Severe Chronic Thromboembolic Pulmonary Hypertension Research Articles

Upfront triple therapy with parenteral prostanoid as a bridge to balloon pulmonary angioplasty in severe chronic thromboembolic pulmonary hypertension.

In patients with very severe CTEPH eligible for BPA, it is possible to achieve major haemodynamic improvement with upfront triple PH therapy including epoprostenol and then to perform angioplasties https://bit.ly/3vZZvib.

Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.

Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included. Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents. In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

Patients with CTEPH and mild hemodynamic severity of disease improve to a similar level of exercise capacity after pulmonary endarterectomy compared to patients with severe hemodynamic disease.

The correlation between hemodynamics and degree of pulmonary vascular obstruction (PVO) is known to be poor in chronic thromboembolic pulmonary hypertension(CTEPH), which makes the selection of patients eligible for pulmonary endarterectomy (PEA) challenging. It can be postulated that patients with similar PVO but different hemodynamic severity have different postoperative hemodynamics and exercise capacity. Therefore, we aimed to assess the effects of PEA on hemodynamics and exercise physiology in mild and severe CTEPH patients. We retrospectively studied 18 CTEPH patients with a mild hemodynamic profile (mean pulmonary arterial pressure[mPAP] between 25 and 30 mmHg at rest) and CTEPH patients with a more severe hemodynamic profile (mPAP > 30 mmHg), matched by age, gender, and PVO. Cardiopulmonary exercise testing parameters were evaluated at baseline and 18 months following PEA. At baseline, exercise capacity, defined as oxygen uptake, was less severely impaired in the mild CTEPH group compared to the severe CTEPH group. After PEA, in the mild CTEPH group, ventilatory efficiency and oxygen pulse improved significantly (p < 0.05), however, the change in ventilatory efficiency and oxygen pulse was smaller compared to the severe CTEPH group. Only in the severe CTEPH group exercise capacity improved significantly (p < 0.001). Hence, in the present study, postoperative hemodynamic outcome and the CPET-determined recovery of exercise capacity in mild CTEPH patients did not differ from a matched group of severe CTEPH patients.

The risk profile change in patients with severe chronic thromboembolic pulmonary hypertension treated with subcutaneous treprostinil.

Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long-term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double-blind clinical trial comparing high-dose and low-dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high-dose arm vs. 8.6 in low-dose arm), but mean RRS change from baseline to Week 24 was greater in the high-dose treprostinil group than in the low-dose treprostinil group (-0.88 vs. -0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of -0.70 (95% confidence interval: -1.36 to -0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N-terminal pro-brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

Analysis of Electrocardiographic Criteria of Right Ventricular Hypertrophy in Patients with Chronic Thromboembolic Pulmonary Hypertension before and after Balloon Pulmonary Angioplasty.

Chronic thromboembolic pulmonary hypertension (CTEPH) may lead to typical electrocardiographic changes that can be reversed by balloon pulmonary angioplasty (BPA). The aim of this study was to investigate the significance of rarely used electrocardiogram (ECG) parameters, possible electrocardiographic differences between residual and significantly improved CTEPH and the role of electrocardiographic parameters in low mPAP (mean pulmonary arterial pressure) ranges since the mPAP threshold for the definition of pulmonary hypertension has recently been adjusted (≥25 mmHg to >20 mmHg). Between March 2014 and October 2020, 140 patients with CTEPH and 10 with CTEPD (chronic thromboembolic pulmonary disease) without pulmonary hypertension (PH) were retrospectively enrolled (12-lead ECG and right heart catheterization before and 6 months after BPA). The ECG parameters of right heart strain validated by studies and clinical experience were evaluated. Special attention was paid to six specific ECG parameters. After BPA, the cohort was divided into subgroups to investigate possible electrocardiographic differences with regard to the haemodynamic result. The present study confirmed that the typical electrocardiographic signs of CTEPH can be found on an ECG, can regress after BPA and partially correlate well with haemodynamic parameters. "R V1, V2 + S I, aVL - S V1" was a parameter of particular note. BPA reduced its frequency (47% vs. 29%) statistically significantly after Bonferroni correction (p < 0.001). Moreover, it showed a good correlation with mPAP and PVR (r-values: 0.372-0.519, p-values: < 0.001). Exceeding its cut-off value before therapy was associated with more severe CTEPH before therapy (higher mPAP, PVR, NT-pro-BNP and troponin and lower TAPSE) and an increased risk of death. Exceeding its cut-off value before and after therapy was associated with more severe CTEPH after therapy (higher RAP, mPAP, PVR, NT-pro-BNP and NYHA class) and an increased risk of death. Men tend to be affected more frequently. After subgrouping, it was observed that a higher median mPAP was associated with a higher right atrial pressure (RAP), a higher pulmonary vascular resistance (PVR) and a lower cardiac output (CO) before and after BPA. In addition, under these conditions, more and more severe electrocardiographic pathologies were detected before and after BPA. Some patients with low mPAP also continued to show mild ECG changes after BPA. In some cases, very few to no pathological ECG changes were detected, and the ECG could present as mostly normal in some patients (5% before BPA and 13% after BPA). "R V1, V2 + S I, aVL - S V1" seems to be able to support the diagnosis of CTEPH, indicate therapeutic improvement and estimate haemodynamics. It also seems capable of predicting a (persistent) severe disease with probably increased need for therapy and increased mortality. Mild PH has been observed to have either no or few mild ECG changes. This might complicate the (early) detection of PH.

