Post Pulmonary Endarterectomy Research Articles

Computed Tomography Pulmonary Angiography Prediction of Adverse Long-Term Outcomes in Chronic Thromboembolic Pulmonary Hypertension: Correlation with Hemodynamic Measurements Pre- and Post-Pulmonary Endarterectomy.

CT pulmonary angiography is commonly used in diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This work was conducted to determine if cardiac chamber size on CTPA may also be useful for predicting the outcome of CTEPH treatment. A retrospective analysis of paired CTPA and right heart hemodynamics in 33 consecutive CTEPH cases before and after pulmonary thromboendarterectomy (PTE) was performed. Semiautomated and manual CT biatrial and biventricular size quantifications were correlated with mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. The baseline indexed right atrioventricular volumes were twice the left atrioventricular volumes, with significant (p < 0.001) augmentation of left heart filling following PTE. Except for the left atrial volume to cardiac index, all other chamber ratios significantly correlated with hemodynamics. Left to right ventricular ratio cut point <0.82 has high sensitivity (91% and 97%) and specificity (88% and 85%) for identifying significant elevations of mPAP and PVR, respectively (AUC 0.90 and 0.95), outperforming atrial ratios (sensitivity 78% and 79%, specificity 82% and 92%, and AUC 0.86 and 0.91). Manual LV:RV basal dimension ratio correlates strongly with semiautomated volume ratio (r 0.77, 95% CI 0.64-0.85) and is an expeditious alternative with comparable prognostic utility (AUC 0.90 and 0.95). LV:RV dimension ratio of <1.03 and ≤0.99 (alternatively expressed as RV:LV ratio of >0.97 and ≥1.01) is a simple metric that can be used for CTEPH outcome prediction.

The Role of Pulmonary Compliance in the Surgical Management of Chronic Thromboembolic Pulmonary Hypertension

Pulmonary endarterectomy (PEA) offers a potentially curable treatment for chronic thromboembolic pulmonary hypertension (CTEPH). However, outcomes are often unpredictable, with residual high pulmonary vascular resistance (PVR) and persisting symptoms frequently observed despite successful resection of thromboembolic material. The severity of CTEPH is predominantly based on the magnitude of PVR and successful treatment defined by the normalisation of PVR post PEA. Pulmonary compliance (PCa), the distensibility of the arterial wall, characteristically decreases in CTEPH, even preceding increases in PVR; however, it is not routinely measured in these patients.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-analysis.

To perform a systematic review and meta-analysis assessing the safety and efficacy of balloon pulmonary angioplasty (BPA) in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Systematic literature searches were performed from inception to June 2022 to identify studies assessing BPA for CTEPH. Outcomes of interest included the following functional and hemodynamic measures: (a) six-minute walk distance (6MWD), (b) New York Heart Association (NYHA) status, (c) World Health Organization (WHO)-Functional Class status, (d) cardiac index (CI), (e) mean pulmonary artery pressure (mPAP), (f) mean right atrial pressure (mRAP), and (g) pulmonary vascular resistance (PVR). Subgroup analysis was also performed for BPA in post-pulmonary endarterectomy (PEA) patients. All reported BPA-related complications were also recorded. Forty unique studies with a total of 1763 patients were identified for meta-analysis. All functional and hemodynamic parameters improved significantly following BPA; 6MWD increased 70m (95% CI 58-82; P < 0.001), NYHA class improved by - 0.9 classes (95% CI - 1.0 to - 0.8; P < 0.001), WHO-FC class improved by - 1 classes ((95% CI - 1.2 to - 0.9; P < 0.001), CI increased 0.26 L/min/m2 (95% CI 0.17-0.35; P < 0.001), mPAP decreased - 13.2mmHg (95% CI - 14.7 to - 11.8; P < 0.001), mRAP decreased - 2.2mmHg (95% CI - 2.8 to - 1.6; P < 0.001), and PVR decreased - 311 dyne/cm/s-5 (95% CI - 350 to - 271; P < 0.001). Meta-analysis of patients who underwent BPA for persistent pulmonary hypertension post-PEA demonstrated significant improvements in 6MWD, WHO-FC, PVR and mPAP. Most common complications included lung injury (8.16%), hemoptysis (7.07%) and vessel injury (5.05%). BPA represents a safe and effective treatment option for select individuals with CTEPH with significant improvements in hemodynamic parameters, improved exercise tolerance and a relatively low risk of major complications.

