8% women) patients with PAH and CTEPH, respectively, diagnosed at our institution from 1983 to 2018. We analyzed the survival rates of patients with/without tissue hypoxia (PvO2 < 35 mmHg) and identified their prognostic factors based on the pulmonary hypertension risk stratification guidelines. RESULTS: Survival was significantly poorer in patients with tissue hypoxia than in those without it for PAH (P = 0.001) and CTEPH (P = 0.017) treated with selective pulmonary vasodilators. In patients with PAH, PvO2 more strongly correlated with prognosis than other hemodynamic prognostic factors regardless of selective pulmonary vasodilators usage. PvO2 was the only significant prognostic factor in patients with CTEPH treated with pulmonary hypertension medication. Patients with CTEPH experiencing tissue hypoxia exhibited significantly poorer survival than those in the intervention group (P < 0.001). PvO2 more strongly correlated with the cardiac index (CI) than the alveolar-arterial oxygen gradient (A-aDO2) in PAH; whereas in CTEPH, PvO2 was more strongly correlated with A-aDO2 than with CI. CONCLUSIONS: PvO2 may represent a crucial prognostic factor for pulmonary hypertension. The prognostic impact of tissue hypoxia affects different aspects of PAH and CTEPH, thereby reflecting their distinct pathogenesis.

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.

Inversion of the Axial Information during Oxidative Aromatization in the Synthesis of Axially Chiral Biaryls with Organocatalysis as a Key Step.

Invited for the cover of this issue is the group of Yujiro Hayashi at the University of Tohoku University. The image depicts the spinning motion of a figure skater, which illustrates the transformation of the chiral information investigated in this work. Read the full text of the article at 10.1002/chem.201905814.

Inversion of the Axial Information during Oxidative Aromatization in the Synthesis of Axially Chiral Biaryls with Organocatalysis as a Key Step.

The pot-economical, highly enantioselective synthesis of axially chiral biaryls was developed by using one-pot organocatalyst-mediated domino and aromatization reactions as key steps. The axial information of the precursor, which also has central chirality, was completely inverted in the final biaryls. The inversion of the axial information occurred in the conversion of the central chirality to the axial chirality of an oxidative aromatization step.

Successful pulmonary embolectomy with central extra-corporeal membranous oxygenation for acute pulmonary thromboembolism.

The treatment of acute pulmonary thromboembolism with a hemorrhagic condition is quite challenging and it usually presents a clinical dilemma. Pulmonary embolectomy is generally performed with cardiopulmonary bypass; however, cardiopulmonary bypass usually requires full anticoagulation which cannot be used for patients with a hemorrhagic condition. We herein report a successful case of pulmonary embolectomy that was accomplished using central veno-arterial extracorporeal membranous oxygenation, instead of cardiopulmonary bypass, for a patient with an acute fatal pulmonary thromboembolism and hemorrhagic cerebral infarction following lung cancer surgery. Our strategy consists of surgical embolectomy under central veno-arterial extracorporeal membranous oxygenation with partial anticoagulation and the placement of an inferior vena cava filter to prevent recurrence without the use of anticoagulation therapy.

Asymmetric Synthesis of Biaryl Atropisomers Using an Organocatalyst-Mediated Domino Reaction as the Key Step.

A three-pot synthetic method that features the use of an organocatalyst as the key step was developed for the preparation of biaryl atropisomers. The first reaction is an asymmetric domino Michael-Henry reaction catalyzed by diphenylprolinol silyl ether to afford the substituted nitrocyclohexanecarbaldehyde with four stereogenic centers and one defined configuration of a stereogenic axis with excellent enantioselectivity. Removal of the central chirality from the domino products afforded biaryl atropisomers having axial chirality with excellent enantioselectivity.

Pluripotent Features of Doubly Thiophene-Fused Benzodiphospholes as Organic Functional Materials.

Linear ladder-type π-conjugated molecules have attracted much interest because of their intriguing physicochemical properties. To modulate their electronic structures, an effective strategy is to incorporate main-group elements into ladder-type π-conjugated molecules. In line with this strategy, a variety of ladder-type π-conjugated molecules with main-group elements have been synthesized to explore their potential utility as organic functional materials. In this context, phosphole-based π-conjugated molecules are highly attractive, owing to their unique optical and electrochemical properties, which arise from the phosphorus atom. Herein, the synthesis and physicochemical properties of doubly thiophene-fused benzodiphospholes, as a new class of phosphole-based ladder-type π-conjugated molecule, are reported. Systematic investigations into the physicochemical properties of doubly thiophene-fused benzodiphospholes revealed their pluripotent features: intense near-infrared fluorescence, excellent two-photon absorption property, and remarkably high electron-transporting ability. This study demonstrates the potential utility of doubly thiophene-fused benzodiphospholes as organic functional materials for biological imaging, nonlinear optics, organic transistors, and organic photovoltaics.

