Progression from normal vessel wall to atherosclerotic plaque: lessons from an optical coherence tomography study with follow-up of over 5 years.

The initial process of atherosclerotic development has not been systematically evaluated. This study aimed to observe atherosclerotic progression from normal vessel wall (NVW) to atherosclerotic plaque and examine local factors associated with such progression using > 5-year long-term follow-up data obtained by serial optical coherence tomography (OCT). A total of 49 patients who underwent serial OCT for lesions with NVW over 5 years (average: 6.9 years) were enrolled. NVW was defined as a vessel wall with an OCT-detectable three-layer structure and intimal thickness ≤ 300 µm. Baseline and follow-up OCT images were matched, and OCT cross sections with NVW > 30° were enrolled. Cross sections were diagnosed as "progression" when the NVW in these cross sections was reduced by > 30° at > 5-year follow-up. Atherogenic progression from NVW to atherosclerotic plaque was observed in 40.8% of enrolled cross sections. The incidence of microchannels in an adjacent atherosclerotic plaque within the same cross section (6.7 vs. 3.3%; p = 0.046) and eccentric distribution of atherosclerotic plaque (25.0 vs. 12.6%; p < 0.001) at baseline was significantly higher in cross sections with progression than in those without. Cross sections with progression exhibited significantly higher NVW intimal thickness at baseline than cross sections without progression (200.1 ± 53.7 vs. 180.2 ± 59.6 µm; p < 0.001). Multivariate analysis revealed that the presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness at baseline were independently associated with progression at follow-up. The presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness were potentially associated with initial atherosclerotic development from NVW to atherosclerotic plaque.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Efficacy and Safety of Balloon Pulmonary Angioplasty for Patients With Chronic Thromboembolic Pulmonary Hypertension and Comorbid Chronic Obstructive Pulmonary Disease.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.

RC time (resistance × compliance) is related to residual symptom after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

Background: Right ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time. Methods: We reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms. Results: RC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p < 0.001). Residual symptom after PEA of Decrease group were significantly better than that of Non-decrease group in RC time (12 patients, 40% vs. 11 patients, 78.6%, p < 0.02). Furthermore, multivariate analysis revealed that only RC time after PEA was independently associated with residual symptom (OR 1.026, 95% CI 1.005-1.048; p = 0.017). Conclusions: RC time was decreased after PEA, and might be a possible indicator for predicting PEA success.

Microvasculopathy Evaluated by Dual-Energy Computed Tomography in Patients with Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

Background: Poor subpleural perfusion (PSP) on dual-energy computed tomography (DE-CT) suggests microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH). However, whether the microvasculopathy findings are equivalent to those in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to elucidate the characteristics of microvasculopathy in CTEPH compared to those of that in PAH. Methods: We retrospectively reviewed subpleural perfusion on DE-CT and the hemodynamics of 23 patients with PAH and 113 with inoperable CTEPH. Subpleural perfusion on DE-CT was classified as poor (subpleural spaces in all segments with little or no perfusion) or normal. Results: PSP was observed in 51% of patients with CTEPH and in 4% of those with PAH (p < 0.01). CTEPH patients with PSP had poorer baseline hemodynamics and lower diffusing capacity for carbon monoxide divided by the alveolar volume (DLCO/VA) than those with CTEPH with normal perfusion (pulmonary vascular resistance [PVR]: 768 ± 445 dynes-sec/cm5 vs. 463 ± 284 dynes-sec/cm5, p < 0.01; DLCO/VA, 60.4 ± 16.8% vs. 75.9 ± 15.7%, p < 0.001). Despite the existence of PSP, hemodynamics improved to nearly normal in both groups after balloon pulmonary angioplasty. Conclusions: PSP on DE-CT, which is one of the specific imaging findings in CTEPH, might suggest a different mechanism of microvasculopathy from that in PAH.

