Thromboembolic Pulmonary Hypertension Patients Research Articles

External validation of the InShape II study algorithm for exclusion of chronic thromboembolic pulmonary hypertension in patients with pulmonary thromboembolism

Background and aimThe most severe long-term complication of pulmonary embolism (PE) is chronic thromboembolic pulmonary hypertension (CTEPH), and its early diagnosis often requires numerous diagnostic tests. The InShape II study proposes an early screening algorithm that aims to reduce the number of echocardiographic studies. The objective of our study is to validate this algorithm in our patient cohort. Materials and methodsWe retrospectively analyzed patients admitted to Hospital Rey Juan Carlos between November 2017 and February 2020, who were diagnosed with PE based on computed tomography angiography (CTA). Patients were followed for at least one year, and clinical, laboratory, and complementary test data were collected at three months and one year. The InShape II algorithm was applied to these patients to validate its results. ResultsDuring the study period, 236 patients were diagnosed with PE, of which 137 were excluded. The algorithm was validated in 99 patients. Applying the InShape II score, 19 echocardiograms would have been performed (three of them with intermediate-high probability of CTEPH), while 80 echocardiograms would have been avoided (two of them with intermediate-high probability). This yielded a sensitivity of 60% and a specificity of 83% for the score, with an area under the curve (AUC) of 0.715 (95% CI: 0.472–0.958). ConclusionsOur results support the notion that the InShape II algorithm could be a useful tool for initial screening of CTEPH in low-incidence settings, as it would avoid unnecessary echocardiograms that do not provide additional value.

Predictors of chronic thromboembolic pulmonary hypertension in patients with submassive pulmonary embolism treated with catheter-directed thrombolysis versus anticoagulation alone: A secondary analysis of the SUNSET sPE trial

ObjectiveChronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is a morbid complication with suboptimal treatment. We aimed to evaluate the biomarker profile and functional outcomes in patients with submassive PE (sPE) treated with catheter-directed thrombolysis (CDT) compared with anticoagulation alone (ACA). We performed a secondary biomarker and survey analysis of the SUNSET sPE (standard vs ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism) randomized trial comparing standard CDT to ultrasound-assisted thrombolysis in patients with sPE. MethodsAs a part of the SUNSET sPE study, patients who did not receive an intervention were enrolled in the medical (ACA) arm. The biomarkers associated with CTEPH in the literature (ie, CCL2, CXCL10, PTX3, GDF-15, RAGE, BCA-1, TFPI) were collected and measured using a multiplex assay at diagnosis, discharge, and 3-month follow-up. Patients underwent a 6-minute walk test and answered quality-of-life questionnaires (pulmonary embolism quality of life; University of California, San Diego, shortness of breath questionnaire; 36-item short-form survey) at 3 months after diagnosis. Comparisons were made using the Student t test. Nonparametric tests were used when the distributions were not normal. Significance was set at P ≤ .05. ResultsA total of 72 patients (age, 56 ± 15 years; 40.3% women) were included in the present analysis. Of these 72 patients, 53 underwent CDT and 19 were included in the ACA arm. The baseline right ventricle/left ventricle ratios were similar between the two groups (CST, 1.8; ACA, 1.7). The survival and complication rates were similar between the two groups. At discharge, CXCL10 (768.9 ± 148.6 pg/mL vs 3032.0 ± 1201.0 pg/mL; P = .018) and PTX3 (3203.5 ± 1298.0 pg/mL vs 12,716.2 ± 6961.5 pg/mL; P = .029) were lower in the CDT group and displayed a quicker return to baseline than in the ACA group. This trend, although not significant, was also seen with the other biomarkers. At 3 months, the 6-minute walking distance and quality-of-life scores were similar between both groups. ConclusionsIn patients with sPE, the biomarkers of CTEPH were lower with CDT compared with ACA. At 3 months, both groups demonstrated similar biomarker levels, 6-minute walking distances, and quality-of-life scores.

The Outcome of Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension during the COVID-19 Pandemic.

