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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.

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.

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 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.

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...

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.

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.

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.

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 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.

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.

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.

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.

Background Obesity is a common comorbidity of patients with chronic thromboembolic pulmonary hypertension referred for pulmonary thromboendarterectomy, yet the effect of obesity on pulmonary thromboendarterectomy outcomes has not been well described. Methods We conducted a retrospective cohort study in which 476 consecutive operations over a 3.5-year period were examined to determine the effects of obesity on outcomes. Patients were grouped into four categories based on body mass index (BMI): less than 22 kg/m 2 , 22 to 30 kg/m 2 , 30 to 40 kg/m 2 , and more than 40 kg/m 2 . Results There were important differences in baseline pulmonary hemodynamics, with obese patients having significantly lower pulmonary vascular resistances than nonobese patients. All patients achieved a significant reduction in pulmonary vascular resistance, although the improvement was greatest in the lower BMI groups. The overall in-hospital mortality was 0.8%, and there were no differences in risk among BMI groups. Among the BMI groups, there were no differences in incidence of postoperative complications, including atrial fibrillation (overall 24.8%), reperfusion lung injury (overall 23.1%), and surgical site infection (overall 4.4%) or in median lengths of stay (including ventilator days, intensive care unit days, and postoperative length of stay). Conclusions Pulmonary thromboendarterectomy outcomes have continued to improve, and this surgery can safely be completed in obese patients, previously deemed to be at high risk for poor outcomes.

Bronchopulmonary collateral vasculature is a significant source of systemic blood flow in patients with chronic thromboembolic pulmonary hypertension (CTEPH).1 We present 2 cases of coronary artery-to-pulmonary artery (PA) collateral vessels, which have not been previously described in patients with CTEPH. A 40-year-old man with a history of deep venous thrombosis after parotidectomy for a benign lesion, recurrent strokes, and right-sided pulmonary embolism was evaluated for 5 years of progressive exertional dyspnea and suspected CTEPH. He had no known hereditary thrombophilia. Preoperative ventilation–perfusion scintigraphy demonstrated absent perfusion to the right lung and small defects in the left lower lobe (Figure 1). Pulmonary angiography confirmed occlusion of the proximal right PA with no distal flow (Figure 2; Movie I in the Data Supplement). His mean PA pressure was 35 mm Hg, pulmonary vascular resistance was 511 dyne/s per cm5, and cardiac index was 2.3 L/min per m2. Coronary angiography revealed a 4.6-mm diameter corkscrew vessel arising from the left circumflex artery and traveling to the right lung (Figure 3; Movie II in the Data Supplement). He had no significant coronary artery disease. The patient underwent bilateral pulmonary thromboendarterectomy (PTE; Figure 4), during which a small atrial septal defect was found and repaired. Collaterals were noted throughout the mediastinum, particularly around the aorta traversing toward the right lung and directly penetrating the right main PA. Final mean PA …

Background Right ventricular (RV) function is significantly impaired in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Two-dimensional speckle tracking RV strain and strain rate are novel methods to assess regional RV systolic function in CTEPH patients before and after pulmonary thromboendarterectomy (PTE). Our goal was to (1) assess baseline longitudinal strain and strain rate of the basal RV free wall in CTEPH and (2) measure early changes in RV strain and strain rate after PTE. Methods We performed echocardiography on 30 consecutive patients with CTEPH referred for PTE with adequate pre- and post-PTE strain imaging. Strain and strain rate were assessed 6.4 ± 4.5 days before and 9.1 ± 3.9 after PTE. Results Basal RV free wall strain and time to peak strain—but not basal RV strain rate and time to peak strain rate—changed significantly after PTE. Unexpectedly, basal RV strain became less negative, from −24.3% to −18.9% after PTE (P = 0.005). Time to peak strain decreased from 356 to 287 msec after PTE (P

UNLABELLED The ratio of tricuspid regurgitation velocity divided by the velocity-time integral of right ventricular outflow tract pulsed-wave Doppler tracing (TRV/VTI(RVOT) ) has been used to estimate pulmonary vascular resistance (PVR). However, this method has not been validated in chronic thromboembolic pulmonary hypertension (CTEPH). We assessed the utility of TRV/VTI(RVOT) in patients with CTEPH and PVR from 2 to 20 WU. All had right heart catheterization (RHC) within 2 days of echocardiography. TRV/VTI(RVOT) was calculated and RHC-derived pressures, PVR, and cardiac outputs were recorded. Mean pulmonary artery pressure was 47 ± 12 mmHg, cardiac output: 4.2 ± 1.1 L/min, PVR: 9 ± 4 WU, right atrial pressure: 12 ± 6 mmHg. Mean VTI(RVOT) was 13 ± 5 cm; mean TRV was 4.2 ± 0.8 m/s, mean tricuspid regurgitation severity was 2.5 ± 0.8 (1 = trace, 2 = mild, 3 = moderate, 4 = severe). Regression analysis demonstrated a correlation between RHC PVR and TRV/VTI(RVOT) : PVR = 19.4 × (TRV/VTI(RVOT) ) + 2.4 (r = 0.74, P < 0.001). However, Bland-Altman analysis found a poor degree of agreement between echo-derived PVR and RHC PVR. We also studied 28 patients with non-CTEPH pulmonary hypertension. Similar analysis revealed a regression equation of PVR = 20.1 × (TRV/VTIR(RVOT) ) + 0.3 (r = 0.57, P < 0.01). CONCLUSION TRV/VTI(RVOT) is only marginally useful for estimating PVR in CTEPH (r = 0.74). Moreover, the regression equation in CTEPH differs significantly from previous studies in pulmonary hypertension. Reasons for this may include the markedly elevated PVR levels in this population and specific effects on VTI(RVOT) from CTEPH.

Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than 25 mm Hg. Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as pulmonary hypertension in the presence of an organized thrombus within the pulmonary vascular bed that persists at least 3 months after the onset of anticoagulant therapy. Because CTEPH is potentially curable by surgical endarterectomy, correct identification of patients with this form of pulmonary hypertension and an accurate assessment of surgical candidacy are essential to provide optimal care. Patients most commonly present with symptoms of exertional dyspnea and otherwise unexplained decline in exercise capacity. Atypical chest pain, a nonproductive cough, and episodic hemoptysis are observed less frequently. With more advanced disease, patients often develop symptoms suggestive of right ventricular compromise. Physical examination findings are minimal early in the course of this disease, but as pulmonary hypertension progresses, may include nonspecific finding of right ventricular failure, such as a tricuspid regurgitation murmur, pedal edema, and jugular venous distention. Chest radiographs may suggest pulmonary hypertension, but are neither sensitive nor specific for the diagnosis. Radioisotopic ventilation-perfusion scanning is sensitive for detecting CTEPH, making it a valuable screening study. Conventional catheter-based pulmonary angiography retains an important role in establishing the presence and extent of chronic thromboembolic disease. However, computed tomographic and magnetic resonance imaging are playing a growing diagnostic role. Innovative technologies such as dual-energy computed tomography, dynamic contrast-enhanced magnetic resonance imaging, and optical coherence tomography show promise for contributing diagnostic information and assisting in the preoperative characterization of patients with CTEPH.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially curable disease when treated with pulmonary thromboendarterectomy (PTE). However, even at experienced surgical centers, nearly one-third of patients with CTEPH will be deemed inoperable for reasons including distal disease, comorbidities, or out-of-proportion pulmonary hypertension. It is in these patients with inoperable CTEPH that pulmonary hypertension (PH)-targeted medical therapy and balloon pulmonary angioplasty have potential therapeutic value. Previous unblinded cohort trials have assessed PH-targeted medical therapy in various subpopulations of CTEPH patients using epoprostenol, treprostinil, sildenafil, bosentan, and iloprost, each demonstrating measurable pulmonary hemodynamic effects. However, riociguat, a soluble guanylate cyclase stimulator, is the first FDA-approved therapy for inoperable CTEPH to demonstrate both an improvement in functional capabilities (6-minute walk time) as well as significant gains in secondary pulmonary hemodynamic end points in a large placebo-controlled trial. Balloon pulmonary angioplasty is an interventional procedure using telescoping catheters placed in the pulmonary arteries, through which wires and balloons are used to mechanically disrupt chronic clot material and relieve pulmonary vascular obstruction. Contemporary case series from multiple centers worldwide have demonstrated pulmonary hemodynamic improvement with this approach. As a result of these advances, patients with inoperable CTEPH who had few options as recently as 5 years ago now have alternatives with emerging evidence of therapeutic efficacy.

Over the past 4 decades, chronic thromboembolic pulmonary hypertension has evolved from an autopsy curiosity to a potentially correctable form of pulmonary hypertension. Advances in surgical techniques along with the introduction of pulmonary hypertension disease-modifying therapies provide a therapeutic option for the majority of patients afflicted with the disease. Approximately 5,000 thromboendarterectomy procedures have now been performed worldwide with mortality rates reported by established programs experienced in the management of this disease process falling to a range of 4 to 7%. A mortality rate of 1.3% has been reported in patients at low risk based on their preoperative hemodynamic profile. After a successful pulmonary thromboendarterectomy, substantial improvement and often normalization can be achieved in right ventricular function, gas exchange, exercise capacity, and quality of life. For patients not candidates for thromboendarterectomy, or for those with persistent post-thromboendarterectomy pulmonary hypertension, disease-modifying medical therapies have been demonstrated to stabilize and improve pulmonary hemodynamics, albeit not to the same extent as primary thromboendarterectomy. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options. Additional research is necessary to more accurately predict postoperative hemodynamic outcome and to define the optimal therapeutic approach, especially in patients with involvement of the distal vasculature.

Objectives The purpose of this study was to investigate the cause of abnormal left ventricular (LV) Doppler diastolic filling characteristics in chronic thromboembolic pulmonary hypertension (CTEPH). Background In CTEPH, LV diastolic function often appears abnormal. It is unclear whether this “impaired relaxation” (E Methods We studied 61 patients with an E Results After PTE, mitral E velocity increased (from 54 ± 16 cm/s to 81 ± 20 cm/s, p m ) did not change after PTE (8.0 ± 3.1 cm/s to 8.1 ± 2.0 cm/s, p = ns), whereas the velocity of the lateral mitral annulus increased (9.3 ± 3.2 cm/s to 11.8 ± 3.1 cm/s, p Conclusions The results of this study strongly suggest that the impaired relaxation pattern observed in patients with CTEPH is not solely the result of geometric effects of RV enlargement and LV chamber distortion but is caused in large part by low LV preload and relative underfilling.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) often have substantial right ventricular dysfunction. The resulting low cardiac index might predispose to sleep disordered breathing (SDB) by increasing ventilatory instability. The prevalence of SDB and potential association with impaired cardiac index was examined in patients with CTEPH. Patients referred for evaluation for pulmonary thromboendarterectomy surgery were recruited. Subjects underwent a sleep study, unless already using positive airway pressure therapy. Hemodynamic data were obtained from contemporaneous right-sided cardiac catheterization. A total of 49 subjects were included. SDB-defined as ongoing positive airway pressure use or apnea-hypopnea index (AHI) ≥5/h-was found in 57% of subjects. SDB was generally mild in severity, with respiratory events mainly consisting of hypopneas. Cardiac index was found to be significantly lower in subjects with SDB than those without (2.19 vs 2.55L/min/m(2); p= 0.024), whereas no differences were observed in other characteristics. Additionally, cardiac index was independently predictive of AHI. In a subgroup of subjects with an elevated percentage of central events, both cardiac index and lung to finger circulation time correlated with AHI. In conclusion, SDB is prevalent in patients with CTEPH and might decrease with treatments that improve cardiac index.

Although acute pulmonary embolism is epidemiologically associated with chronic thromboembolic pulmonary hypertension, the factors responsible for resistance to thrombolysis and a shift toward vascular remodeling within the pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension are unknown.Determine whether fibrin from patients is more resistant to plasmin-mediated lysis than fibrin from healthy control subjects.Fibrinogen purified from patients and control subjects was used to prepare fibrin clots, which were subsequently digested with plasmin for various periods of time. The degradation of the alpha-, beta-, and gamma-chains of fibrin and the appearance of peptide fragments over time were assessed by polyacrylamide gel electrophoresis and Western blotting.Densitometry of Coomassie-stained gels revealed significantly slower cleavage of all three polypeptide chains of fibrin from patients compared with control subjects (p0.05). In particular, release of N-terminal fragments from the beta-chain of fibrin, which promote cell signaling, cell migration, and angiogenesis, was retarded in patients compared with control subjects (p0.01).The relative resistance of patient fibrin to plasmin-mediated lysis may be due to alterations in fibrin(ogen) structure affecting accessibility to plasmin cleavage sites. The persistence of structural motifs of fibrin, such as the beta-chain N-terminus, within the pulmonary vasculature could promote the transition from acute thromboemboli into chronic obstructive vascular scars.

Pathophysiological findings in chronic thromboembolic pulmonary hypertension (CTEPH) have suggested that a secondary small vessel arteriopathy may contribute to the haemodynamic impairment observed in these patients. It was hypothesised that this element of the elevated vascular resistance may be responsive to continuous intravenous epoprostenol therapy. Retrospectively, the clinical and haemodynamic responses to continuous intravenous epoprostenol were evaluated in nine CTEPH patients who subsequently underwent pulmonary thromboendarterectomy (PTE). Cardiopulmonary haemodyamics were determined prior to the initiation of epoprostenol, while on epoprostenol, prior to PTE, and after PTE. Six patients, treated for 2-26 months prior to PTE, experienced either clinical stability or improvement that was associated with a mean reduction in pulmonary vascular resistance (PVR) of 28% (median 33%,,, range 0-46%). Three patients, treated for 3-9 months, experienced clinical deterioration during epoprostenol administration, with a significant increase in PVR in two patients. Subsequent PTE resulted in a highly significant improvement of cardiac index, mean pulmonary artery pressure and total pulmonary resistance. To conclude, selected patients with chronic thromboembolic pulmonary hypertension may benefit clinically and haemodynamically from continuous intravenous epoprostenol treatment prior to pulmonary thromboendarterectomy. Factors predictive of a beneficial response, and whether this intervention influences either morbidity or mortality associated with pulmonary thromboendarterectomy, remain to be established

Balloon angioplasty and stent placement for pulmonary arterial stenoses in children are well-established therapies. In contrast, management of isolated peripheral pulmonary arterial stenoses in adults remains relatively unexplored. Four women (ages 18-63 years) with multiple discrete intralobar pulmonary arterial stenoses were treated with balloon angioplasty. Initially, 4-5 stenoses were dilated in each patient. The mean minimum diameter of the stenoses increased from 1.3 to 3.1 mm (P < 0.001), and the mean ratio of right ventricular to aortic systolic pressure decreased from 0.92 to 0.62 (P < 0.05). Each patient had marked symptomatic improvement. However, three patients developed recurrence of symptoms 4-24 months after angioplasty, and two had angiographic evidence of restenosis at previously dilated sites. These restenoses were treated with repeat angioplasty or stent implantation (three stents in each patient). One of these two patients developed near-occlusive restenosis of the stents and had successful bilateral lung transplantation. The other patient had a third catheterization with successful implantation of three additional stents. The third patient with recurrent symptoms died 2 years later, without further intervention. Transcutaneous catheter therapy for multiple intralobar pulmonary arterial stenoses in adults is highly successful acutely, but restenosis is common within several months. For some patients, balloon angioplasty and stent implantation may provide definitive management, while for others these procedures may serve as a bridge to lung transplantation.

In their 1993 report, Moser and Bloor [1] described an array of microvascular “pulmonary hypertensive” lesions in patients with operable chronic thromboembolic disease. Although it was concluded that these findings in any one patient did not “preclude a positive haemodynamic and clinical result”, these early observations became the foundation of our current understanding of the evolution of pulmonary hypertension and right heart failure, following the establishment of proximal vessel, occlusive organised thromboembolic disease [2, 3]. Despite the significance and role of the microcirculation in chronic thromboembolic pulmonary hypertension (CTEPH), our understanding of the histopathology remains rather rudimentary [4] and previously confined to descriptions of the precapillary pulmonary …

Patients with pulmonary hypertension due to chronic thromboembolic disease benefit from pulmonary thromboendarterectomy. A subset of these patients present with concomitant coronary or valvular disease.From July 1990 to July 2000, 90 patients (68 males, 22 females, mean age 68 years) with pulmonary vascular resistance (PVR) ranging from 297 to 2261 dynes x sec x cm(-5) underwent pulmonary thromboendarterectomy in conjunction with coronary bypass grafting (59 patients), coronary artery bypass grafting/foramen ovale closure (24 patients), tricuspid annuloplasty (3 patients), mitral valve repair (2 patients), and aortic valve replacement (2 patients). The perioperative and hemodynamic outcomes of these patients were compared with the cohort of 1,100 isolated pulmonary thromboendarterectomies performed at our institution during this time.Overall perioperative survival (93.3%; 84 of 90 patients) and mean diminution in PVR (521 dynes x sec x cm(-5)) for patients undergoing combined operations were similar to those undergoing pulmonary thromboendarterectomy alone (94.2% survival; 1034 of 1100 patients; 547 dynes x sec x cm(-5) mean PVR reduction). Although patients undergoing combined operations were older (mean age 68 vs 50 years, p0.0001), had longer hospital stays (median 14 vs 9 days), and had worse left ventricular function (mean preoperative cardiac output 3.1 vs 4.4, p0.0001), there was no difference in cross-clamp time, resolution of tricuspid regurgitation, or postoperative systolic function between these two groups.Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension may be performed safely in conjunction with other cardiac operations. Older patients evaluated for pulmonary thromboendarterectomy should be screened for concomitant coronary and valvular disease.

Obstruction of major pulmonary vessels with organized thromboemboli is a rare sequelae of acute pulmonary embolic disease. Depending on the extent and duration of vascular occlusion, patients experiencing this unusual disorder may develop significant pulmonary hypertension and cor pulmonale. If left untreated, the ultimate clinical outcome is right heart failure and death. Over the past several decades, the description of this clinical entity has evolved from an autopsy curiosity to a recognized cause of chronic pulmonary hypertension. Also, during this same time period, surgical capabilities have greatly advanced, providing these patients a potentially life-saving remedy for this debilitating form of pulmonary vascular disease. This article provides a historical perspective for our current understanding of major vessel chronic thromboembolic pulmonary hypertension as a distinct clinical disorder. It also chronicles the developments in surgical techniques that have made thromboendarterectomy of the pulmonary arterial bed a reality.

Pulmonary thromboendarterectomy (PTE) surgery is an effective treatment for the majority of patients with chronic thromboembolic pulmonary hypertension (CTEPH), with an acceptable mortality rate. The immediate outcome after PTE has repeatedly shown a dramatic decline in pulmonary vascular resistance, echocardiographic evidence of reduced right heart pressure, and increased perfusion on lung scan. Prospective long-term follow-up studies (1 to 4 years post-PTE) have found most patients to be in New York Heart Association class I or II, with significantly improved quality of life and ability to walk, climb stairs, return to work, and perform household tasks. Disease-related symptoms and hospitalizations and/or emergency room visits have also been significantly reduced. These findings indicate an improved functional status and longer life expectancy can be achieved after PTE.

Patients with sickle cell disease have been reported to have an increased risk of thromboembolism and pulmonary hypertension. Some of these patients may benefit from pulmonary thromboendarterectomy (PTE), a procedure that requires profound hypothermia, cardiopulmonary bypass, and periods of circulatory arrest, factors that may potentially increase the risk of sickling. Two patients with sickle cell disease (sickle-thalassemia [Hb S/beta+] and Hb SS) presented to the Pulmonary Vascular Center of UCSD Medical Center with significant shortness of breath and limitation of daily activities. Both of these patients were found to have surgically accessible chronic thromboembolic disease with pulmonary hypertension. PTE was performed in both patients using exchange transfusion, with avoidance of anemia, hypoxia, and acidosis. A successful outcome with resolution of pulmonary hypertension was achieved in both cases. To our knowledge this is the first report of patients with sickle cell disease who successfully underwent PTE for chronic thromboembolic pulmonary hypertension.

Background Although studies have found diminished aortic root motion in left ventricular systolic dysfunction, few data exist on aortic root excursion in isolated right ventricular dysfunction due to chronic thromboembolic pulmonary hypertension (CTEPH). Objective We conducted this study to evaluate aortic root excursion in CTEPH. Methods We studied 20 consecutive patients with CTEPH, normal left ventricular ejection fraction and pulmonary capillary wedge pressures, and 10 normal control subjects. Anterior excursion of the aortic root was measured using M-mode echocardiography as the difference between the maximal and minimal anterior distance of the posterior wall of the aortic root at the level of the aortic valve. Results Mean aortic excursion for CTEPH patients was approximately half that of normal controls (0.66 ± 0.25 cm vs. 1.16 ± 0.15 cm, P

PURPOSE : An increased occurrence of thrombotic events has been described in patients exhibiting a lupus anticoagulant (LA). In patients with chronic, major vessel thromboembolic pulmonary hypertension, not only has there been a relatively high frequency of the LA, but also an unexpected association with heparin-related thrombocytopenia. This retrospective report emphasizes the frequency of this association. PATIENTS AND METHODS : We retrospectively reviewed the medical records of 216 patients admitted to the University of California, San Diego, Medical Center who were being considered for surgical correction of their chronic thromboembolic pulmonary hypertension. For each patient, the following information was sought : presence of an LA, variation in platelet numbers during the preoperative evaluation, and determination of whether an observed thrombocytopenia was related to heparin use. RESULTS : An LA was found in 23 of the 216 patients (10.6%). Of the remaining patients, sufficient platelet data for comparison were available for 68 patients. These 68 patients constituted the control group. Within the LA group, platelet counts during the preoperative evaluation declined to 51.6% ± 16.7% of baseline counts, a highly significant difference (P