Search

BACKGROUND The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension. RESEARCH QUESTION What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects? STUDY DESIGN AND METHODS This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019. RESULTS Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001). INTERPRETATION Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.

Objectives The aim of this study was to investigate the incidence of May-Thurner anatomy (MTA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and identify its predictors. Background MTA is an anatomical variant characterized by compression of left common iliac vein by the overlying right iliac artery. Over time, this leads to venous intimal scarring, blood flow stasis, and the development of deep vein thrombosis (DVT). DVT is a known risk factor for the development of CTEPH. The prevalence of this anatomical variation in patients with CTEPH is unknown. Methods A retrospective chart review was conducted in patients referred to Temple University Hospital’s cardiac catheterization laboratory for the evaluation of CTEPH between January 2016 and June 2020. Among these patients, those who underwent invasive venography were evaluated for the presence of angiographic MTA. Multivariate regression was used to identify factors associated with presence of MTA. Results A total of 193 patients with CTEPH were referred for pulmonary angiography, of whom 148 patients underwent invasive venography. MTA was identified in 44 patients (29.7%). Factors associated with the presence of MTA were lower extremity DVT (odds ratio: 3.5; 95% confidence interval: 1.58-7.8; P = 0.002), and left lower extremity post-thrombotic syndrome (odds ratio: 2.0; 95% confidence interval: 0.98-4.1; P = 0.05). Patients with MTA were more likely to undergo pulmonary thromboendarterectomy than patients without MTA (79.5% vs 58.7%; P = 0.015). Conclusions MTA is very common in patients with CTEPH. History of lower extremity DVT and or left lower extremity post-thrombotic syndrome was associated with the presence of MTA.

Background At the University of California, San Diego, routine coronary angiography has generally been performed in men 40 years of age and older and women 45 years of age and older before pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH). The prevalence of significant coronary artery disease (CAD) in this population has not been evaluated, however, and the optimal screening strategy has not been established. This study sought to evaluate whether the current approach may be better optimized on the basis of cardiac risk factors. Methods This study included 462 consecutive patients with CTEPH who were undergoing preoperative coronary angiography for pulmonary thromboendarterectomy. Baseline demographic and medical information was recorded. Major cardiac risk factors included: diabetes, hypertension, hyperlipidemia, body mass index 25 kg/m2 or greater, tobacco use, and family history of CAD. Charts were then reviewed for presence of significant CAD and revascularization. Results Significant CAD was found in 13.4% of patients who underwent routine preoperative coronary angiography; it was present in only 5% of patients younger than 50 years of age, compared with 16% of patients 50 years old and older. No patient younger than 50 years of age without cardiac risk factors was found to have significant CAD. Furthermore, in patients younger than 50 years of age, significant CAD was found only among those with 3 or more major risk factors. Conclusions In patients younger than 50 years of age with CTEPH, the prevalence of significant CAD was low. Omitting preoperative coronary angiography in this subset of patients is reasonable when no coronary risk factors are present. Preoperative coronary angiography is warranted in individuals 50 years of age and older, as well as in those younger than 50 years who have significant risk factors for CAD.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.

Perioperative anticoagulation management for patients with heparin-induced thrombocytopenia requiring cardiopulmonary bypass and deep hypothermic circulatory arrest presents a clinical challenge. Alternative anticoagulants have been used but can cause significant postoperative bleeding. We report the successful use of cangrelor and heparin in a 30-year-old patient with severe heparin-induced thrombocytopenia undergoing urgent pulmonary thromboendarterectomy.

To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting.Parallel-arm, randomized, double-blinded, placebo-controlled trial.Academic medical center in La Jolla, California.Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy.Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU.Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both groups (placebo median 2 d [interquartile range, 2-3 d] vs ramelteon 3 d [2-5 d]; p = 0.181). Coma-free days was also similar between groups (placebo median 2 d [interquartile range, 1-3 d] vs ramelteon 3 d [2-4 d]; p = 0.210). We found no difference in ICU length of stay (median 4 d [interquartile range, 3-5 d] vs 4 d [3-6 d]; p = 0.349), or in-hospital mortality (four vs three deaths; relative risk ratio, 0.7; 95% CI, 0.2-3.2; p = 0.717), all placebo versus ramelteon, respectively.Ramelteon 8 mg did not prevent postoperative delirium in patients admitted for elective cardiac surgery.