The coronavirus 2019 (COVID-19) has affected the lives of many people worldwide. Patients with chronic underlying morbidities are vulnerable to get the severe form of the infection. The goal of this study was to evaluate the outcome of patients with pulmonary arterial hypertension during the COVID-19 pandemic in Iran. This cross-sectional study was conducted at a large tertiary center for pulmonary artery hypertension (PAH) patients. The primary end point was the prevalence of SARS-CoV-2 infection in PAH patients. The secondary end points were investigating the severity and mortality of COVID-19 infection in PAH patients during the COVID-19 pandemic. Totally 75 patients were enrolled in the study from December 2019 to October 2021 and 64% were female. The mean ± SD age was 49 ± 16 years. The prevalence of COVID-19 in PAH/chronic thromboembolic pulmonary hypertension patients was 44%. About 66.7% of patients had comorbidities, which was a prognostic factor for COVID-19 infection in PAH patients (P < 0.001). Fifty-six percent of infected patients were asymptomatic. The most reported symptoms in symptomatic patients were fever (28%) and malaise (29%). Twelve percent of patients were admitted with severe symptoms. The mortality rate in infected individuals was 3.7%. COVID-19 infection in PAH/chronic thromboembolic pulmonary hypertension patients seems to be associated with high mortality and morbidity. More scientific proof is needed to clarify different aspect of COVID-19 infection in this population.

Diagnostic efficacy of ECG-derived ventricular gradient for the detection of chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism

IntroductionApplication of the chronic thromboembolic pulmonary hypertension (CTEPH) rule out criteria (manual electrocardiogram [ECG] reading and N-terminal pro-brain natriuretic peptide [NTproBNP] test) can rule out CTEPH in pulmonary embolism (PE) patients with persistent dyspnea (InShape II algorithm). Increased pulmonary pressure may also be identified using automated ECG-derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO). MethodA predefined analysis of the InShape II study was performed. The diagnostic performance of the VG-RVPO for the detection of CTEPH and the incremental diagnostic value of the VG-RVPO as new rule-out criteria in the InShape II algorithm were evaluated. Results60 patients were included; 5 (8.3%) were ultimately diagnosed with CTEPH. The mean baseline VG-RVPO (at time of PE diagnosis) was −18.12 mV·ms for CTEPH patients and − 21.57 mV·ms for non-CTEPH patients (mean difference 3.46 mV·ms [95%CI −29.03 to 35.94]). The VG-RVPO (after 3–6 months follow-up) normalized in patients with and without CTEPH, without a clear between-group difference (mean Δ VG-RVPO of −8.68 and − 8.42 mV·ms respectively; mean difference of −0.25 mV·ms, [95%CI −12.94 to 12.44]). The overall predictive accuracy of baseline VG-RVPO, follow-up RVPO and Δ VG-RVPO for CTEPH was moderate to poor (ROC AUC 0.611, 0.514 and 0.539, respectively). Up to 76% of the required echocardiograms could have been avoided with VG-RVPO criteria replacing the InShape II rule-out criteria, however at cost of missing up to 80% of the CTEPH diagnoses. ConclusionWe could not demonstrate (additional) diagnostic value of VG-RVPO as standalone test or as on top of the InShape II algorithm.

Efficacy of intermittent inhaled iloprost in inoperable chronic thromboembolic pulmonary hypertension