Pulmonary endarterectomy in severe chronic thromboembolic pulmonary hypertension: the Toronto experience.

Pulmonary endarterectomy (PEA) in severe chronic thromboembolic pulmonary hypertension (CTEPH) is associated with higher risks. However, recent evidence suggests that these risks may be mitigated with the use of extracorporeal membrane oxygenation (ECMO). We performed a retrospective analysis of 401 consecutive patients undergoing PEA at the Toronto General Hospital between August 2005 and March 2020. Patients with severe CTEPH defined by pulmonary vascular resistance (PVR) >1,000 dynes.s.cm-5 at the time of diagnosis were compared to those with PVR <1,000 dynes.s.cm-5. The New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and 6-minute walk distance were worse in patients with PVR >1,000 dynes.s.cm-5. A greater proportion of patients with PVR >1,000 dynes.s.cm-5 was treated with targeted pulmonary hypertension (PH) medical therapy (38% vs. 18%, P<0.001) and initiated on inotropic support (7% vs. 0.3%, P<0.001) before PEA. Since 2014, the ECMO utilization rate increased in patients with PVR >1,000 dynes.s.cm-5 compared to those with PVR <1,000 dynes.s.cm-5 (18% vs. 3.1%, P<0.001). The hospital mortality in patients with PVR >1,000 dynes.s.cm-5 decreased from 10.3% in 2005-2013 to 1.6% in 2014-2020 (P=0.05), while the hospital mortality in patients with PVR <1,000 dynes.s.cm-5 remained stable (1.2% in 2005-2013 vs. 2.7% in 2014-2020, P=0.4). The overall survival reached 84% at 10 years in patients with PVR >1,000 dynes.s.cm-5 compared to 78% in patients with PVR <1,000 dynes.s.cm-5 (P=0.7). The early and long-term results of PEA in patients with severe CTEPH are excellent despite greater postoperative risks. ECMO as a bridge to recovery after PEA can be useful in patients with severe CTEPH.

Modulation of soluble guanylate cyclase ameliorates pulmonary hypertension in a rat model of chronic thromboembolic pulmonary hypertension by stimulating angiogenesis.