BACKGROUND AND OBJECTIVES Atrial arrhythmias (AAs) are common after cardiac surgeries including pulmonary thromboendarterectomy (PTE). This study was done to identify patients at highest risk of developing post-PTE AA and their length of stay (LOS). METHODS We reviewed 521 consecutive patients referred to University of California San Diego (UCSD) for PTE and examined their demographics as well as their baseline pulmonary hemodynamics to determine risk factors for AA. RESULTS Overall, 24.2% of patients developed an AA after PTE. Patients who developed AA had a significantly longer Intensive Care Unit (ICU) LOS (median: 5 vs 3 days, P

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns. Objective The US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era. Methods Thirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival. Results Data from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival. Conclusions This manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States. Trial Registration ClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284 International Registered Report Identifier (IRRID) DERR1-10.2196/25397

Background Hypodense filling defects within the pulmonary veins on computed tomography described as pulmonary vein sign (PVS) have been noted in acute pulmonary embolism and shown to be associated with poor prognosis. We evaluated venous flow abnormalities in chronic thromboembolic pulmonary hypertension (CTEPH) to determine its usefulness in the computed tomography assessment of CTEPH. Methods and Results Blinded retrospective computed tomography analysis of 50 proximal CTEPH cases and 3 control groups—50 acute pulmonary embolism, 50 nonthromboembolic cohort, and 50 pulmonary arterial hypertension. Venous flow reduction was assessed by the following: (1) presence of a filling defect of at least 2 cm in a pulmonary vein draining into the left atrium, and (2) left atrium attenuation (>160 Hounsfield units). PVS was most prevalent in CTEPH. Compared with all controls, sensitivity and specificity of PVS for CTEPH is 78.0% and 85.3% (95% CI, 64.0–88.5 and 78.6–90.6, respectively) versus 34.0% and 70.7% (95% CI, 21.2−48.8 and 62.7–77.8) in acute pulmonary embolism, 8.0% and 62% (95% CI, 2.2–19.2 and 53.7–69.8) in nonthromboembolic and 2.0% and 60% (95% CI, 0.1−10.7 and 51.7−67.9) in pulmonary arterial hypertension. In CTEPH, lobar and segmental arterial occlusive disease was most commonly associated with corresponding absent venous flow. PVS detection was highly reproducible (Kappa=0.96, 95% CI, 0.90–1.01, P Conclusions PVS is easy to detect with higher sensitivity and specificity in CTEPH compared with acute pulmonary embolism and is not a feature of pulmonary arterial hypertension. Asymmetric enhancement of pulmonary veins may serve as an additional parameter in the computed tomography assessment of CTEPH and can be used to differentiate CTEPH from pulmonary arterial hypertension.

The treatment of chronic thromboembolic pulmonary hypertension has expanded considerably. The ability to endarterectomize chronic thromboembolic material, the availability of pulmonary hypertension medical therapy to treat inoperable chronic thromboembolic pulmonary hypertension and/or residual pulmonary hypertension, and the rebirth of pulmonary balloon angioplasty have changed the management landscape. Patient selection requires a multidisciplinary evaluation at an experienced center. What is inoperable chronic thromboembolic pulmonary hypertension to one group may be operable chronic thromboembolic pulmonary hypertension to another. The ultimate challenge then becomes which intervention provides the optimal long-term outcome for any individual patient.

The past four decades have witnessed considerable advancements in our understanding of the pathophysiology, and the diagnosis and treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The development of an effective surgical treatment for this disease has been one of the most remarkable achievements to realize a cure for many afflicted with this form of pulmonary hypertension. For those patients with inoperable CTEPH, the past 8 years have been similarly marked by new developments. Studies demonstrating effective pulmonary hypertension-targeted medical therapy and the advancement of balloon pulmonary angioplasty (BPA) now provide patients who are not candidates for surgery beneficial treatment options. However, long-term efficacy of these treatment modalities and the selection of patients appropriate for BPA are topics of ongoing debate and research. This report provides an overview of the current, state-of-the-art therapeutic approach to the CTEPH patient.