PH (pulmonary hypertension) targeted therapy may play an essential role in chronic thromboembolic pulmonary hypertension (CTEPH) patients considered inoperable. Given the limited number of PH-targeted drugs approved for CTEPH, reliable long-term data are necessary on the effects of PH-targeted drugs in patients with inoperable CTEPH. We aimed to evaluate the efficacy and safety of intermittent inhaled iloprost in inoperable CTEPH. Methods. The open randomized controlled trial included 22 inoperable CTEPH patients (aged (Me (25%; 75%)) 48,3 (38,4; 59,5) years; 63.6% females; 9.1% with WHO functional class (FC) IV, 72.7% with WHO-FC III, 18.2% with WHO-FC II; 6-minute walking test (6-MWT) distance of 348 (145; 443) m; mean pulmonary artery pressure (mPAP) of 41.8 (29.3; 52.8) mmHg; tricuspid annular plane systolic excursion (TAPSE) of 16.3 (14.5; 18.2) mm; plasma NT-proBNP of 853.8 (562.2; 1124.2) pg/mL). The patients were enrolled 3 – 6 months after acute pulmonary embolism and were randomized 1:1 to receive either standard therapy with vitamin K antagonists and, if indicated, oxygen and diuretics or inhaled iloprost 5.0 µg / inhalation 4 times a day for 2 weeks every 3 months for 2 years in addition to the standard of care. Efficacy endpoints included changes from baseline in 6-MWT, WHO-FC, echo-parameters, inflammatory markers, time to clinical worsening, and all-cause mortality. Results. At baseline (prior to therapy), there were no significant differences between iloprost and control groups. Levels of C-reactive protein and the interleukin (IL)-1b, IL-6, IL-8, γ-IF, and TNF-α cytokines were increased. At month 24, a mean 6-MWT distance increased by 215 m (p &lt; 0.001) in the patients receiving inhaled iloprost and by 137 m in the control patients (p &lt; 0.01). The control-adjusted difference was +78 m (p = 0.03). WHO-FC improved by two classes in 63.6% in iloprost group vs 0% in the control group (p = 0.028), by one class in 36.4% vs 30% (p = 0.091), and remained the same in 0% vs 70 % (p = 0.018), respectively. Inhaled iloprost delayed the time to clinical worsening (p = 0.0064). Improvements were noted in control-adjusted changes in ePASP (–18.6 mmHg; p = 0.0065), TAPSE (+2.4 mm; p = 0.028), and plasma NT-proBNP (–256.9 pg/mL; p &lt; 0.01). The levels of inflammation decreased significantly in the iloprost group, while remained unchanged in the control group. Combination therapy with inhaled iloprost was tolerated well. One patient died in the control group (p = 0.093). Conclusion. Long-term intermittent inhaled iloprost for patients with inoperable CTEPH may improve their clinical status, hemodynamics, and anti-inflammatory status.

Abstract 12168: Long-Term Effects of Pulmonary Endarterectomy on Pulmonary Hemodynamics and RV Function in Chronic Thromboembolic Pulmonary Hypertension

Background: Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to improvement in right ventricular (RV) function in the majority of chronic thromboembolic pulmonary hypertension (CTEPH) patients. However, little is known about the long-term effects of PEA on RV function. We aimed to describe long-term changes in RV function in PEA treated CTEPH-patients. Methods: In this prospective study we included patients diagnosed with CTEPH who underwent PEA. Structured follow-up measurements were performed using right heart catheterization (RHC) and cardiac magnetic resonance (CMR) imaging before PEA and 6 and 18 months after treatment. Single beat pressure-volume loop analysis was used to determine load-independent RV contractility (Ees) and RV afterload (Ea). RV volume, mass and function were derived from CMR. Results: The study protocol was completed in 25 CTEPH-patients. PEA led to a significant decline in mean pulmonary arterial pressure (mPAP 45±11 to 24±9 mmHg; p&lt;0.0001), pulmonary vascular resistance (PVR 561 [427-711] to 132 [112-194] dynes/s/cm 5 ; p&lt;0.0001) and RV afterload (Ea 0.6 [0.49-0.81] to 0.2 [0.2-0.3] mmHg/ml; p&lt;0.0001) 6 months after treatment. In addition, RV dimensions improved 6 months after PEA as demonstrated by a decrease in indexed RV end-diastolic volume (RVEDVi 91±28 to 71±13 ml/m 2 ; p=0.0009), indexed RV mass (43±15 to 27±11 g/m 2 ; p &lt;0.0001) and increase in RV ejection fraction (RVEF 41±14 to 52±9%; p=0.0003) and Ees (0.7 [0.5-1.1] to 0.3 [0.2-0.4] mmHg/ml; p&lt;0.0001). No further changes were seen in pulmonary hemodynamics and RV dimensions between 6 and 18 months after PEA. Conclusion: Restoration in pulmonary hemodynamics and RV dimensions occurs within 6 months after PEA. No further improvements are observed between 6 and 18 months after PEA.