Assessment of oxygenation after balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: The efficacy of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension would be promising. However, some patients showed residual dyspnea or symptoms, despite normalized hemodynamics. We aimed to clarify the clinical impact of oxygenation parameters on BPA outcome. METHOD: Ninety-nine consecutive patients who underwent BPA from September 2011 to December 2019 were enrolled. We evaluated hemodynamics with right heart catheterization, arterial blood gas examination, New York Heart Association functional class (NYHA-FC), respiratory function tests, nocturnal oximetry, and exercise capacity (6-min walk test and cardiopulmonary exercise testing) at baseline and after BPA. RESULT: Nearly normal hemodynamics was achieved after BPA (mean pulmonary artery pressure (PAP): 37.5 ± 10.0 to 20.6 ± 4.9 mmHg, p < 0.01). Oxygenation slightly improved (partial pressure of arterial oxygen; 61.5 ± 12.3 to 67.7 ± 12.7 mmHg, p < 0.01). Exertional desaturation remained unchanged (-8.1 ± 4.8 to -7.8 ± 5.1, p = 0.59), and this was associated with residual symptom (NYHA-FC ≥ 2) after BPA (OR 0.591, 95% CI 0.416-0.840, p = 0.003) in multivariate regression analyses. Lower vital capacity (r2 = 0.03, p = 0.01), higher mean PAP (r2 = 0.08, p = 0.02), and higher minute ventilation/carbon dioxide production (VE/VCO2) slope (r2 = 0.18, p < 0.01), the marker of ventilatory inefficiency, were correlated with exertional desaturation after BPA in multivariate linear analyses. CONCLUSION: Although hemodynamics nearly normalized, oxygenation did not. Moreover, exertional desaturation remained unchanged. This might cause residual symptom after BPA. Residual pulmonary hypertension suggesting incurable arteriopathy, and higher VE/VCO2 slope suggesting ventilation-perfusion mismatch might be related to exertional desaturation. Domiciliary oxygen therapy should be continued, if necessary.

The role of balloon pulmonary angioplasty and pulmonary endarterectomy: Is chronic thromboembolic pulmonary hypertension still a life-threatening disease?

BACKGROUND: The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched the BPA program in 2011. The aim was to analyze the survival and treatment efficacy of our CTEPH treatment program in the modern management era. METHODS AND RESULTS: We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed from January 2011 (i.e. after the availability of BPA) to December 2019. Of forty-one patients who underwent pulmonary endarterectomy (PEA), 25 underwent additional BPA (Combination group) and the others were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group). The remaining 12 patients did not undergo any interventional treatments. The 1- and 5-year survival rates of operated patients (n = 41) were 97.4% and 90.0%, compared to 96.9% and 86.9% in not-operated patients (n = 102), respectively (p = 0.579). There was no mortality in the Combination group. Mean pulmonary artery pressure after treatments in the PEA only, Combination, and BPA only groups was 20.5 ± 6.7, 17.9 ± 4.9, and 20.7 ± 4.6 mmHg, respectively (p = 0.067, one-way ANOVA). Percent decrease of pulmonary vascular resistance in each treatment groups was -73.7 ± 11.3%, -74.3 ± 11.8%, and - 54.9 ± 22.5%, respectively (p < 0.01, one-way ANOVA). CONCLUSION: There was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.

Evaluation of microvasculopathy using dual-energy computed tomography in patients with chronic thromboembolic pulmonary hypertension.

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused (n = 49) or normally perfused group (n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score-0.793, R2 = 0.225, p < 0.01), but lung perfusion of blood volume score in poorly perfused group was not. Poorly perfused group had higher pulmonary vascular resistance (879 ± 409 dynes-s/cm5 vs. 574 ± 279 dynes-s/cm5, p < 0.01) and lower lung perfusion of blood volume score (22.1 ± 5.4 vs. 26.4 ± 6.6, p < 0.01) and % diffusing capacity for carbon monoxide divided by the alveolar volume (59.9 ± 15.4% vs. 78.8 ± 14.2%, p < 0.01). Perfusion of blood volume score in the normally perfused group showed an inverse correlation with pulmonary vascular resistance; however, that in poorly perfused group did not. Microvasculopathy might contribute to severe hemodynamics, apart from pulmonary vascular obstruction. In our experience, more than half of treatment-naïve chronic thromboembolic pulmonary hypertension patients have microvasculopathy.