Acute pulmonary embolism (PE) does not always resolve after treatment and can progress to chronic thromboembolic disease (CTED) or the more severe chronic thromboembolic pulmonary hypertension (CTEPH). The mechanisms surrounding the likelihood of PE resolution or progress to CTED/CTEPH remain largely unknown. We have developed a rat model of CTEPH that closely resembles the human disease in terms of hemodynamics and cardiac manifestations. Embolization of rats with polystyrene microspheres followed by suppression of angiogenesis with the inhibitor of vascular endothelial growth factor receptor 2 (VEGF‐R2) SU5416 results in transient, acute pulmonary hypertension that progresses into chronic PE with PH with sustained right ventricular systolic pressures exceeding 70 mmHg (chronic pulmonary embolism [CPE] model). This model is similar to the widely utilized hypoxia/SU5416 model with the exception that the “first hit” is PE. Rats with CPE have impaired right heart function characterized by reduced VO2Max, reduced cardiac output, and increased Fulton index. None of these metrics are adversely affected by PE alone. Contrast‐mediated CT imaging of lungs from rats with PE minus SU5416 show large increases in pulmonary vascular volume, presumably due to an angiogenic response to acute PE/PH. Co‐treatment with SU5416 suppresses angiogenesis and produces the CTEPH‐like phenotype. We report here that treatment of CPE rats with agonists for soluble guanylate cyclase, a source of cGMP which is in turn a signal for angiogenesis, markedly increases angiogenesis in lungs, and ameliorates the cardiac deficiencies in the CPE model. These results have implications for future development of therapies for human CTEPH.

Cardiopulmonary exercise testing and pulmonary function testing for predicting the severity of CTEPH

BackgroundCardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aims to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively by these two methods. Moreover, the research assesses the predictive value of CPET and PFT parameters for severe CTEPH.MethodsWe used data from 86 patients with CTEPH (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET data of CTEPH patients of different severity classified according to pulmonary artery pressure (PAP) (mm Hg) were collected and compared. Logistic regression analysis was performed to appraise the predictive value of each PFT and CPET parameter for severe CTEPH. The performance of CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves.ResultsData showed that minute ventilation at anaerobic threshold (VE @ AT) (L/min) and oxygen uptake at peak (VO2 @ peak) (mL/kg/min) were independent predictors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) in identifying severe CTEPH was found to be moderate with the area under ROC curve (AUC) of 0.769 and 0.740, respectively. Furthermore, the combination of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) had a moderate utility value in identifying severe CTEPH with the AUC of 0.843.ConclusionOur research suggests that CPET and PFT can noninvasively and effectively evaluate, monitor and predict the severity of CTEPH.

TCTAP C-110 Efficacy of Serial Balloon Pulmonary Angioplasty in Treating an Octogenarian with Severe Chronic Thromboembolic Pulmonary Hypertension and Right Heart Failure

TCTAP C-110 Efficacy of Serial Balloon Pulmonary Angioplasty in Treating an Octogenarian with Severe Chronic Thromboembolic Pulmonary Hypertension and Right Heart Failure

Predictors for Chronic Thromboembolic Pulmonary Hypertension

Introduction - The most dangerous complication of acute venous thrombosis is pulmonary embolism (PE), which results directly in mortality in most cases. In non-fatal cases of massive pulmonary embolism, when thrombolytic therapy or embolectomy is not possible or ineffective, there is severe chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of our study was to develop clinical, laboratory and instrumental criteria to characterize the development of varying CTEPH intensity after the earlier is PE. Methods - The study is based on a retrospective material comprising 26 patients with the pulmonary embolism arteries and survived it. At different times (1-5 years) after the event and discharge from the hospital, the patients were summoned and examined. All patients were performed to an ultrasonography of the lower limbs, echocardiography, and some patients had pulmonary perfusion scintigraphy and CT angiography. In case of high pulmonary hypertension, which was detected with echocardiography, the right heart catheterization was used for the immediate detection of pulmonary pressure. In the course of our study, we compared the patients' findings received in the initial hospital admissions with the findings of clinical and instrumental methods we had received in the long term after the pulmonary embolism (PE). Results - According to our study, there is a certain trend towards the development of severe CTEPH forms, depending on the following primary clinical and instrumental characteristics. The following factors have been recognized as favorable factors resulting in the incidence of milder CTEPH forms or its total absence in the long term: effective thrombolytic therapy, relative “freshness” of thrombotic masses, distal lesion level of the lower extremity veins (up to the popliteal veins inclusive), young age of patients. It is worth mentioning separately the adequate anticoagulant therapy, which is prescribed following the thrombolysis or in automedication. As a rule, patients followed two regimens of anticoagulant therapy after the thrombolytic therapy: unfractionated heparin during the first 24 hours, with the subsequent transition to warfarin, rivaroxaban immediately at the end of the thrombolysis. Two regimens of anticoagulant therapy: low molecular heparins followed by the transition to warfarin and rivaroxaban from the first days of treatment were also present when the thrombolytic therapy was not possible or not necessary. In the long term, we observed the best pulmonary artery recanalization by combination of the thrombolytic therapy and rivaroxaban, although there were patients who were not treated with the thrombolysis due to the developed allergic reaction in the massive PE, but on the top of administered rivaroxaban there was detected a full pulmonary channel permeability one year after the treatment onset. The effect of the pulmonary artery recanalization in the warfarin treatment was much weaker. Negative factors in the CTEPH development could include the proximal level of deep vein lesions, the elderly age of patients, not "fresh" thrombotic masses. After 10 days of their formation, each consecutive day affected negatively the efficiency forecast of the thrombolytic and anticoagulant therapy in terms of pulmonary artery recanalization. Conclusion - There are certain clinical and instrumental parameters that allow for a certain degree of prediction of the CTEPH development following the earlier PE, but further studies are required to have more reliable statistics.