Chronic thromboembolic pulmonary hypertension in patients with antiphospholipid syndrome: Risk factors and management

Antiphospholipid syndrome (APS) may cause chronic thromboembolic pulmonary hypertension (CTEPH). Current knowledge regarding prevalence and risk factors for CTEPH among APS patients is limited. We sought to determine clinical features and biomarkers that could identify APS subjects suffering from CTEPH, and describe the prevalence, course and treatment outcomes of patients with APS-CTEPH. 504 APS patients were treated in our center during 2008 to 2019. We studied clinical and laboratory features of 69 APS patients, comparing 19 patients diagnosed with CTEPH (APS-CTEPH) and treated accordingly, with 50 consecutive age and gender matched patients with no evidence of pulmonary hypertension (APS-No-CTEPH). CTEPH prevalence was 3.8% in our APS cohort and was linked with the following parameters: primary APS (p < 0.05); prior pulmonary embolism (p < 0.001); recurrent venous thromboembolism (VTE) (p < 0.001); lower platelet counts (p < 0.001); triple anti-phospholipid antibodies positivity (p < 0.001), higher titers of anti-cardiolipin IgG (p < 0.001), anti-B2GPI IgG (p < 0.001), and high Russell viper venom time ratio (RVVT-ratio) (p < 0.05). Additionally, history of catastrophic APS was more prevalent in APS-CTEPH vs APS-No-CTEPH (p < 0.05). Of APS-CTEPH patients, 15/19 underwent pulmonary endarterectomy (PEA): In 12/15 the procedure was elective and resulted in good perioperative and long-term outcomes, while only 1 of 3 patients that underwent urgent PEA survived. CTEPH is relatively common in APS. Primary APS, prior PE, recurrent VTE, thrombocytopenia and specific anti-phospholipid antibodies predict CTEPH in APS. Active assessment for CTEPH in APS patients should be considered, as PEA was found to be effective and relatively safe, especially if electively performed.

Circulating proteomic biomarkers related to the development of chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH), known as a complication of acute pulmonary embolism (PE), can be attributed to both persistent organized thrombi and small-vessel disease. It has been reported that patients with acute PE are more likely to develop CTEPH or have a worse prognosis in follow-up if they have pulmonary hypertension (PH) or right ventricular dysfunction in their acute phase; in acute PE, increased pulmonary arterial pressure can be induced by a combination of mechanical obstruction and pulmonary vasoconstriction. However, it remains unknown whether contributors to the increase pulmonary arterial pressure in acute phase would persistently influence the pulmonary vasculature, which could further lead to the development and progression of CTEPH. Purpose To investigate underlying contributors related to pulmonary hypertension in acute PE that would persistently influence the pulmonary vasculature in the development of CTEPH, and to explore potential biomarkers predictive of CTEPH in acute PE. Methods Plasma from patients with acute PE were collected and classified into Group 1 (with PH) and Group 2 (without PH) according to the presence of PH, which was defined by echocardiographic estimated “high probability” of PH as recommended in the 2015 ESC/ERS Guidelines for the diagnosis and treatment of PH. In addition, plasma from patients with acute PE who had not developed PH both in their acute and follow-up phase but had persistent thrombi (Group 3) were also studied and compared to that of CTEPH patients (Group 4). Differential expression proteins (DEPs) between 4 groups were identified in terms of data-independent acquisition-based quantitative proteomic analysis. Results Twenty-two DEPs were identified between Group1 and Group 2, and 105 DEPs were identified between Group 3 and Group 4. Among two groups of DEPs, 8 proteins were in common: antithrombin-III, osteopontin, properdin, desmoplakin, C1QA (complement C1q subcomponent subunit A), LDHA (L-lactate dehydrogenase A chain), IGKV1D-33 (immunoglobulin kappa variable 1D-33) and PEPD (Xaa-Pro dipeptidase). The level of LDHA, antithrombin-III, osteopontin and properdin were decreased both in acute PE patients with PH and CTEPH patients, while the level of desmoplakin, C1QA and IGKV1D-33 were increased in the above two groups. Regarding PEPD, its level was lower in acute patients with PH but was higher in CTEPH. Based on underlying pathogenic mechanism and the percentage of missing value, osteopontin, properdin, desmoplakin, C1QA, LDHA and PEPD were further validated as potential biomarkers predictive of CTEPH in acute PE. Conclusions Contributors to the increase pulmonary arterial pressure in acute PE can be further involved in the development of CTEPH, and these proteins can be potential biomarkers to help guide the management and follow-up strategy in acute PE. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS; No. 2017-12M-1-009); National Key Research and Development Program of China (No: 2016YFC1304400) Differential expression proteinsRelative intensity of proteins