Open-label multicenter registry on the outcomes of peripheral arterial disease treated by balloon angioplasty with optical frequency domain imaging in superficial femoral artery and popliteal artery (OCEAN-SFA study).

Although balloon angioplasty for femoropopliteal artery lesions has been associated with restenosis rates of up to 60% at 12 months, the mechanism of restenosis has not been fully evaluated. The aim of this study was to evaluate the relationship between the vascular features observed on optical frequency domain imaging (OFDI) before and after balloon angioplasty of femoropopliteal artery lesions, and restenosis at 6 months. This study was a prospective multicenter single arm study. OFDI was performed before and after balloon angioplasty and plaque characteristics and vascular features, along with de novo lesions, were assessed. The primary outcome was the presence or absence of restenosis 6 months after balloon angioplasty. Residual platelet reactivity was assessed according to VerifyNow platelet reactivity units (PRUs). The number of patients completing 6 months of follow-up was 47, of which 14 had developed restenosis. Maximum thickness of the dissection flap (odds ratio (OR) 2.71; 95% confidence interval [0.9-8.0]; p = 0.071) and lesion length were identified as risk factors for restenosis (OR 1.015; 95% confidence interval [0.001-0.029]; p = 0.039). The mean PRU at the time of treatment in patients with restenosis was significantly higher than in those without restenosis (286.3 ± 82.6 vs. 208.5 ± 03.6, p = 0.026). Long lesions and major dissection on OFDI after balloon angioplasty for femoropopliteal artery lesions increase restenosis at 6 months. In addition, high residual platelet reactivity at the time of EVT may also be a risk factor for restenosis.Clinical Trial Registration Number UMIN000021120.

Open-Label Multicenter Registry on the Outcomes of In-Stent Restenosis Treated by Balloon Angioplasty with Optical Frequency Domain Imaging in the Superficial Femoral Artery (ISLAND-SFA Study).

Objectives: Balloon angioplasty for in-stent restenosis (ISR) in the superficial femoral artery (SFA) has a high recurrent restenosis rate; however, its mechanism has not been fully and precisely evaluated using high-resolution intravascular imaging. Thus, we aimed to evaluate the relationship between vascular features obtained by optical frequency domain imaging (OFDI) and recurrent restenosis at 6 months. Methods: This was a prospective multicenter single-arm study. OFDI was performed before and after balloon angioplasty, and vascular features were assessed. A multi-layered ISR pattern detected by OFDI was defined as several signal-poor appearances with a high-signal band adjacent to the luminal surface. The primary outcome was defined as recurrent restenosis 6 months after balloon angioplasty. Results: Given that this study was terminated early, only 18 patients completed the 6-month follow-up; of these, 8 developed restenosis. Recurrent restenosis at 6 months tended to be related to a multi-layered ISR pattern (odds ratio (OR), 6.67; 95% confidence interval (CI), 0.81-54.96; p=0.078) and the minimum lumen area (MLA) after balloon angioplasty (OR, 0.71; 95%CI, 0.48-1.04; p=0.077). Conclusion: A multi-layered ISR pattern and MLA after balloon angioplasty detected by OFDI might be risk factors for recurrent ISR in the SFA.

Acute Pulmonary Hypertension Crisis after Adalimumab Reduction in Rheumatoid Vasculitis.

Rheumatoid vasculitis is a rare etiology for pulmonary hypertension (PH) in patients with connective tissue disease. We encountered a case of acute PH crisis in a case with rheumatoid vasculitis eight months after undergoing adalimumab reduction. Since no repetition of arthralgia occurred after the adalimumab reduction, we decided to not increase the dose of adalimumab. However, hemodynamic collapse thereafter developed and even though steroid pulse therapy was administered, the patient nevertheless died. The autopsy showed clusters of acute and chronic inflammation around the remodeled pulmonary arteries along with micro-thrombi in the vessel lumen. We should consider the possibility of critical worsening of PH as a phenotype of vasculitis related to immunosuppressive therapy reduction.

Pulmonary Endarterectomy and Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension　- Similar Effects on Health-Related Quality of Life.