4975Efficacy of pulmonary hypertension-targeted drugs for severe chronic thromboembolic pulmonary hypertension

Abstract Background High pulmonary vascular resistance (PVR) is a risk factor for reperfusion pulmonary edema by balloon pulmonary angioplasty (BPA). It has not been clarified whether improvement of hemodynamics by pulmonary hypertension (PH)-targeted drugs before BPA session is effective clinically. Severe chronic Thromboembolic pulmonary hypertension (CTEPH) patients have small vessel disease like pathological findings of idiopathic pulmonary arterial hypertension. Objectives The purpose of this study was to investigate the efficacy of PH-targeted drugs for patients with CTEPH before BPA. Methods This study included consecutive 147 CTEPH patients treated with PH-targeted drugs before BPA. All patients were divided into 2 groups such as severe group (PVR &gt;12.5 wood units) and non-severe group (PVR &lt;12.5 wood units). PVR were compared between baseline and after treated with PH-targeted drugs. All data were expressed by median [25thpercentile-75thpercentile]. Results The median age and male were 66 [53–74] years old and 42. Numbers of patients treated with phosphodiesterase V inhibitors, endothelin receptor antagonists and riociguat were 84 (57%), 92 (63%), and 43 (29%), respectively. PVR significantly decreased after treated with PH-targeted drugs in two groups (severe group: 16.3 [13.7–20.0] to 10.0 [7.2–13.3] wu, P&lt;0.0001; non-severe group: 6.8 [4.9–8.9] to 5.7 [3.5] to 7.8, P&lt;0.001). Changes of PVR in severe group were significantly larger than in non-severe group (−6.9 [−8.5 to −3.2] vs. −0.7 [−2.4 to 0.7], P&lt;0.0001). There was no significant difference in efficacy of BPA and numbers of dilated vessel between two groups (severe vs. non-severe group after BPA; PVR: 2.7 [1.9–3.5] vs. 2.1 [1.7–3.1] wu, P&gt;0.05; numbers of dilated vessel: 18 [14–21] vs. 16 [10–21], P&gt;0.05) Conclusions PH-targeted drugs may improve hemodynamics for severe CTEPH more effectively.

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum–maximum 26–50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

A Case of Chronic Thromboembolic Pulmonary Hypertension in a High-Altitude Dweller

Chronic hypoxia causes sustained pulmonary vasoconstriction and vascular remodeling leading to development of pulmonary hypertension in high-altitude residents. Although pulmonary hypertension is of mild to moderate degrees in most cases, some high-altitude residents may develop severe pulmonary hypertension. We report a case of a 47-year-old female highlander of Kyrgyz ethnicity who presented with exertional breathlessness and echocardiographic signs of severe pulmonary hypertension, who was diagnosed as having chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, this is the first documented case of severe CTEPH in a high-altitude dweller. This case illustrates that causes other than hypoxia may underlie and/or contribute to severe pulmonary hypertension in residents of high altitude.

Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial

Treprostinil, a prostacyclin analogue, is effective for the treatment of pulmonary arterial hypertension. However, information is scarce regarding treprostinil for treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the efficacy and safety of subcutaneous treprostinil in this setting. In this 24-week, randomised, double-blind controlled trial, we enrolled patients with CTEPH, classified as non-operable, or with persistent or recurrent pulmonary hypertension after pulmonary endarterectomy, in six European expert centres in Austria, Czech Republic, Germany, and Poland. Patients in WHO functional class III or IV with a 6-min walk distance of 150-400 m were randomly assigned at a 1:1 allocation ratio to continuous high-dose subcutaneous treprostinil (target dose around 30 ng/kg per min at week 12) or low-dose subcutaneous treprostinil (target dose around 3 ng/kg per min at week 12). The primary endpoint was the change from baseline in 6-min walk distance at week 24. All patients who received at least one dose of the study drug were included in the intention-to-treat efficacy and safety analyses based on assessment of adverse events. The trial was registered at ClinicalTrialsRegister.eu EudraCT number 2008-006441-10 and ClinicalTrials.gov, number NCT01416636. From March 9, 2009, to June 9, 2016, 105 patients were enrolled with 53 (50%) patients randomly assigned to high-dose and 52 (50%) patients to low-dose subcutaneous treprostinil. At week 24, marginal mean 6-min walk distance improved by 44·98 m (95% CI 27·52 to 62·45) in the high-dose group, and by 4·29 m (95% CI -13·34 to 21·92) in the low-dose group (treatment effect 40·69 m, 95% CI 15·86 to 65·53, p=0·0016). 12 serious adverse events were reported in ten (19%) of 52 patients from the low-dose group and 16 serious adverse events were reported in nine (17%) of 53 patients from the high-dose group. The most common treatment-related adverse events in both groups were infusion site pain and other infusion site reactions. Treatment with subcutaneous treprostinil was safe, and improved exercise capacity in patients with severe CTEPH. Subcutaneous treprostinil provides a parenteral treatment option for patients of WHO functional class III or IV and those who do not tolerate other therapies or need combination treatment. SciPharm Sàrl.

Case report: Life-saving pulmonary endarterectomy for a young female with primary antiphospholipid syndrome complicated by severe chronic thromboembolic pulmonary hypertension

Abstract Background: Prothrombotic state and impaired clot dissolution can contribute to the occurrence of chronic thromboembolic pulmonary hypertension in primary antiphospholipid syndrome. Pulmonary endarterectomy - the surgical removal of the organized thromboembolic material from the proximal pulmonary arteries - is the procedure of choice and potentially a curative option for patients with chronic thromboembolic pulmonary hypertension, including patients with antiphospholipid syndrome. We report an exceptionally severe and complicated case with favourable outcome. Case presentation: We present a case of a successful high risk pulmonary endarterectomy in a 29-year-old female with primary antiphospholipid syndrome and end-stage chronic thromboembolic pulmonary hypertension. Despite highly complicated perioperative course an impressive improvement in symptoms and functional status was achieved. Conclusion: We hope that this complicated but successfully managed case of a combination of two rare diseases will arouse earlier suspicion and timely diagnosis for such patients and will encourage physicians to promptly refer the suitable patients to a pulmonary endarterectomy team. It is important to remember that severe thrombocytopenia may occur in patients with antiphospholipid syndrome

Heart Rate and Oxygen Saturation Change Patterns During 6-min Walk Test in Subjects With Chronic Thromboembolic Pulmonary Hypertension.