Balloon Pulmonary Angioplasty in Patients With Inoperable or Recurrent/Residual Chronic Thromboembolic Pulmonary Hypertension: A Single-Centre Initial Experience

Patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) are often treated with pulmonary arterial hypertension-specific drugs. However, most of these patients remain symptomatic, despite medical treatment. Balloon pulmonary angioplasty (BPA) is an emerging therapeutic intervention for patients with inoperable CTEPH. This study aimed to report the initial experience of BPA in a tertiary referral centre for CTEPH. A total of 26 consecutive patients, who underwent 91 BPA sessions, were included in the study. All patients underwent a detailed examination, including 6-minute walking distance (6MWD), and right heart catheterisation at baseline and 3 months after the last BPA session. The mean age of the patients was 51±17 years. Fifteen (15) patients had inoperable CTEPH and 11 patients had residual or recurrent CTEPH post pulmonary endarterectomy (PEA). Functional class improved in 17 of 26 (65%) patients. The 6MWD increased from a mean 315±129 to 411±140 m (p<0.001), and NT pro-BNP reduced from a median 456 to 189 pg/mL (p=0.001). The number of patients who required supplemental oxygen decreased from 11 (42.3%) to five (19%) (p=0.031) after BPA treatment. The mean pulmonary artery pressure decreased from a mean 47.5±13.4 to 38±10.9 mmHg (p<0.001), the pulmonary vascular resistance decreased from a mean 9.3±4.7 to 5.8±2.8 Wood units (p<0.001), and the cardiac index increased from a mean 2.4±0.7 to 2.9±0.6 L/min/m2 (p=0.008). Balloon pulmonary angioplasty improved haemodynamics, 6MWD, and functional class, and reduced the requirement for supplemental oxygen, with an acceptable risk-benefit ratio in patients with inoperable CTEPH and with residual/recurrent CTEPH.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: state-of-the-art 2020.

Pulmonary endarterectomy is the treatment of choice for patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) as it is potentially curative. In expert centers that conduct > 50 pulmonary endarterectomy procedures per year, peri- and post-surgical mortality rates are very low and long-term outcomes are excellent, with three-year post-operative survival of > 80%. Therapeutic decisions in CTEPH are based largely on the location of the arterial obstruction, with pulmonary endarterectomy for obstructions in main, lobar, and segmental vessels, and balloon pulmonary angioplasty and medical therapy for small-vessel disease. Medical therapy is also an option for patients with persistent/recurrent pulmonary hypertension after pulmonary endarterectomy or balloon pulmonary angioplasty. With increasing surgical experience and improvements in instruments and procedures, an increasing number of patients are now considered operable who would previously have been inoperable, including some patients with subsegmental disease. At our University (University of California San Diego), around 200 pulmonary endarterectomy procedures are performed every year and several advances have been developed, including resection of more distal disease, availability of pulmonary endarterectomy to patients previously considered to be at too high risk for surgery, improved management of post-pulmonary endarterectomy complications, and minimally invasive pulmonary endarterectomy. Pulmonary endarterectomy can be combined with other treatment modalities, including balloon pulmonary angioplasty, medical therapy for persistent/recurrent pulmonary hypertension after pulmonary endarterectomy, and medical therapy or balloon pulmonary angioplasty as bridging therapy before surgery. Data on these combinations are, however, limited. Combination treatment should therefore be considered on an individual patient basis. In the future, however, multimodal therapy with pulmonary endarterectomy, balloon pulmonary angioplasty, and/or medical therapy is likely to be an important treatment option for many patients.