Uterine fibroids have been described as an associate to acute venous thromboembolism (VTE), with case reports showing an association between large uterine fibroids, acute deep venous thrombosis (DVT), and acute pulmonary embolism (PE). However, there is little known about the association or causation between uterine fibroids, chronic thromboembolic disease (CTED), and chronic thromboembolic pulmonary hypertension (CTEPH). We report on six women with uterine fibroids and CTEPH, as well as one woman with CTED, all of whom presented with exertional dyspnea, lower extremity swelling, and in the cases of CTEPH, clinical, echocardiographic, and hemodynamic evidence of pulmonary hypertension and right heart failure. Compression of the pelvic veins by fibroids was directly observed with invasive venography or contrast-enhanced computed tomography in five cases. All seven women underwent pulmonary thromboendarterectomy (PTE) followed by marked improvement in functional, clinical, and hemodynamic status.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disease with significant morbidity. It is a result of an alternate natural history in which there is limited resolution of thromboemboli with pulmonary artery obstruction leading to pulmonary hypertension (PH). CTEPH requires a thorough clinical assessment including pulmonary hemodynamics and radiologic evaluation in addition to consultation with an expert center. Surgical intervention remains the optimal management strategy. Select patients may be candidates for catheter-based intervention with balloon pulmonary angioplasty in centers with clinical expertise. Inoperable patients or those with post-intervention PH are treated with pulmonary hypertension-targeted medical therapy.

Background: Left ventricular dyssynchrony has been studied extensively, but this is not the case with right ventricular (RV) dyssynchrony. Our aim was to investigate RV dyssynchrony through 2D speckle strain imaging in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE).Methods: We measured 2D peak RV strain (%) of the RV free-wall and time to peak strain (ms) of its three freewall segments (base, mid, and apex) in 127 consecutive CTEPH patients (51 ± 14 years, 59% female) with adequate images pre- and post-PTE. RV strain was calculated using Epsilon Imaging EchoInsight® software. RV dyssynchrony was measured using two methods: the standard deviation of peak systolic strain and the standard deviation of time (ms) to peak strain (RVDT) between the three RV free-wall segments.Results: Mean RV free wall strain did not change significantly after PTE (−11.4 ± 5.7 to −11.2 ± 5.6%, p = 0.67). However, RV dyssynchrony improved dramatic...

There are several mimics of chronic thromboembolic disease and CTEPH. While screening studies such as lung scintigraphy can direct attention to the pulmonary vessels as the source of a patient’s clinical presentation, there are a number of disease states that result in these nonspecific radiographic findings. Historical clues, subtle pulmonary angiographic findings and advanced pulmonary vascular and lung imaging can be critically important in establishing the correct diagnosis, as illustrated in the case presented here.

The diagnosis of pulmonary veno-occlusive disease can be very challenging. Although lung ventilation-perfusion scintigraphy is typically normal in this disease, an abnormal scan can be observed in patients with PVOD. This case presentation illustrates this point, and how the abnormal lung scan and pulmonary angiogram was initially interpreted as CTEPH in this 23 year old male.

That CT angiography demonstrates evidence for chronic thrombus while the perfusion pattern on lung scintigraphy is normal can be readily explained. This case will demonstrate this “discrepancy” and underscores the value of a normal VQ scan in ruling out operable chronic thromboembolic disease.

Treatment options for patients with inoperable chronic thromboembolic pulmonary hypertension have expanded with the availability of balloon pulmonary angioplasty and pulmonary hypertension targeted medical therapy. Often, both options are appropriate for the provision of care for those patients who are not deemed candidates for PTE surgery. As illustrated by this case, the task of selecting patients suitable for balloon pulmonary angioplasty can be a difficult one, typically requiring input from diagnosticians, radiologists, and surgeons experienced in the evaluation and treatment of patients with CTEPH.

While pulmonary hypertension, an abnormal VQ scan and angiographic evidence of thrombus in the pulmonary arteries are necessary to diagnose chronic thromboembolic pulmonary hypertension, an atrial septal defect with Eisenmenger’s syndrome may present with similar findings. Clues to the presence of an ASD include digital clubbing and scintigraphic evidence of right-to-left shunt with uptake of technetium macro aggregated albumin seen in the brain and kidneys. An echocardiogram with bubble study can also demonstrate a right-to-left shunt. Patients with Eisenmenger’s syndrome should have pulmonary hypertension medically managed. There is no benefit to pulmonary thromboendarterectomy for chronic in situ thrombosis frequently seen in these patients.

The importance of establishing the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) centers on the observation that with a thromboendarterectomy, this pulmonary vascular disease is potentially curable. As a result, a careful assessment of patients at-risk for or suspected of having CTEPH is essential, and this case presentation illustrates an appropriate approach for such an evaluation.