Phosphole-Thiophene Hybrid: A Dual Role of Dithieno[3,4- b:3',4'- d]phosphole as Electron Acceptor and Electron Donor.

We have synthesized dithieno[3,4- b:3',4'- d]phosphole derivatives as a new type of thiophene-fused phospholes. These dithienophospholes were found to show intramolecular charge transfer interactions by introducing electron-donating or -withdrawing groups on the peripheral aryl groups. Namely, they exhibit the unique hybrid character of electron-withdrawing phosphole and electron-donating thiophene.

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.

Is ganglionated plexus ablation effective for treating atrial fibrillation?

PURPOSE: Very few studies have investigated the efficacy of ganglionated plexus ablation during the conventional maze procedure. In this study, we sought to evaluate its additive effect in reducing recurrent atrial fibrillation after concomitant maze surgery. METHODS: A retrospective study was conducted of 79 patients who underwent Cox maze IV concomitantly with open-heart surgery with (GP group) or without (Maze group) ganglionated plexus mapping. All active ganglionated plexuses were ablated. The two groups were compared and their follow-up data were analyzed. RESULTS: Active ganglionated plexuses were found in 81% of patients who underwent ganglionated plexus mapping. The rates of freedom from atrial fibrillation at 1 year in the GP and Maze groups were 77 and 75%, respectively. The cumulative freedom from atrial fibrillation at follow-up (27.7 ± 17.3 months) was comparable in the two groups (p = 0.427). A multivariate analysis revealed that persistent atrial fibrillation for more than 90 months was an independent predictor of recurrent atrial fibrillation. CONCLUSION: Ganglionated plexus ablation with Cox maze IV did not reduce the incidence of recurrent atrial fibrillation in comparison to Maze alone.

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.

Change of luminal diameter of skeletonized and non-skeletonized radial artery graft at early and late postoperative period.

The radial artery is increasingly used as a second arterial conduit for myocardial revascularization. However, the radial artery is susceptible to vasospasm, which is thought to be the principal cause of graft failure. The radial artery is harvested as a skeletonized or a non-skeletonized graft, but the effect of different harvesting technique remains unknown. In this study, we compared the early- and mid-term angiographic findings to elucidate its influence on the graft luminal diameter. We harvested 39 radial arteries either as a skeletonized (n = 18) or a non-skeletonized graft (n = 21) using an ultrasonic scalpel. We constructed a composite straight graft by combining a right internal thoracic artery and a radial artery. All the radial artery grafts were sequentially anastomosed to coronary arteries. We measured the diameters of the radial arteries before the operation, within 1 month and 1 year after the operation. At early postoperative period, graft diameter was significantly larger in skeletonized grafts. Graft diameter at the point before the first and the second anastomosis was similar in skeletonized grafts, although that was significantly smaller before the second anastomosis in non-skeletonized grafts. However, 1 year after the operation, the graft diameter was comparable and equally reduced after the first anastomosis in both groups. Skeletonization with an ultrasonic scalpel increases the luminal diameter of the radial artery graft at early postoperative period, which, however, reduces possibly as adaptation to graft flow 1 year after the operation.

Analysis of anatomical risk factors for persistent type II endoleaks following endovascular abdominal aortic aneurysm repair using CT angiography.

PURPOSE: To predict persistent type II endoleaks (pT2Es) following endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms, we examined factors related to post-EVAR pT2Es. METHODS: Eighty-four cases of EVAR were analyzed. T2Es that persisted for ≥6 months were defined as pT2Es. pT2Es flowing from an inferior mesenteric artery (IMA) and lumbar artery (LA) were termed pIMA-T2Es and pLA-T2Es, respectively. The anatomical factors concerning the aneurysm, IMA and LAs were assessed in the preoperative CT angiography images. A statistical analysis was performed on the factors associated with pT2Es. RESULTS: The incidence of pT2Es was 25 %. pT2Es were associated with postoperative changes in the aneurysm diameter. A univariate analysis showed that a sac thrombus and the number of patent side branches arising from an aneurysm were significant factors associated with pT2Es. The IMA diameters were significantly larger in cases of pIMA-T2Es. The significant factors associated with pLA-T2Es were a circumferential thrombus, the number of patent LAs and the mean LA diameter. Multivariate analyses indicated that a circumferential thrombus was a protective factor for pT2Es, whereas an IMA ≥2.6 mm and each additional LA branch ≥1.9 mm were powerful risk factors for a pT2E. CONCLUSION: Significant anatomical factors associated with pT2E were found in this study. These factors may be useful in selecting patients for perioperative intervention.

Staged hybrid repair for a patient with chronic type B aortic dissection.