Beneficial effects of balloon pulmonary angioplasty on clinical outcomes in patients with residual pulmonary hypertension after pulmonary endarterectomy

Abstract Background Although pulmonary endarterectomy (PEA) is an established surgical treatment for chronic thromboembolic pulmonary hypertension (CTEPH), a part of patients after PEA show residual pulmonary hypertension, leading to limited exercise capacity. Recently, several studies have indicated that balloon pulmonary angioplasty (BPA) improves hemodynamics, exercise capacity and prognosis in inoperable CTEPH patients. However, the effects of BPA in patients with residual pulmonary hypertension after PEA remain to be elucidated. Aim In the present study, we investigated comprehensive efficacy of BPA on hemodynamics, exercise capacity and right ventricular function in those with residual pulmonary hypertension after PEA. Methods From October 2010 to February 2019, 227 patients with CTEPH underwent PEA in our institution. Right heart catheterization after PEA (median follow up period from PEA to right heart catheterization 39 [10.5, 90] months) showed that 55 patients showed residual PH (mean pulmonary artery pressure (mPAP)≥25mmHg), and 38 of them referred to BPA (mean age 57 years old, male 8 (21%)) due to residual symptoms. In 29 out of 38 patients (76%) who completed BPA and underwent follow-up right heart catheterization, we examined hemodynamics, exercise capacity and right ventricular function before and after BPA. Follow-up examination was performed 3 months after last BPA session. Results In this study population (N=29), PEA significantly improved mPAP (47±7 to 38±10 mmHg), pulmonary vascular resistance (PVR, 14.6±4.6 to 9.2±4.6 WU) and right ventricular ejection fraction measured by magnetic resonance imaging (26.6±11.3 to 38.4±6.8%) (Figure). Median period from PEA to first BPA procedure was 42 [13.5, 94] months. Total session number during study period was 160 sessions, and mean session number of BPA was 5.5±1.5 per patient. Follow-up study revealed that BPA additionally improved mPAP (38±10 to 27±8 mmHg) and PVR (9.2±4.6 to 5.1±2.2 WU) (Figure). Similarly, 6-minute walk distance (393±125 to 452±125 m) and peak VO2 (16.4±3.8 to 18.1±4.6 ml/min/kg, p&amp;lt;0.05) were increased, and WHO functional class also significantly improved by BPA (I/II/III/IV, 0/21/8/ 0 to 1/27/1/0, p&amp;lt;0.01). In addition, right ventricular ejection fraction (38.4±6.8 to 44.2±7.1%) was increased after BPA (Figure). There were no procedure-related deaths and major lung injuries requiring oral intubation during study period. 3-year survival in patients after BPA was 100% (median follow-up period after last BPA session, 32 [18, 46] months). Conclusion In CTEPH patients with residual pulmonary hypertension after PEA, additional BPA significantly improved hemodynamics, right ventricular function, exercise capacity and residual symptoms without severe complications, leading to good prognosis. These results suggest that combination therapy of PEA and BPA could be an effective therapeutic option for post PEA patients with residual symptoms and exercise limitation. Figure 1 Funding Acknowledgement Type of funding source: None

Extracorporeal Life Support in Hemorrhagic Conditions: A Systematic Review.

Extracorporeal life support (ECLS) is indicated in refractory acute respiratory or cardiac failure. According to the need for anticoagulation, bleeding conditions (e.g., in trauma, pulmonary bleeding) have been considered a contraindication for the use of ECLS. However, there is increasing evidence for improved outcomes after ECLS support in hemorrhagic patients based on the benefits of hemodynamic support outweighing the increased risk of bleeding. We conducted a systematic literature search according to the PRISMA guidelines and reviewed publications describing ECLS support in hemorrhagic conditions. Seventy-four case reports, four case series, seven retrospective database observational studies, and one preliminary result of an ongoing study were reviewed. In total, 181 patients were identified in total of 86 manuscripts. The reports included patients suffering from bleeding caused by pulmonary hemorrhage (n = 53), trauma (n = 96), postpulmonary endarterectomy (n = 13), tracheal bleeding (n = 1), postpartum or cesarean delivery (n = 11), and intracranial hemorrhage (n = 7). Lower targeted titration of heparin infusion, heparin-free ECLS until coagulation is normalized, clamping of the endotracheal tube, and other ad hoc possibilities represent potential beneficial maneuvers in such conditions. Once the patient is cannulated and circulation restored, bleeding control surgery is performed for stabilization if indicated. The use of ECLS for temporary circulatory or respiratory support in critical patients with refractory hemorrhagic shock appears feasible considering tailored ECMO management strategies. Further investigation is needed to better elucidate the patient selection and ECLS management approaches.