The 6-min walk test (6MWT) is commonly performed to assess functional status in patients with chronic thromboembolic pulmonary hypertension. However, changes in heart rate and oxygen saturation (SpO2 ) patterns during 6MWT in patients with chronic thromboembolic pulmonary hypertension remain unclear. Thirty-one subjects with chronic thromboembolic pulmonary hypertension were retrospectively evaluated to examine the relationships between the change in heart rate (Δheart rate), heart rate acceleration time, slope of heart rate acceleration, heart rate recovery during the first minute after 6MWT (HRR1), change in SpO2 (ΔSpO2 ), SpO2 reduction time, and SpO2 recovery time during 6MWT, and the severity of pulmonary hemodynamics assessed by right heart catheterization and echocardiography. Subjects with severe chronic thromboembolic pulmonary hypertension had significantly longer heart rate acceleration time (144.9 ± 63.9 s vs 96.0 ± 42.5 s, P = .033), lower Δheart rate (47.4 ± 16.9 vs 61.8 ± 13.6 beats, P = .02), and lower HRR1 (13.3 ± 9.0 beats vs 27.1 ± 9.2 beats, P < .001) compared to subjects with mild chronic thromboembolic pulmonary hypertension. Subjects with severe chronic thromboembolic pulmonary hypertension also had significantly longer SpO2 reduction time (178.3 ± 70.3 s vs 134.3 ± 58.4 s, P = .03) and SpO2 recovery time (107.6 ± 35.3 s vs 69.8 ± 32.7 s, P = .004) than did subjects with mild chronic thromboembolic pulmonary hypertension. Multivariate linear regression analysis showed only mean pulmonary arterial pressure independently was associated with heart rate acceleration time and slope of heart rate acceleration. Heart rate and SpO2 change patterns during 6MWT are predominantly associated with pulmonary hemodynamics in subjects with chronic thromboembolic pulmonary hypertension. Evaluating heart rate and SpO2 change patterns during 6MWT may serve as a safe and convenient way to follow the change in pulmonary hemodynamics.

P2597Riociguat as a bridge therapy for balloon pulmonary angioplasty in patients with severe chronic thromboembolic pulmonary hypertension

P2597Riociguat as a bridge therapy for balloon pulmonary angioplasty in patients with severe chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension

Background and objectivePulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Material and methodsSince February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/s/cm−5, and group 2, which included the remaining 120 patients. ResultsHospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (p=0.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). ConclusionsPulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery.

Evaluation of Reperfusion Pulmonary Edema by Extravascular Lung Water Measurements After Pulmonary Endarterectomy.

Reperfusion pulmonary edema is a specific complication of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Extravascular lung water measurement may be valuable for diagnosing reperfusion pulmonary edema. The primary objective of this study was to describe and assess the clinical significance of extravascular lung water variations after pulmonary endarterectomy. Prospective observational study. Nineteen-bed cardiothoracic ICU. Consecutive patients who were hemodynamically stable after pulmonary endarterectomy were divided into two groups based on whether their preoperative pulmonary vascular resistance indicated severe or nonsevere chronic thromboembolic pulmonary hypertension (> 900 or ≤ 900 dynes·s/cm, respectively). Hemodynamic variables obtained by right heart catheterization and transpulmonary thermodilution measurements were recorded 1 hour, 1 day, and 2 days after pulmonary endarterectomy. Extravascular lung water was indexed to predicted body weight (EVLWPBW). We studied 31 patients. Overall, 26 patients (84%) experienced reperfusion pulmonary edema during the first 72 hours after pulmonary endarterectomy. EVLWPBW significantly increased between the first hour after pulmonary endarterectomy and day 2 (10.2 ± 2.6 vs 11.4 ± 3.6; p = 0.03). EVLWPBW measured at the first hour after pulmonary endarterectomy is closely associated with reperfusion pulmonary edema occurrence in the next 48 hours (area under the receiver-operating characteristics curve = 0.88 ± 0.07). EVLWPBW correlated with duration of mechanical ventilation (ρ = 0.59; p < 0.0001) and ICU stay (ρ = 0.52; p < 0.0001). Patients with severe chronic thromboembolic pulmonary hypertension (n = 15) had higher EVLWPBW values at day 2 compared with those without (n = 16) (13.2 ± 3.6 vs 9.7 ± 2.7 mL/kg; p = 0.004). Cardiac output was measured simultaneously by pulmonary artery catheter and aortic transpulmonary thermodilution on 92 occasions; agreement was good, with a bias of 0.50 ± 0.95 L/min (95% CI, -1.36-2.36). Accurate extravascular lung water measurements were obtained after pulmonary endarterectomy. Extravascular lung water may prove valuable for diagnosing reperfusion pulmonary edema after pulmonary endarterectomy and had prognostic value. Extravascular lung water values were significantly higher in patients with severe compared with nonsevere chronic thromboembolic pulmonary hypertension.

Resultados de la tromboendarterectomía pulmonar en la hipertensión pulmonar tromboembólica crónica

Background and objectivePulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Material and methodsSince February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/sec/cm−5, and group 2, which included the remaining 120 patients. ResultsHospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (P=.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). ConclusionsPulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery.