Chronic Pulmonary Thromboembolic Disease Research Articles

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference betweenSDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. Patients who had CTEPH (n = 80) or CTEPD without PH (n= 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

(957) - Comparison of CT Scoring in Chronic Thromboembolic Pulmonary Disease (CTED) versus Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

(957) - Comparison of CT Scoring in Chronic Thromboembolic Pulmonary Disease (CTED) versus Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Post-Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline.

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation-perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled.Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3±16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2±11.8mm Hg, postexercise 64.3±24.9mm Hg, p-value<.001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5±10.0% to 37.8±7.0%, p-value<.001; RV global longitudinal strain: -17.1±4.2% to -17.7±3.3%, p-value<.001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.

Multimodality imaging of acute and chronic pulmonary thromboembolic disease.

Pulmonary embolism (PE) is a pathological entity characterised by venous thromboembolism in the pulmonary arteries. It is a common entity in daily clinical practice and is the third most common cause of cardiovascular death. Correct diagnostic work-up is pivotal to ensure timely institution of appropriate therapy. This requires recognition of the characteristic imaging findings and awareness of the role and peculiarities of the different imaging techniques involved in the diagnostic and therapeutic process. This review aims to showcase the most commonly encountered imaging findings associated with pulmonary thromboembolism for each imaging modality, outline their advantages and disadvantages, and define the specific role of these techniques in the clinical setting. The latest innovations concerning the diagnostic work-up of PE will be also briefly discussed, yielding a perspective on the future developments and challenges that the radiologist will have to face in the coming years.

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

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

Pulmonary Embolism (PE) to Chronic Thromboembolic Pulmonary Disease (CTEPD): Findings from a Survey of UK Physicians.

Chronic thromboembolic pulmonary disease (CTEPD) is a complication of pulmonary embolism (PE). We conducted an online survey of UK PE-treating physicians to understand practices in the follow-up of PE and awareness of CTEPD. The physicians surveyed (N = 175) included 50 each from cardiology, respiratory and internal medicine, plus 25 haematologists. Most (89%) participants had local guidelines for PE management, and 65% reported a PE follow-up clinic, of which 69% were joint clinics. Almost half (47%) had a protocol for the investigation of CTEPD. According to participants, 129 (74%) routinely consider a diagnosis of CTEPD and 97 (55%) routinely investigate for CTEPD, with 76% of those 97 participants investigating in patients who are symptomatic at 3 months and 22% investigating in all patients. This survey demonstrated variability in the follow-up of PE and the awareness of CTEPD and its investigation. The findings support the conduct of a national audit to understand the barriers to the timely detection of CTEPD.

Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2

Introduction: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. Methods: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. Results: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82–36.32], p = 0.006). Conclusion: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.

Does pulmonary endarterectomy improve the clinical conditions of patients with chronic thromboembolic pulmonary disease without pulmonary hypertension?

To verify whether the new hemodynamic definition of PH has any implication in treatment of CTEPD patients without PH, we retrospectively analysed the clinical and functional changes determined by pulmonary endarterectomy (PEA) in 63 CTEPD patients without PH who underwent surgery at our center, comparing those in whom the hemodynamic diagnosis of PH met recent guideline recommendations versus those in whom the diagnosis only met previous hemodynamic thresholds.The results show that the vast majority of CTEPD patients without PH operated at our center would now be defined as CTEPH patients. PEA did not result in any improvement in exercise capacity nor in right ventricular function or lung function test in patients with mPAP ≤ 20 mmHg and PVR ≤ 2 WU; on the contrary, hemodynamic parameters, exercise capacity, right ventricular function and lung function significantly improved in patients with mPAP between 21 and 24 mmHg.

Assessing long-term symptoms in patients with post-pulmonary embolism syndrome using patientreported outcome measures

People who survive an episode of pulmonary embolism have an increased risk of developing chronic complications despite curative anticoagulant treatment. The association of dyspnoea, low functional capacity, right heart failure, chronic thromboembolic pulmonary hypertension, or chronic thromboembolic pulmonary disease is part of the notion of post-pulmonary embolic syndrome (PPES). The symptoms can be limiting, substantially affecting the quality of life. To improve the overall health outcomes of patients with acute pulmonary embolism, adequate measures to diagnose it and strategies to prevent long-term outcomes of pulmonary embolism are essential.The objective of this study is to provide a definition of PPES and review the most recommended patient-reported outcome measures (PROMs) for assessing the functionality of these patients.We searched PubMed for papers from the last 5 years that contain the terms: postpulmonary embolism syndrome; symptoms; PROMs; score; quality of life; dyspnea. Repetitive publications were excluded. The data from the publications have been summarized in this descriptive overview.