Outcomes of Patients with Chronic Thromboembolic Pulmonary Hypertension Risk Stratified by a Dedicated Heart Team to Receive Pulmonary Endarectomy or Balloon Pulmonary Angiogiplasty

Chronic thromboembolic pulmonary hypertension (CTEPH) is progressive condition characterised by fibro-thrombotic obstruction of pulmonary arteries, and is associated with significant mortality. Given techniques are evolving, there is still considerable variation in the literature regarding surgical and interventional outcomes. This study aims to determine outcomes for CTEPH patients undergoing pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in specialist pulmonary hypertension unit with treatment modality determined by a multi-disciplinary heart team. This is a retrospective cohort study of all patients undergoing PEA or BPA between 2002 and June 2018. A team of experienced cardiologists, surgeons and interventional radiologists made decisions regarding treatment modality. Both haemodynamic, clinical and procedural outcomes were measured, and comparison was made between treatment groups. Only patients who had available pre- and post intervention right heart catheter data were included in the haemodynamic analysis. A total of 92 patients were included between the PEA group (n=65, age 58 ± 16, m=32, f= 33) and BPA group (n=27, age 65 ± 17, m=15, F=12). For haemodynamic outcomes, a total 52 patients (42 PEA, 10 BPA) were included. There were statistically significant improvements in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), mean right atrial pressure and cardiac index. Though the reductions in mPAP (PEA 21 mmHg vs. BPA12.5 mmHg) and PVR (PEA 527 ± 350 dyn.s.cm-5 vs. BPA 304 dyn.s.cm-5) were more marked in the PEA group, there was no statistically significant difference between the groups. There were two deaths (3%) post PEA and one death (3.7%) encountered post-BPA. We conclude, that with careful patient selection and experienced proceduralists, there is significant improvement in haemodynamic outcomes with both surgery and intervention, and an acceptable complication profile.

Chronic Thromboembolic Pulmonary Hypertension Perioperative Monitoring Using Phase-Resolved Functional Lung (PREFUL)-MRI.

The translation of phase-resolved functional lung (PREFUL)-MRI to routine practice in monitoring chronic thromboembolic pulmonary hypertension (CTEPH) still requires clinical corresponding imaging biomarkers of pulmonary vascular disease. To evaluate successful pulmonary endarterectomy (PEA) via PREFUL-MRI with pulmonary pulse wave transit time (pPTT). Retrospective. Thirty CTEPH patients and 12 healthy controls were included. For PREFUL-MRI a 2D spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence were performed on 1.5T. Eight coronal slices of PREFUL-MRI were obtained on consecutive 13 days before and 14 days after PEA. PREFUL quantitative lung perfusion (PREFULQ ) phases over the whole cardiac cycle were calculated to quantify pPTT, the time the pulmonary pulse wave travels from the central pulmonary arteries to the pulmonary capillaries. Also, perfusion defect percentage based on pPTT (QDPpPTT ), PREFULQ (QDPPREFUL ), and V/Q match were calculated. For DCE-MRI, pulmonary blood flow (PBF) and QDPPBF were computed as reference. For clinical correlation, mean pulmonary arterial pressure (mPAP) and 6-minute walking distance were evaluated preoperatively and after PEA. The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Dice coefficient, and Spearman's correlation coefficient (ρ) were applied. Median pPTT was significantly lower post PEA (139 msec) compared to pre PEA (193 msec), P = 0.0002. Median pPTT correlated significantly with the mPAP post PEA (r = 0.52, P < 0.008). Median pPTT was distributed more homogeneously after PEA: IQR pPTT decreased from 336 to 281 msec (P < 0.004). Median PREFULQ (P < 0.0002), QDPpPTT (P < 0.0478), QDPPREFUL (P < 0.0001) and V/Q match (P < 0.0001) improved significantly after PEA. Percentage change of PREFULQ correlated significantly with percentage change of 6-minute walking distance (ρ = 0.61; P = 0.0031) 5 months post PEA. Perioperative perfusion changes in CTEPH can be detected and quantified by PREFUL-MRI. Normalization of pPTT reflects surgical success and improvement of PREFULQ predicts 6-minute walking distance changes. 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:610-619.