Pulmonary thromboendarterectomy remains the best option for patients with chronic thromboembolic pulmonary hypertension as a potential cure for their disease. With advances in this surgical procedure, endarterectomy of the more distal pulmonary vascular bed has become possible. This case provides an example of the clinical benefits that can be achieved with distal vessel thromboendarterectomy.

There are a number of clinical conditions that mimic the radiographic findings in CTEPH, but few are as difficult to distinguish from CTEPH as pulmonary arteritis. However, as the presented case will demonstrate, there are often hints in the evaluation of patients with pulmonary hypertension to suggest large vessel arteritis as the principal diagnosis.

Perfusion defects on standard lung scintigraphy can be due to many causes, though typically from occlusion or partial obstruction of the pulmonary arteries. This case presentation highlights that outflow obstruction due to large pulmonary venous disease may result in perfusion abnormalities, and should be considered in the differential when a clinician is presented with an abnormal lung ventilation-perfusion scan.

The transition from acute to chronic thromboembolic disease can occur to an unpredictable degree in patients who survive an acute pulmonary embolism. In the vast majority of such patients on anti-thrombotic therapy, near complete resolution of the thrombus occurs. In 2–3% of patients, chronic thromboembolic pulmonary hypertension will develop. However, in an unknown percentage of pulmonary embolic survivors, organized thrombotic residua can involve enough of the pulmonary vascular bed to cause cardiopulmonary symptoms in the absence of pulmonary hypertension or right heart dysfunction. This is referred to as chronic thromboembolic disease or CTED, and the case presentation to follow illustrates some of challenges in treatment recommendations for this unique disease.

Establishing the diagnosis and operability of chronic thromboembolic disease in patients with pulmonary hypertension are the critical first steps in determining surgical candidacy for thromboendarterectomy. However, whether or not a CTEPH patient is ultimately a surgical candidate requires a complete overview of comorbidities, a realistic prediction that a PTE will result in a clinical benefit, and patient acceptance. This case presentation explores the decision-making challenges often faced during an evaluation of patients with chronic thromboembolic disease and multiple comorbidities.

The distinction between acute and chronic thromboembolic disease is frequently difficult at the time of initial presentation. However, the importance in making this distinction is underscored by the considerable differences in treatment strategies required for these clinical problems. Not only are there historical clues, but an understanding of the disparate radiographic appearance between acute and chronic thrombi can often prevent an inappropriate intervention. This case presentation highlights these important considerations.

A case of apparent chronic thromboembolic pulmonary hypertension that surprisingly exhibited metastatic squamous cell carcinoma embedded in the organized thrombus endarterectomized from the proximal pulmonary vessels.

Patients with distal CTEPH remain among the most challenging to manage. This case illustrates the importance of screening all pulmonary hypertensive patients for CTEPH, and the value of correctly identifying patients with distal vessel chronic thromboembolic disease where a cure with thromboendarterectomy is feasible.

Lung scintigraphy is an invaluable screening tool in the evaluation of the pulmonary hypertensive patient. The absence of perfusion defects is properly interpreted to exclude occlusive pulmonary vascular disease such as CTEPH. However, unmatched perfusion defects are due to a number of disease states, and as illustrated with this presented case, extensive precapillary, small vessel pulmonary vascular disease needs to be considered among the possibilities.

Large-vessel pulmonary artery sarcomas are rare tumors of the pulmonary vasculature, accounting for only a fraction of primary lung cancers and with a very poor prognosis. They arise proximally from within the pulmonary artery and spread within the arterial lumen, causing obstruction of the vasculature that may result in right ventricular failure. Although they may have a similar presentation to chronic thromboembolic pulmonary disease and CTEPH, there are subtle indicators in history and imaging that can help with their differential diagnosis, with the confirmation usually resulting from tissue biopsy. This case presentation focuses on this CTEPH mimic.

Perfusion defects on ventilation-perfusion scan and eccentric thrombus lining major pulmonary vessels on CT pulmonary angiography in a patient with severe chronic obstructive airways disease and pulmonary hypertension may not represent CTEPH. This case presentation emphasizes the diagnostic treatment challenges in an emphysema patient with CT evidence for chronic thrombus.

Main pulmonary artery occlusion from chronic thromboembolic disease can rarely be the cause for non-perfusion of an entire lung. Careful evaluation of alternative and more common causes for this finding is essential. For those patients with chronic thromboembolic disease, thromboendarterectomy may result in lung reperfusion. However, the achievement of this outcome may be impacted by the extent of collateral systemic blood flow and duration of main pulmonary artery occlusion.

Chronic thromboembolic disease can lead to significant exercise limitations even in the absence of pulmonary hypertension. The decision to proceed with pulmonary thromboendarterectomy is complex, but as in this case, can lead to significant improvements in lung perfusion and exercise tolerance. Though speculative, intervention at this stage of the disease may also prevent the development of significant pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism that is associated with abnormalities in haemostasis. We investigated the ADAMTS13–von Willebrand factor (VWF) axis in CTEPH, including its relationship with disease severity, inflammation, ABO groups and ADAMTS13 genetic variants. ADAMTS13 and VWF plasma antigen levels were measured in patients with CTEPH (n=208), chronic thromboembolic disease without pulmonary hypertension (CTED) (n=35), resolved pulmonary embolism (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68). CTEPH genetic ABO associations and protein quantitative trait loci were investigated. ADAMTS13–VWF axis abnormalities were assessed in CTEPH and healthy control subsets by measuring ADAMTS13 activity, D-dimers and VWF multimeric size. Patients with CTEPH had decreased ADAMTS13 (adjusted β −23.4%, 95% CI −30.9– −15.1%, p, The ADAMTS-13–VWF axis is dysregulated in chronic thromboembolism with and without pulmonary hypertension and is implicated in the pathogenesis http://ow.ly/J9SC30nh5T0

Right ventricular function is impaired in chronic thromboembolic pulmonary hypertension (CTEPH). Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) have been shown to help assess right ventricular function in pulmonary hypertension. Our goal was to (1) assess TAPSE and RVFAC before and after PTE, and (2) assess correlation of these variables with right heart catheterization data and PVR.We evaluated 67 consecutive patients with CTEPH for pulmonary thromboendarterectomy (PTE). Of these 67 patients, 48 were deemed surgical candidates. Preoperative right heart catheterization was performed within 1.3±1.2 days of the preoperative echocardiogram. All postoperative right heart catheterizations were performed on the first postoperative day.TAPSE dropped from 18±6 to 10±3 mm after PTE (P.0001). RVFAC remained the same (25%±10% vs 30%±12%). Mean pulmonary artery (mPAP) pressure dropped from 45±12 to 28±6 mm Hg after PTE, and pulmonary vascular resistance (PVR) decreased from 757±406 to 306±147 dyne-s/cmIn patients with CTEPH, TAPSE paradoxically decreased by 50% early after PTE. TAPSE correlated inversely with PVR prior to PTE, but this correlation was lost completely after PTE. Thus, despite the immediate and marked decrease in afterload postoperatively, TAPSE did not improve; thus, TAPSE cannot be used as an early marker for surgical success.

Chronic thromboembolic pulmonary hypertension is a progressive and life-threatening condition that is believed to be related to inadequate dissolution of acute pulmonary thromboemboli, followed by fibrotic organization. Without appropriate treatment, progressive pulmonary hypertension, right ventricular failure, and death may occur. While the disorder was initially described nearly a century ago in autopsy studies, antemortem diagnosis became feasible with the advent of cardiac catheterization and angiography techniques in the 1940s, while surgical thromboendarterectomy was not attempted until the 1960s. However, this procedure initially had high mortality rates until refinements in management and surgical techniques resulted in much improved outcomes starting in the 1980s. Many questions remain about the pathophysiology and epidemiology of this condition, with unclear contributions of genetics and environmental exposures. The optimal approach to diagnosis also continues to evolve, with improvements in preoperative imaging and hemodynamic assessment. Treatment of chronic thromboembolic pulmonary hypertension has not remained static, as surgical techniques continue to improve and newer pharmacological treatments and percutaneous catheter-based interventions may play therapeutic roles in selected patients. This is the introductory article of a series that provides a state-of-the-art review of chronic thromboembolic pulmonary hypertension.

Pulmonary hypertension due to chronic thromboembolic disease is potentially curable with pulmonary thromboendarterectomy surgery. As a result, it is important for clinicians to recognize and appropriately diagnose this form of pulmonary hypertension. Advances in this field with changes in surgical technique, the availability of PH-targeted medical therapy for select patient subgroups, and the development of balloon pulmonary angioplasty have broadened therapeutic options for patients. This review will examine what is known about the epidemiology and medical conditions placing patients at risk of developing this disease, will present an approach to evaluation of patients with suspected chronic thromboembolic disease, and will describe the surgical and non-surgical management of this unique patient population.

Background Post-operative atrial arrhythmias (POAA) after cardiac surgery are common and known to prolong hospital length of stay (LOS), but have been reported grouping atrial fibrillation (POAF), atrial flutters (AFL), and atrial tachycardias (AT). The impact of POAA vs. specifically POAF on intensive care unit time (ICUT) and hospital LOS after pulmonary thromboendarterectomy surgery (PTE) remains unknown. Objective To determine the impact of POAA and POAF on ICUT and hospital LOS after PTE. Method We identified consecutive patients undergoing PTE at our medical center from June 2013 to March 2020. After assessing baseline patient characteristics, we compared ICUT and LOS in patients with and without POAA and POAF after PTE. Results A total of 224 patients underwent PTE. POAA occurred in 31% (n = 68), of which 71% (n = 48) were POAF. Patients who developed POAA were older on average (63.5 vs. 51.5 years, p Conclusion In an adjusted analysis, in patients undergoing PTE, neither development of POAA nor specifically POAF were associated with increased ICUT. However, both POAA and POAF were associated with longer hospital LOS, denoting that POAA and POAF prolong hospitalization outside the ICU.

This study aimed to validate an algorithm developed to identify chronic thromboembolic pulmonary hypertension (CTEPH) among patients with a history of pulmonary embolism. Validation was halted because too few patients had gold-standard evidence of CTEPH in the administrative claims/electronic health records database, suggesting that CTEPH is underdiagnosed.

Objectives This study aimed to identify the prevalence of cardiac implantable electronic devices (CIEDs) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to describe the associated disease burden. Background CTEPH is a debilitating disease, now potentially curable with pulmonary thromboendarterectomy (PTE). The contribution of CIEDs to thrombosis in this patient population has not been previously studied. Methods The charts of 982 CTEPH patients, who underwent PTE between January 1, 2009, and December 31, 2015 at University of California-San Diego (UCSD) Medical Center, were reviewed for pacemakers or implantable cardioverter defibrillators (ICDs) implanted before surgery. Results Among 982 CTEPH patients who underwent PTE, 14 had pacemakers and 3 had ICDs, giving 17 CIEDs and a prevalence of 1.7%. Of these 17 CIEDs, 6 devices were extracted intraoperatively, and 5 of 6 devices were replaced with epicardial leads. Furthermore, of the 950 patients classified by intraoperative UCSD level, 12 of 17 (70.6%) patients with CIEDs had distal disease versus 241 of 933 (25.8%) patients without CIEDs (p = 0.0002). The prevalence of known venous thromboembolism (VTE) was 50% in CIED patients compared with 78.6% in patients without CIEDs (p = 0.018). Conclusions At 1.7%, the prevalence of CIEDs in the PTE population was higher than previously reported values, which estimated CIED prevalence between 0.16% and 0.47% in the general population. Moreover, CTEPH patients with CIEDs were more strongly associated with distal disease burden and less likely to have had previous VTE, which suggested that CIEDs may be a nidus for small clots that embolize distally in the pulmonary vasculature.

Reperfusion lung injury is a postoperative complication of pulmonary thromboendarterectomy that can significantly affect morbidity and mortality. Studies in other postoperative patient populations have demonstrated a reduction in acute lung injury with the use of a low-tidal volume (Vt) ventilation strategy. Whether this approach benefits patients undergoing thromboendarterectomy is unknown.We sought to determine if low-Vt ventilation reduces reperfusion lung injury in patients with chronic thromboembolic pulmonary hypertension undergoing thromboendarterectomy.Patients undergoing thromboendarterectomy at one center were randomized to receive either low (6 ml/kg predicted body weight) or usual care Vts (10 ml/kg) from the initiation of mechanical ventilation in the operating room through Postoperative Day 3. The primary endpoint was the onset of reperfusion lung injury. Secondary outcomes included severity of hypoxemia, days on mechanical ventilation, and intensive care unit and hospital lengths of stay.A total of 128 patients were enrolled and included in the analysis; 63 were randomized to the low-Vt group and 65 were randomized to the usual care group. There was no statistically significant difference in the incidence of reperfusion lung injury between groups (32%, n=20 in the low-Vt group vs. 23%, n=15 in the usual care group; P=0.367). Although differences were noted in plateau pressures (17.9 cm H2O vs. 20.1 cm H2O, P0.001) and peak inspiratory pressures (20.4 cm H2O vs. 23.0 cm H2O, P0.001) between the low-Vt and usual care groups, respectively, mean airway pressures, PaO2/FiO2, days on mechanical ventilation, and ICU and hospital lengths of stay were all similar between groups.In patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy, intra- and postoperative ventilation using low Vts (6 mg/kg) compared with usual care Vts (10 mg/kg) does not reduce the incidence of reperfusion lung injury or improve clinical outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT00747045).

This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion.

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is an infrequent but important complication of acute pulmonary embolism (PE). Thrombophilias and non-O blood groups are genetic risk factors for venous thromboembolism (VTE), however they are not independently associated with CTEPH. Identifying genetic risk factors for CTEPH would provide important insights into pathobiology and might allow risk-stratification following PE. We undertook a genome-wide association study (GWAS) in CTEPH to identify novel disease loci. Methods To date, 1457 Caucasian CTEPH patients were enrolled from 10 European and US Centres and compared to 1536 healthy Caucasian controls from the Wellcome Trust Case Control Consortium. Genotyping was performed using the HumanOmniExpressExome-8 array. Quality control criteria and statistical analysis are summarised in figure 1. Results 1250 CTEPH cases, 1492 controls and 7 million single-nucleotide polymorphisms (SNPs) were included after quality control exclusions. Two loci, in chromosomes 4 and 9 were significantly associated with CTEPH (figure 1). The lead SNP in chr9 (rs532436, OR=2.38, p=4.6x10-32) is highly correlated with the tagging SNP for the A1 blood group (rs507666, R2=0.99). Reconstructing genetic ABO groups confirmed an over-representation of the A1A1 group in CTEPH compared to controls (7% vs. 2.9%, OR 4.5). Additionally, there were 11 significant SNPs in the chr9 ADAMTS13 gene locus that is moderately correlated with ABO (R2=0.33). The lead SNP in chr4 (rs13130318, OR=1.4, p=5.6x10-8) is highly correlated with a missense variant in FGG (rs6050, R2=0.89) associated with decreased fibrinogen protein and increased resistance to fibrinolysis in CTEPH. There were no associations at the F5 locus, which is highly significant in VTE. Conclusions We report the first GWAS in CTEPH, identifying at least 2 genetic loci associated with the disease. The ABO association is driven by the A1 blood group and represents the largest population attributable genetic risk factor for CTEPH, which is higher than previously reported for VTE. The potential ADAMTS13 association is a plausible biological candidate, and further work will establish whether it is independent from ABO. The lack of associations with other loci found in VTE suggests that ABO might have a pathobiological role in CTEPH in addition to its contribution to VTE.

Although there are several iterations of the same theme, Albert Einstein once proclaimed, “The more I learn, the more I realize how much I don’t know.” An interpretation of this notion is that each step forward in discovery simply leads to more questions to answer. The expanding experience with balloon pulmonary angioplasty worldwide in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) is reminiscent of Einstein’s assertion. In this month’s issue of Circulation: Cardiovascular Quality and Outcomes , Ogawa et al1 report the combined outcomes from 7 institutions in Japan performing balloon pulmonary angioplasty on patients with inoperable CTEPH. And although the information provided in this article is of considerable value, many unanswered questions remain. See Article by Ogawa et al The aggregate data presented in this multicenter Japanese balloon pulmonary angioplasty (BPA) registry provides a clearer characterization of patients undergoing this intervention—80% were female, medical conditions previously reported to be associated with CTEPH were uncommon, thrombophilic disorders were seen in 8.8% of patients, only 15.3% of patients had a prior episode of acute pulmonary embolism, and 34.7% were with a deep venous thrombosis history. This patient phenotype is distinctly different from that reported in large series of CTEPH patients where the male to female ratio is nearly even and a much higher percentage of patients having been identified as experiencing a previous pulmonary embolic event.2 This raises the issue as to whether the patient type is distinct in this series and, as a consequence, whether the reported outcomes are transferable to other BPA-experienced centers. It might be argued that the patient characteristics in the Japanese Registry may be reflective of those at risk for developing inoperable chronic thromboembolic disease. However, published information from several European BPA centers are more …