Chronic Thromboembolic Pulmonary Hypertension: A Review of the Multifaceted Pathobiology.

Chronic thromboembolic pulmonary disease results from the incomplete resolution of thrombi, leading to fibrotic obstructions. These vascular obstructions and additional microvasculopathy may lead to chronic thromboembolic pulmonary hypertension (CTEPH) with increased pulmonary arterial pressure and pulmonary vascular resistance, which, if left untreated, can lead to right heart failure and death. The pathobiology of CTEPH has been challenging to unravel due to its rarity, possible interference of results with anticoagulation, difficulty in selecting the most relevant study time point in relation to presentation with acute pulmonary embolism (PE), and lack of animal models. In this article, we review the most relevant multifaceted cross-talking pathogenic mechanisms and advances in understanding the pathobiology in CTEPH, as well as its challenges and future direction. There appears to be a genetic background affecting the relevant pathological pathways. This includes genetic associations with dysfibrinogenemia resulting in fibrinolysis resistance, defective angiogenesis affecting thrombus resolution, and inflammatory mediators driving chronic inflammation in CTEPH. However, these are not necessarily specific to CTEPH and some of the pathways are also described in acute PE or deep vein thrombosis. In addition, there is a complex interplay between angiogenic and inflammatory mediators driving thrombus non-resolution, endothelial dysfunction, and vascular remodeling. Furthermore, there are data to suggest that infection, the microbiome, circulating microparticles, and the plasma metabolome are contributing to the pathobiology of CTEPH.

Clinical-radiological-pathological correlation in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and potentially life-threatening complication of acute pulmonary embolism. It is characterised by persistent fibro-thrombotic pulmonary vascular obstructions and elevated pulmonary artery pressure leading to right heart failure. The diagnosis is based on two steps, as follows: 1) suspicion based on symptoms, echocardiography and ventilation/perfusion scan and 2) confirmation with right heart catheterisation, computed tomography pulmonary angiography and, in most cases, digital subtraction angiography. The management of CTEPH requires a multimodal approach, involving medical therapy, interventional procedures and surgical intervention. This clinical-radiological-pathological correlation paper illustrates the diagnostic and therapeutic management of two patients. The first had chronic thromboembolic pulmonary disease without pulmonary hypertension at rest but with significant physical limitation and was successfully treated with pulmonary endarterectomy. The second patient had CTEPH associated with splenectomy and was considered unsuitable for surgery because of exclusive subsegmental lesions combined with severe pulmonary hypertension. The patient benefited from multimodal treatment involving medical therapy followed by multiple sessions of balloon pulmonary angioplasty. Both patients had normalised functional capacity and pulmonary haemodynamics 3-6 months after the interventional treatment. These two examples show that chronic thromboembolic pulmonary diseases are curable if diagnosed promptly and referred to CTEPH centres for specialist treatment.

Chronic thromboembolic pulmonary disease: Association with exercise-induced pulmonary hypertension and right ventricle adaptation over time

Background and AimChronic thromboembolic pulmonary disease (CTEPD) is a progressive condition caused by fibrotic thrombi and vascular remodeling in the pulmonary circulation despite prolonged anticoagulation. We evaluated clinical factors associated with CTEPD, as well as its impact on functional capacity, pulmonary haemodynamics at rest and after exercise, and right ventricle (RV) morphology and function. MethodsWe compared 33 consecutive patients with a history of acute pulmonary embolism and either normal pulmonary vascular imaging (negative Q-scan, group 1, n = 16) or persistent defects on lung perfusion scan (positive Q-scan) despite oral anticoagulation at 4 months (group 2, n = 17). Investigations included thrombotic load, the Pulmonary Embolism Severity Index (PESI) score, functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and at 24 months. ResultsCompared with group 1, group 2 featured a higher PESI score (p = 0.02) and a higher thrombotic load (p = 0.004) at hospital admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p < 0.001) and ESE (p < 0.001). At 24 months group 2 showed higher NT-proBNP (p < 0.001), WHO-FC (p < 0.001), systolic (p<0.001) and diastolic (p = 0.037) RV dysfunction and worse RV-arterial coupling (p < 0.001) despite maintaining a low or intermediate echocardiographic probability of PH. ConclusionsThis is the first "proof of concept" study showing that patients with a positive Q-scan frequently develop Ex-PH and RV functional deterioration as well as reduced functional capacity, generating the hypothesis that Ex-PH could help detect the progression to CTEPD.

Hughes-Stovin syndrome-An important differential diagnosis in patients with suspected chronic thromboembolic pulmonary hypertension : Acase report.

Hughes-Stovin syndrome (HSS) is arare vasculitis of unknown etiology. The disease is characterized by pronounced inflammation and damage to the vessel walls, with subsequent widespread vascular thrombosis and the formation of pulmonary artery aneurysms that can lead to fatal hemoptysis. This disorder can be mistaken for other conditions, such as chronic thromboembolic pulmonary disease (CTEPD) without or with pulmonary hypertension at rest (CTEPH).We report the case of a20-year-old female with HSS, which was misdiagnosed as CTEPH and subsequently treated with anticoagulants, which led to severe hemoptysis and eventually death of the patient. This case highlights the challenges of diagnosing HSS at early stages of the disease.HSS should be considered in young patients with signs of large vessel vasculitis in combination with thrombotic occlusions of pulmonary arteries, with or without aneurysms of the pulmonary arteries, and particularly, if there are no risk factors for thromboembolic disease.

Value of exercise right heart catheterization for differential diagnosis of dyspnoea in chronic thromboembolic pulmonary disease

Abstract Background and Purpose Chronic thromboembolic disease (CTED) refers to chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but functional limitation attributable to incipient vasculopathy. Our aim is to evaluate the hemodynamic response to exercise in patients with suspected CTED without relevant resting PH. Methods We prospectively included symptomatic patients with persistent pulmonary thrombosis despite optimal anticoagulant therapy for a minimum of 3 months. Patients with left heart disease and abnormal lung function tests were excluded. Patients included had mean pulmonary arterial pressure (mPAP ) ≤25 mmHg, pulmonary vascular resistance (PVR) &amp;lt; 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Exercise right heart catheterization (RHC) was performed via supine cycle ergometry. Exercise precapillary PH was defined as mPAP/CO slope &amp;gt;3 mmHg/l/min and PAWP/CO slope &amp;lt;2 mmHg/l/min. We made a subanalysis of those patients who fulfilled the new definition of resting PH (mPAP&amp;gt;20mmHg &amp; PVR &amp;gt; 2 WU) Results We studied 39 patients (mean age 52.7 ± 15.7 years, 36 % women): 12 of them met new resting PH criteria (mPAP &amp;gt; 20 mmHg &amp; RVP &amp;gt; 2 WU) , and 27 had normal resting hemodynamic. Baseline characteristics are summarized in Table 1 and did not reveal differences between groups except for haemodynamic parameters. From the entire cohort, 20 patients developed exercise PH: 14 (36%) with a precapillary pattern, and in 6 (15.4%) patients, the abnormal response was described as an abnormal PAWP/CO relationship during exercise. Exercise precapillary PH was documented in 67% of patients with resting PH according to the new PH criteria versus 37% of those without resting PH (Figure 1). Conclusion The functional limitation appears to be attributable to exercise precapillary PH in 36 % of patients with CTED suspicion and absence of significant resting PH. Exercise RHC is a valuable tool for diagnosing CTED and detecting other causes of dyspnoea, such as diastolic dysfunction. New resting PH haemodynamic criteria predict a higher percentage of abnormal exercise response, but one-third of patients develop exPH despite normal haemodynamic at rest.

Usefulness of cardiopulmonary exercise test to detect exercise pulmonary hypertension in the post pulmonary embolim follow-up

Abstract Functional impairment is largely reported after symptomatic pulmonary embolism (PE). Chronic thromboembolic pulmonary disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with incipient vasculopathy responsible for exercise limitation. Exercise haemodynamic studies have emerged to detect an abnormal response suggesting an established vasculopathy or an abnormal left ventricular filling pressure. We hypothesized that exercise intolerance due to an abnormal haemodynamic response during exercise might be unmasked by the parameters exhibited at the cardiopulmonary exercise test (CPET) in diagnostic workup after PE in symptomatic patients. Our aim was to correlate the values reached in the CPET pattern with haemodynamic response during exercise right heart catheterization (RHC) in patients with CTED suspicion. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 3 months after a PE with normal lung function tests. Left heart disease and significant PH were ruled out with RHC (inclusion criteria implied mean pulmonary arterial pressure (mPAP) &amp;lt; 25 mmHg and pulmonary vascular resistance (PVR) &amp;lt; 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg). Exercise RHC was performed sequentially 24 hours after CPET. The exercise protocol was the same for both tests. Pulmonary pressure and cardiac output (CO) were collected at each exercise leel. Exercise PH (ex-PH) was considered when mPAP/CO slope &amp;gt;3 mmHg·L−1·min−1. We made a subanalysis according to the new PH criteria (mPAP &amp;gt;20mmHg &amp; PVR &amp;gt; 2 WU at rest). Results 39 patients (median age 52.7 ± 15.7 years, 36% females) were included. 21 (53.8%) showed abnormal haemodynamic behaviour, 6(15.4%) of them due to abnormal PWAP/CO slope. Baseline characteristics are summarized in Table 1. Patients with abnormal exercise response showed worse ventilatory efficiency at exercise: 1) reduced partial end-tidal of carbon dioxide (PetCO2) at the anaerobic threshold (AT) (32.0 Vs 36.4, p=0.001), 2) a steeper VE/CO2 slope (35.6 Vs 30.9, p=0.009) and 3) a higher ventilatory equivalent for CO2 at the AT (35.5 Vs 31.6, p=0.004) compared to the group with normal hemodynamic behaviour. Oxygen consumption at the AT and peak oxygen consumption were slightly decreased without statistically significant differences between groups.Of the global cohort, 11 patients reached new resting PH criteria, and 92% of them showed ex-PH. Ventilatory efficiency showed differences in the subgroup with normal resting hemodynamic values, especially lower PetCO2 at the AT (31.8 Vs 35.0, p=0.008) (Figure 2). Conclusion In the context of persistent dyspnoea after PE, ventilatory inefficiency is a sign of exercise pulmonary hypertension, and CPET could identify patients with abnormal exercise response despite normal hemodynamic values at rest.

TAPSE/sPAP at peak exercise as a surrogate of RV-PA uncoupling can predict exercise-induced pulmonary hypertension in symptomatic patients with chronic thromboembolic pulmonary disease

Abstract Background and aim Chronic thromboembolic disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with exercise limitation caused by established vasculopathy. Symptoms after an acute pulmonary embolism (PE) with persistent lung perfusion defects need a complete diagnostic approach. Exercise echocardiography (ex-echo), with surrogate parameters of ventricular-arterial (VA) coupling could be of interest to non-invasively assess a pathological hemodynamic response. The aim of this study is to analyze the role of ex-echo and non-invasive assessment of VA coupling by echocardiography in predicting an abnormal hemodynamic response in symptomatic patients with chronic thrombotic pulmonary vascular occlusion. Methods Symptomatic patients with confirmed perfusion defects in lung V/Q scintigraphy despite optimal anticoagulant therapy for at least 3 months after an acute PE were selected. Relevant PH at rest was ruled-out (mPAP &amp;lt;25 mmHg, PVR &amp;lt;3 Wu, PAWP &amp;lt;15 mmHg, according to available definition at the time). Right heart catheterization with incremental exercise protocol (adapted cycle ergometer), with simultaneous transthoracic echo were performed. Parameters were collected at each exercise level. A mPAP/CO slope &amp;gt;3 mmHg·L−1·min−1 measured invasively was considered an abnormal hemodynamic response to exercise. Right VA coupling was estimated as TAPSE/sPAP ratio. A non invasive echo mPAP/CO slope was obtained from Doppler measurements. Results 31 patients (32% women, mean age 51.8 ± 14.7 y.) were included. Fourteen patients (45%) developed ex-PH. Baseline and peak exercise characteristics and parameters according to hemodynamic response are shown in Table 1. Moderate significative correlations between invasive hemodynamics and echo derived parameters at peak exercise were observed: sPAP: r=0.793 (p &amp;lt;0.001), CO r=0.532 (p 0.003), mPAP/CO slope r=0.458 (p 0.012). Peak exercise TAPSE/sPAP showed an AUC=0.85 (CI95% 0.70-1.00, fig. 1), and a cutoff point of &amp;lt;0.52 mm/mmHg, showed a S 80% / E 93% PPV 92% and NPV 81%, to predict an abnormal response. The echo derived mPAP/CO slope showed an AUC=0.78 (CI95% 0.59-0.96), and a cutoff point of &amp;gt; 2.44 mmHg·L−1·min−1 showed a S and E of 85% and 67% PPV 71 % and NPV of 83% to predict ex-PH. Abnormal septal motion at peak exercise showed a S 90%, E 78%, PPV 71% and NPV of 93% to predict ex-PH. Conclusions In our study cohort, up to 45% of symptomatic patients with persistent pulmonary thrombosis after a PE, without relevant PH at rest, developed ex-PH. New echo-derived parameters such as TAPSE/sPAP, a surrogate RV-PA coupling parameter, and echo-mPAP/CO slope, showed a good performance to predict an abnormal hemodynamic response. Ex-echo, feasible, non invasive and widely available, might represent a useful tool for the selection of patients for invasive hemodynamic workup.Peak exercise TAPSE/sPAP ROC curveTable 1

Resting RV-PA uncoupling as predictor of exercise induced pulmonary hypertension in patients with chronic thromboembolic pulmonary disease

Abstract Background and aim Chronic thromboembolic disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with exercise limitation caused by established vasculopathy. Symptoms after an acute pulmonary embolism (PE) with persistent lung perfusion defects need a complete diagnostic approach. Screening these symptomatic patients with resting echocardiography (echo) is challenging. The aim of this study is to analyze the echocardiographic predictors at rest of exercise induced PH (ex-PH) in patients with suspected CTED. Methods Symptomatic patients with confirmed perfusion defects in lung V/Q scintigraphy despite optimal anticoagulant therapy for at least 3 months after an acute PE were selected. Structural heart disease or pulmonary disease were excluded. Relevant PH at rest was ruled-out (mPAP &amp;lt;25 mmHg, PVR &amp;lt;3 Wu, PAWP &amp;lt;15 mmHg according to available definition at the time). A right heart catheterization with incremental exercise protocol (cycle ergometer), and simultaneous transthoracic echo were performed. Hemodynamic and echo parameters were collected at each exercise level. A mPAP/CO slope &amp;gt;3 mmHg·L−1·min−1 was considered an abnormal hemodynamic response to exercise. Right V-PA coupling was estimated as TAPSE/sPAP and RV free wall global longitudinal strain (RV-GLS)/sPSP ratios. Results 31 patients (32% women, mean age 51.8 ± 14.7 y) were included. Fourteen patients (45%) developed ex-PH. Baseline characteristics according to invasive hemodynamic response are shown in Table 1. Resting RV function (TAPSE and RV-GLS), but not size, was significatively impaired in the ex-PH cohort. Resting echo sPAP or TR max velocity did not achieve any difference between groups, although invasive sPAP did. Resting TAPSE/sPAP and RV-GLS/sPAP were significantly reduced in the ex-PH group. In ROC curve, resting TAPSE/sPAP showed an AUC 0.75 (CI 95% 0.56-0.95) to predict ex- PH. A cutoff point of &amp;lt;0.62 mm/mmHg at rest, showed a S 88% / E 71%, PPV 78.9 % and NPV 83.3%. Resting RV-GLS/sPAP ratio showed an AUC 0.859 (CI 95% 0.708 – 0.990) to predict ex- PH. A cutoff point of &amp;gt; - 0.67 %/mmHg, showed a S 75.0% / E 87.5%, PPV 78.2 % and NPV 82.4%. to predict ex- PH. Conclusions Exercise limitation appears to be attributable to ex-PH in up to 45% of symptomatic patients with persistent pulmonary thrombosis after a PE without relevant PH at rest. Echo derived parameters at rest, surrogates of RV-PA uncoupling, such as TAPSE/sPAP and RV-GLS/sPAP, could be of great interest to identify patients with abnormal hemodynamic response to exercise, and help in the initial non invasive diagnostic workup of these increasingly group of patients.ROC curvesTable 1Resting Echo values