144 Outcomes of Patients With Chronic Thromboembolic Pulmonary Hypertension Risk Stratified by a Dedicated Heart Team to Receive Pulmonary Endarectomy or Balloon Pulmonary Angiogiplasty

Chronic thromboembolic pulmonary hypertension (CTEPH) is progressive condition characterised by fibro-thrombotic obstruction of pulmonary arteries, and is associated with significant mortality. To determine outcomes for CTEPH patients undergoing pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in specialist pulmonary hypertension unit with treatment modality determined by a multidisciplinary heart team. This is a retrospective cohort study of all patients undergoing PEA or BPA between 2002 and June 2018. A team of experienced cardiologists, surgeons and interventional radiologists made decisions regarding treatment modality. Both haemodynamic, clinical and procedural outcomes were measured, and comparison was made between treatment groups. Only patients who had available pre- and post intervention right heart catheter data were included in the haemodynamic analysis. A total of 92 patients were included between the PEA group (n=65, age 58±16, m=32, f=33) and BPA group (n=27, age 65±17, m=15, F=12). For haemodynamic outcomes, a total 52 patients (42 PEA, 10 BPA) were included. There were statistically significant improvements in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), mean right atrial pressure and cardiac index. Though the reductions in mPAP (PEA 21 mmHg vs BPA12.5 mmHg) and PVR (PEA 527±350 dyn.s.cm-5 vs BPA 304 dyn.s.cm-5) were more marked in the PEA group, there was no statistically significant difference between the groups. There were two deaths (3%) post PEA and one death (3.7%) encountered post-BPA. This is the first centre in Australia to offer PEA and BPA, and the results capture the program. We conclude, that with careful patient selection and experienced proceduralists, there is significant improvement in haemodynamic outcomes with both surgery and intervention, and an acceptable complication profile.

Perfusion strategy and mid-term results of 58 consecutive pulmonary endarterectomy.

The aim of this retrospective study was to review and report short-term and mid-term outcomes of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at our institute in the recent 2 years and to describe perfusion strategy. A total of 58 consecutive patients with chronic thromboembolic pulmonary hypertension underwent pulmonary endarterectomy under deep hypothermia circulatory arrest with an established perfusion practice between November 2015 and December 2017. Peri-operative data and patients' outcome were retrospectively analyzed. Mean pulmonary artery pressure was decreased (49 (40-56) mmHg vs 27 (20-31) mmHg, p < 0.001), and pulmonary vascular resistance (724 (538-1108) vs 206 (141-284) dyn second cm-5, p < 0.001) improved significantly after surgery. In-hospital mortality was 1.7% and postoperative complication rate was 27.6%. Antipsychotic medication of olanzapine was prescribed for 36 patients (62.1%), which was independently related to total deep hypothermic circulatory arrest time, postoperative blood potassium concentration, and hematocrit. The majority of patients recovered uneventfully with good mid-term cardiac function (New York Heart Association I-II: 98.1%) and neurological outcome (Glasgow Outcome Scale-Extended Upper Good Recovery: 74.1% and Lower Good Recovery: 20.3%). Mid-term neurological outcome was associated with post-pulmonary endarterectomy antipsychotic medication. Short-term and mid-term outcome after pulmonary endarterectomy was comparable to high-volume centers. Incidence of post-pulmonary endarterectomy delirium was relatively high and associated with mid-term neurological outcome. Total deep hypothermic circulatory arrest time, postoperative blood potassium concentration, and hematocrit were independent risk factors of postoperative olanzapine medication. More efforts and further research are required to optimize the neuroprotection of perfusion practice.

High preoperative plasma endothelin-1 levels are associated with increased acute kidney injury risk after pulmonary endarterectomy.

The only curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). PEA requires cardiopulmonary bypass (CPB) which is associated with a high acute kidney injury (AKI) risk. Circulating endothelin-1 (ET-1) levels are elevated in CTEPH, and ET-1 plays a pivotal role in AKI. Because AKI is burdened by high morbidity and mortality, we aimed to evaluate the association between preoperative ET-1 and the risk to develop AKI in CTEPH individuals who undergo PEA. We also evaluated the association of AKI and ET-1 with kidney function and mortality at 1year after PEA. In 385 consecutive patients diagnosed with CTEPH who underwent PEA at the Foundation IRCC Policlinico San Matteo (Pavia, Italy) from January 2009 to April 2015, we assessed preoperative circulating ET-1 by ELISA and identified presence of AKI based on 2012 KDIGO criteria. AKI occurred in 26.5% of the 347 patients included in the analysis, and was independently associated with preoperative ET-1 (p = 0.008), body mass index (BMI) (p = 0.022), male gender (p = 0.005) and duration of CPB (p = 0.002). At 1-year post PEA, estimated glomerular filtration rate (eGFR) significantly improved in patients who did not develop AKI [ΔeGFR 5.6ml/min/1.73m2 (95% CI 3.6-7.6), p < 0.001] but not in those with perioperative AKI. AKI (p < 0.001), age (p < 0.001), preoperative eGFR (p < 0.001) and systemic hypertension diagnosis (p = 0.015) were independently associated with 1-year ΔeGFR. Neither perioperative AKI nor preoperative ET-1 was associated with 1-year survival. Perioperative AKI is associated with higher preoperative circulating ET-1 and it negatively influences long-term kidney function in patients with CTEPH who undergo PEA.

Abstract 20987: Pulmonary Blood Volume Evaluated by Dual-Energy CT is a New Maker for the Management of Chronic Thromboembolic Pulmonary Hypertension

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary obstructive vascular disease. But there were few methods to quantify lung blood perfusion. In dual-energy CT (DECT), two image datasets are acquired in the same anatomic location using two different tube potentials. DECT can produce a more sensitive iodine distribution map image than conventional CT, which enable us to quantify blood perfusion in lung fields. There were few reports showing the clinical significance of DECT in CTEPH. Methods: We enrolled 59 consecutive CTEPH patients who underwent DECT from Jan. 2015 to Feb. 2017. We evaluated the relations between DECT parameter as lung pulmonary blood volume (PBV) and clinical parameters from 6-min walk distance (6MWD), respiratory function test, cardiopulmonary exercise test (CPX), and right heart catheterization (RHC). Results: In 59 patients (female 41, mean age 60.0±13.6 years old), two patients were WHO functional class (WHO-Fc) IV, 28 were WHO-Fc III, 23 were WHO-Fc II, six were WHO-Fc I. 28 patients were evaluated at pre-treatment, nine at post pulmonary endarterectomy (PEA), 18 at post balloon pulmonary angioplasty (BPA), and four at post hybrid therapy (PEA and BPA). The average of PBV were 25.4±7.4 Hounsfield Unit. Mean pulmonary arterial pressure (mPAP) were 29.5±12.9 mmHg, pulmonary vascular resistance (PVR) were 553±404 dyne*sec/cm5, cardiac index were 2.3±0.7 l/min/m2. The value of PBV was well reflected with WHO-Fc classification. (I/II/III/IV=31.8±6.4/27.1±7.4/22.8±6.2/23.5±13.4; ANOVA p=0.019), and was significantly correlated with mPAP (r = -0.57, p &lt; 0.01), PVR (r = -0.60, p &lt; 0.01), VE/VCO2 slope (r =- 0.47, p &lt; 0.01), BNP level (r = -0.60, p &lt; 0.01). Conclusion: PBV was positively correlated with symptom, hemodynamics, exercise capacity, and BNP level in the patients of CTEPH, suggesting that PBV by DCET can work as a new management index from a perspective of pulmonary blood perfusion.

The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk of clinically relevant bleeding, recurrent VTE, and clinical worsening in patients with CTEPH who were administered warfarin.The clinical records of 72 patients with CTEPH who regularly visited our institution and were administered warfarin were retrospectively reviewed between 1 January 2011 and 31 December 2015. We investigated the incidence of clinically relevant bleeding events, recurrent VTE, and hospitalization for the deterioration of pulmonary hypertension or right heart failure (RHF) during the observation period.The mean observation period for the 72 patients was 3.60 ± 1.60 person-years. Clinically relevant bleeding, RHF, and recurrent VTE occurred in 21 (29.2%), eight (11.1%), and three (4.2%) of 72 patients, respectively, and the incidence rates for these events were 8.1%/person-year, 3.1%/person-year, and 1.2%/person-year, respectively. The incidence rates for the major and non-major bleeding events were 5.0%/person-year and 3.9%/person-year, respectively. The incidence of clinically relevant bleeding events was 20.8%/person-year during medical treatment with a soluble guanylate cyclase stimulator. One of 35 patients (2.9%) during the post-pulmonary endarterectomy period experienced hemoptysis during observation period (> 6 months after pulmonary endarterectomy). No bleeding events occurred during the post-balloon pulmonary angioplasty period.In conclusion, warfarin effectively prevents VTE recurrence in CTEPH patients, but its effects may be associated with a considerable bleeding risk.

The Clinical Impact of Referral Time in Patients With Pulmonary Hypertension on Disease Progression: A Register Analysis of a Tertiary Referral Center

Although surgery is the treatment of choice for CTEPH, it is not appropriate for patients with surgically inaccessible distal disease. These patients are traditionally managed supportively, but may benefit from newer, more specific vasoactive therapies. This study examines the acute haemodynamic responses to inhaled nitric oxide (iNO) and intravenous sildenafil in this patient population.Nine patients with de novo distal CTEPH and nine with persistent pulmonary hypertension post-pulmonary endarterectomy (PEA) were enrolled. At right heart catheterisation, following baseline haemodynamic measurements, iNO was administered at 20 ppm for 10 min. Following repeat measurements, iNO was discontinued with a subsequent washout period of 10 min. Sildenafil was then administered intravenously at two doses, to achieve plasma levels equivalent to 25 mg and 50 mg orally, with further measurements obtained at the end of each infusion.Significant reductions in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were demonstrated following both iNO (− 4.3 mm Hg or − 10.3% p = 0.001 and − 101 dyn/s/cm5 or − 15.6% p < 0.001) and sildenafil (− 7.4 mm Hg or − 16.9% p < 0.001 and − 188.8 dyn/s/cm5 or − 25.1% p < 0.001). Individual mPAP and cardiac output (CO) responses to iNO and sildenafil correlated well, but haemodynamic changes following sildenafil were consistently more marked. There was, however, no difference in effect between the two doses of sildenafil. Although sildenafil caused significant reductions in systemic vascular resistance, the net haemodynamic effect of sildenafil remained pulmonary selective. Subgroup analysis suggested that post-PEA patients were more responsive to both iNO and sildenafil than de novo patients.Although all but one patient failed to fulfil the formal haemodynamic response criteria typically used in idiopathic pulmonary arterial hypertension (IPAH), subjects displayed significant acute responses to both iNO and sildenafil suggesting that increased vascular tone forms an important component of distal CTEPH. It is possible that these acute haemodynamic responses may translate to improved clinical outcomes, and thus further long term trials of sildenafil in distal CTEPH are warranted.

Development and Characterization of an Inducible Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not only limits patients quality of life but also causes significant morbidity and mortality. The treatment of choice is pulmonary endarterectomy. However numerous patients do not qualify for pulmonary endarterectomy or present with residual vasculopathy post pulmonary endarterectomy and require specific vasodilator treatment. Currently, there is no available specific small animal model of CTEPH that could serve as tool to identify targetable molecular pathways and to test new treatment options. Thus, we generated and standardized a rat model that not only resembles functional and histological features of CTEPH but also emulates thrombi fibrosis. The pulmonary embolism protocol consisted of 3 sequential tail vein injections of fibrinogen/collagen-covered polystyrene microspheres combined with thrombin and administered to 10-week-old male Wistar rats. After the third embolism, rats developed characteristic features of CTEPH including elevated right ventricular systolic pressure, right ventricular cardiomyocyte hypertrophy, pulmonary artery remodeling, increased serum brain natriuretic peptide levels, thrombi fibrosis, and formation of pulmonary cellular-fibrotic lesions. The current animal model seems suitable for detailed study of CTEPH pathophysiology and permits preclinical testing of new pharmacological therapies against CTEPH.