Background: While hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) can be improved by invasive therapy such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA), there has been little data on the health-related quality of life (HRQOL) in such patients. Methods and Results: This single-center and observational study compared the impact of invasive therapy on HRQOL. We utilized the Medical Outcome Study 36-Item Short Health Survey (SF-36) to measure HRQOL and compared HRQOL changes after PEA and BPA. A total of 48 patients were diagnosed with CTEPH. Of these, 39 patients completed questionnaires before and after invasive therapy. The PEA group (n=15) and the BPA group (n=24) had similar improvements in clinical parameters. With regard to HRQOL score, both groups had fairly low scores in physical functioning (PF), role physical (RP), general health (GH), social functioning (SF), role emotional (RE), and physical component summary (PCS) at baseline. PF, GH, vitality (VT), mental health (MH), and PCS had significant improvements in the PEA group while PCS and all subscales except for bodily pain (BP) had significant improvements in the BPA group. Furthermore, changes between baseline and follow-up were not significantly different between the 2 groups. Conclusions: BPA for patients who are ineligible for PEA can recover HRQOL to a similar level to that achieved by PEA.

Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin.

BACKGROUND: Although a recent clinical trial demonstrated that alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduces the incidence of acute coronary events, the impact of alirocumab on plaque stabilization remains uncertain. The Efficacy of ALirocumab for Thin-cap fibroatheroma in patients with coronary Artery disease estImated by optical coherence tomogRaphy (ALTAIR) study will investigate the effect of alirocumab on thin-cap fibroatheroma (TCFA) in Japanese patients who underwent recent percutaneous coronary intervention (PCI). METHODS AND DESIGN: ALTAIR is a phase IV, open-label, randomized, parallel-group, single-center study involving blinded optical coherence tomography (OCT) image analysis in Japanese adults hospitalized for PCI and having suboptimal control of low-density lipoprotein cholesterol (LDL-C) levels (>70mg/dL) despite statin therapy. Patients will be randomized (1:1) to the alirocumab arm (alirocumab 75mg every 2 weeks added to rosuvastatin 10mg/day) or the standard-of-care arm (rosuvastatin 10mg/day, with initiation and/or dose adjustment of non-statin lipid-lowering to achieve an LDL-C target of <70mg/dL). OCT imaging will be conducted at baseline and at week 36 (post-treatment). The primary objective is to compare the alirocumab and standard-of-care arms regarding the change in TCFA fibrous-cap thickness after 9 months of treatment. CONCLUSION: The outcomes of ALTAIR (ClinicalTrials.gov identifier: NCT03552432) will provide insights into the effect of alirocumab on plaque vulnerability following PCI in patients with suboptimal LDL-C control despite stable statin therapy.

Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation.

Background We evaluated the importance of high-density lipoprotein (HDL) functionality for target-lesion revascularization in patients treated with coronary stents using a rapid cell-free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol-uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow-up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow-up was performed to assess target-lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P<0.001). The CUC showed a significant inverse correlation with incidence of target-lesion revascularization (odds ratio, 0.887; P=0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target-lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.

Extensive revascularisation by balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension beyond haemodynamic normalisation.

AIMS: Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, even after BPA many patients still suffered from exertional dyspnea. Our purpose is to clarify the clinical validity of extensive revascularization by BPA (ERBPA) beyond hemodynamic normalization. METHODS AND RESULTS: 35 CTEPH patients with normalized or borderline mean pulmonary arterial pressure (mPAP) after BPA were retrospectively analyzed. We evaluated the clinical efficacy of ERBPA strategy in 15 patients (ERBPA group) by comparing with the natural course of 20 patients who could be followed without additional BPA (conventional BPA group). ERBPA reduced the number of pulmonary arterial segments with residual stenoses from 11.7±0.4 to 5.3±0.5 segments. Symptoms, six-minute walking distance, and VE/VCO2 slope were significantly improved in the ERBPA group but not the conventional BPA group, which indicated that this improvement was due to ERBPA and not merely a natural progression after hemodynamic normalization. Complications accompanied with ERBPA were fewer than that of the initial BPA therapy. CONCLUSION: ERBPA targeting residual stenoses can safely ameliorate symptoms and exercise capacity by additional improvement of hemodynamics. The results encourage us to optimize the current BPA goal to be more aggressive.