Vascular prosthesis replacement and thoracic endovascular repair (TEVAR) are used to treat patients with enlarged chronic type B aortic dissection. A case in which thrombosis of the false lumen was achieved by the staged combination of these two methods is presented. A 41-year-old woman with a thoracoabdominal aortic aneurysm (maximum short diameter 44 mm) identified 5 years earlier was being monitored as an outpatient in our department when she presented with back pain. Computed tomography (CT) showed acute type B aortic dissection (DeBakey type IIIa), which was managed conservatively. When CT showed an aortic dissection with a patent false lumen immediately below the left subclavian artery bifurcation, one-debranching TEVAR was performed to close the entry, along with right axillary artery to left axillary artery bypass surgery. Outpatient CT at 3 months postoperatively showed rapid enlargement in the vicinity of the celiac artery. Thoracoabdominal aortic replacement to prevent rupture was performed, and the patient was then monitored as an outpatient. CT at age 43 years showed enlargement of the residual false lumen. Additional TEVAR was successfully performed. Thus, three-stage treatment was conducted to enlarge the residual false lumen, causing successful thrombosis of the false lumen.

Endovascular aneurysm repair with mesenteric artery bypass for abdominal aortic aneurysm with occlusion of celiac and superior mesenteric arteries.

A 67-year-old male patient required surgical management of an abdominal aortic aneurysm. Contrast-enhanced computed tomography showed a saccular infrarenal abdominal aortic aneurysm and occlusion of the origins of the celiac artery, superior mesenteric artery, and inferior mesenteric artery. Aortography revealed large amounts of blood flow from capillaries around the abdominal aorta to the inferior mesenteric artery and retrograde blood flow to a meandering mesenteric artery through the superior rectal artery. Considering the risk of bowel ischemia, we performed endovascular aneurysm repair with mesenteric artery bypass. The operation was successful, and his postoperative course was uneventful. This procedure could be useful and less invasive.

Different prognostic outcomes in two cases of FDG-PET/CT-Positive and -negative cardiac angiosarcoma.

Cardiac angiosarcoma is a rare malignant tumor with a poor prognosis, characterized by the high uptake of 18F-fluorodeoxyglucose (FDG). This case report presents two cases of cardiac angiosarcoma with a marked difference in FDG uptake and prognosis.Case Summary:Case 1: A 40-year-old male presented with syncope. Ultrasound echocardiography demonstrated a cardiac tumor with a high uptake of 18F-FDG (maximum standardized uptake value=9.2). The patient underwent heart catheterization and tumor biopsy. The pathological result was high-grade angiosarcoma, and the MIB-1(Ki-67) proliferation index was approximately 20%. Systemic chemotherapy was administered; however, the patient died 2 years and 5 months after disease onset.Case 2: A 65-year-old female had a right atrial tumor incidentally diagnosed during routine ultrasound echocardiography. The tumor exhibited a low uptake of 18F-FDG (maximum standardized uptake value=1.8). Open heart surgery was performed, and the tumor was completely resected. Histological analysis revealed low-grade angiosarcoma, and the MIB-1(Ki-67) proliferation index was less than 5%. The patient was followed-up and had not relapsed 2 years after surgery.Conclusion: 18F-FDG uptake may reflect pathological tumor grade and prognosis in cardiac angiosarcoma.

Clinical significance of lung cross-sectional area measured by computed tomography in chronic thromboembolic pulmonary hypertension: The correlation with pulmonary hemodynamics and the limitations.

The percentage cross-sectional area of the lung under five (%CSA<5) is the percentage of pulmonary vessels with <5 mm2 area relative to the total lung area on computed tomography (CT). The extent that %CSA<5 is related to pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is unclear, as is the effect of pulmonary endarterectomy (PEA) on %CSA<5. Therefore, we aimed to evaluate the clinical significance of %CSA<5 in patients with CTEPH. We studied 98 patients (64 females, mean age 62.5 ± 11.9 years), who underwent CT with %CSA<5 measurement and right heart catheterization (RHC). Patients were classified into groups based on eligibility for PEA. We compared the %CSA<5 with pulmonary hemodynamics measured by RHC in various groups. In 38 patients who underwent PEA, the relationship between %CSA<5 and pulmonary hemodynamics was also evaluated before and after PEA. Significant correlations between %CSA<5 and pulmonary vascular resistance, and compliance, and pulmonary artery pulse pressure were observed in all patients. Pulmonary hemodynamics in the patients who underwent or were eligible for PEA showed a significant correlation with %CSA<5. Additionally, %CSA<5 was significantly lower in the postoperative than in the preoperative group. There was no correlation between changes in %CSA<5 and pulmonary hemodynamics before and after PEA. Furthermore, %CSA<5 did not correlate significantly with prognosis. %CSA<5 may reflect pulmonary hemodynamics in CTEPH with central thrombosis. Furthermore, %CSA<5 was reduced by PEA postoperatively. However, %CSA<5 is not a prognostic indicator, its clinical usefulness in CTEPH patients is limited, and further validation is required.