(416) - Pre-operative Use of Pulmonary Arterial Hypertension-Targeted Medication and the Effects on Post-Pulmonary Endarterectomy Morbidity and Mortality

The definitive treatment for chronic thromboembolic pulmonary hypertension remains a pulmonary endarterectomy (PEA) at an experienced surgical center. Despite this recommendation, many patients with surgically accessible disease are pre-treated with pulmonary arterial hypertension-targeted medications. The effects of such a strategy on post-operative outcomes are not well defined.

P16 A Systematic Characterisation Of Inflammation In Chronic Thromboembolic Pulmonary Hypertension

Introduction The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is poorly understood. Idiopathic pulmonary arterial hypertension (IPAH) is associated with systemic and localised inflammation. Distal vasculopathy is seen in IPAH and CTEPH (2 compartment model). Inflammation has also been implicated in CTEPH pathogenesis. We undertook a systematic assessment of inflammatory markers and immune cells to determine the role of inflammation in CTEPH. Methods We examined the distal tails of 26 pulmonary endarterectomy (PEA) specimens and explanted lungs (5 CTEPH, 11 IPAH). Formalin fixed samples were immunostained with anti-human CD45 (inflammatory cell), CD79a (B cell), CD68 (macrophage) or CD3 (T cell) antibodies. Cell counts were normalised to the area surrounding vessels bounded by airspace structures for perivascular cell counts; to vessel area for media cell counts and per high powered field for lung parenchymal cell counts. Serum was collected from 61 patients pre and 6 months post PEA. Cytokines were measured using a multiplex array (pg/ml; mean±SD). Results Table 1. CD3 + cells were less abundant in the media of small vessels (mean 0.03 ± 0.01 mm 2 ) in CTEPH vs. IPAH (p = 0.02). Perivascular and parenchymal cell counts showed non-significant reductions of CD3 + cells in CTPEH (p = 0.19 and 0.08 respectively). More CD68 + cells were seen in the parenchyma in CTEPH (p = 0.03). Few CD20 + cells were seen in parenchyma with no difference. Neovascularisation correlated to CD45 + cells in PEA specimens when normalised to specimen area (r = 0.4, p = 0.01). Conclusions In CTEPH, most serum cytokines were not elevated sufficiently to suggest systemic inflammation is important in pathogenesis. The change in IL10 and TNFα are possibly due to improvement in cardiac function post PEA as described previously. The relative lack of CD3 + T cells in the media of small arteries in CTEPH suggests that localised inflammation is also less important. The significance of CD68 + cells in CTEPH lung parenchyma needs further assessment. The correlation of CD45 + cells and neovascularisation in PEA specimens may suggest an association between inflammation and neovascularisation. Inflammatory signals maybe related to thrombus remodelling and cardiac dysfunction rather than to CTEPH pathogenesis. Isolating these processes is required to expand on this descriptive study.

PHPN: Post-Pulmonary Endarterectomy: What to Expect During the First Year and How to Handle the Unexpected

PHPN: Post-Pulmonary Endarterectomy: What to Expect During the First Year and How to Handle the Unexpected

Isolated Permanent Right Ventricular Assistance Using the HVAD Continuous-Flow Pump

Acute isolated right ventricular (RV) failure from myocardial infarction is a rare scenario. To date, there are no assist devices developed or approved for permanent isolated right heart support. We report on the successful implantation of a HeartWare HVAD as an isolated RV assist in a patient who suffered extended RV myocardial infarction after iatrogenic dissection of the right coronary artery. No manipulations of the system were required to adapt the assist device to the pulmonary circulation.