Reversible Parkinsonism and Multiple Cerebral Infarctions after Pulmonary Endarterectomy in a Patient with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary hypertension (CTEPH) and it is associated with an increased risk of postoperative neurological complications. We experienced a case of reversible parkinsonism after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions under standard anticoagulation therapy in a patient with CTEPH associated with APS. Strict management using a combination of antiplatelet and anticoagulation therapy should be considered in patients with a high titer of triple antiphospholipid antibodies in the perioperative period. We should be aware of the high risk of postoperative neurologic manifestations in patients with APS.

Upfront triple combination therapy-induced pulmonary edema in a case of pulmonary arterial hypertension associated with Sjogren's syndrome.

Clinical efficacy of combination therapy using vasodilators for pulmonary arterial hypertension (PAH) is well established. However, information on its safety are limited. We experienced a case of primary Sjogren's syndrome associated with PAH where the patient developed pulmonary edema immediately after the introduction of upfront triple combination therapy. Although the combination therapy successfully stabilized her pre-shock state, multiple ground glass opacities (GGO) emerged. We aborted the dose escalation of epoprostenol and initiated continuous furosemide infusion and noninvasive positive pressure ventilation (NPPV), but this did not prevent an exacerbation of pulmonary edema. Chest computed tomography showing diffuse alveolar infiltrates without inter-lobular septal thickening suggests the pulmonary edema was unlikely due to cardiogenic pulmonary edema and pulmonary venous occlusive disease. Acute respiratory distress syndrome was also denied from no remarkable inflammatory sign and negative results of drug-induced lymphocyte stimulation tests (DLST). We diagnosed the etiological mechanism as pulmonary vasodilator-induced trans-capillary fluid leakage. Following steroid pulse therapy dramatically improved GGO. We realized that overmuch dose escalation of epoprostenol on the top of dual upfront combination poses the risk of pulmonary edema. Steroid pulse therapy might be effective in cases of vasodilator-induced pulmonary edema in Sjogren's syndrome associated with PAH.

The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

Potent effect of prasugrel on acute phase resolution of intra-stent athero-thrombotic burden after percutaneous intervention to acute coronary syndrome.

BACKGROUND: Recent studies suggested protruding thrombus and atheroma after stent placement could be a substrate for subsequent adverse ischemic events. Although protruded atherothrombotic burden can be assessed as intra-stent tissue (IST) by optical coherence tomography (OCT), the effects of potent antiplatelet therapy on the acute phase resolution of IST in patients with acute coronary syndrome (ACS) was unknown. METHODS: Ninety-six consecutive ACS patients with multi-vessel disease were enrolled in this prospective registry. In combination with aspirin, either clopidogrel or prasugrel was selected according to the date of enrolment. OCT examination was done immediately after percutaneous coronary intervention (post-PCI) and 10 days after index PCI (follow-up acute phase) to calculate averaged IST score as semi-quantitative measures of IST. High residual platelet reactivity (HRPR) was defined as platelet reactivity units (PRU)≥240 by VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA). RESULTS: Thirty two patients (38 stents) were enrolled in the prasugrel group and sixty four patients (72 stents) in the clopidogrel group. Averaged IST scores post-PCI were similar between the two groups (0.68±0.41 vs. 0.68±0.40, p=0.99), which decreased in all of the prasugrel group and in 87.5% of the clopidogrel group (p=0.02). Consequently, changes in averaged IST score (delta averaged IST score) were significantly greater in the prasugrel group compared to those in the clopidogrel group (-0.411±0.288 vs. -0.299±0.270, p=0.045). The frequency of HRPR was significantly lower in the prasugrel group (10.0% vs 32.4%, p=0.028). CONCLUSIONS: Prasugrel plus aspirin achieved greater acute phase reduction of IST than clopidogrel plus aspirin, which might underlie the clinical benefit of potent antiplatelet therapy in ACS. (UMIN000018751).