Chronic thromboembolic pulmonary hypertension in patients with persistent chest symptoms after acute pulmonary embolism.

This study aimed to analyze the role of chronic thromboembolic pulmonary hypertension (CTEPH) in patients with persistent chest symptoms after acute PE. Patients aged between 18 and 80 years who were followed up for acute PE were screened for chest symptoms which persisted after the anticoagulation treatment. Patients suffering other types of pulmonary hypertension (PH) or metastatic malignancies were excluded in this study. Demographic and functional data of patients included this study were collected. The patients underwent transthoracic echocardiography and ventilation/perfusion (VQ) scans. Also, invasive hemodynamic studies were done to patients with intermediate/high probability of VQ scans. Of the 140 patients screen for this study, 29 patients (Female/Male=16/13) with mean age of 56.1±11.2 years and follow-up time of 35.1±17.7 months met the inclusion criteria. The mean systolic pulmonary artery blood pressure (sPAP) on transthoracic echocardiography was 28.9±4.9 mm Hg (range=20-40 mm Hg). Furthermore, intermediate or high probability of VQ scans was detected in 2 patients, who were subsequently diagnosed with CTEPH (6.9%) via right heart catheterization. CTEPH was diagnosed at a low rate in patients with persistent chest symptoms after the anticoagulation treatment for PE. CTEPH is still an elusive entity, which requires a multidisciplinary and invasive approach.

P4670Long-term changes of exercise haemodynamics and physical capacity in chronic thromboembolic pulmonary hypertension after pulmonary thromboendarterectomy

Abstract Background A substantial number of chronic thromboembolic pulmonary hypertension (CTEPH) patients experience dyspnoea on exertion and limited exercise capacity despite surgically successful pulmonary endarterectomy (PEA). Purpose We sought to prospectively evaluate resting and peak exercise haemodynamics before, 3 and 12 months after PEA in consecutive CTEPH patients and correlate it to physical functional capacity. Methods Twenty CTEPH patients who underwent PEA treatment were examined between December 2014 and January 2017. The patients were examined pre-operatively and 3 and 12 months post-operatively with right heart catheterisation at rest and during a maximal symptom-limited, semi-supine cardiopulmonary exercise test. Finally, the data were compared with 15 healthy controls who had previously undergone the same protocol. Results Twelve months after PEA, 75% of patients with severely increased pre-PEA mean pulmonary arterial pressure (mPAP) at rest had normal or mildly increased mPAP. However, mPAP reduction was less pronounced during exercise where only 45% had normal or mildly increased mPAP at 12 months. Cardiac output (CO) reserve (CO increase from rest to peak exercise) was increased (5.7±2.9 L/min) 12 months after PEA compared with pre-PEA (2.5±1.8 L/min), p&lt;0.0001. However, 12 months after PEA, the CO reserve was only 49% of that of healthy controls, p&lt;0.0001. Changes in cardiac output (ΔCO), calculated as the difference between CO before PEA and 12 months later, were significantly correlated with six-minute-walk-test and peak oxygen uptake (VO2), both at rest and peak exercise. Figure 1 Conclusion Invasive exercise haemodynamic examination in CTEPH patients demonstrates that after otherwise successful PEA surgery, more than 50% of patients have a significant increase in exercise mPAP, and the CO reserve remains compromised 12 months after PEA. Improvement in physical capacity is correlated with ΔCO. Acknowledgement/Funding Danish Heart Foundation, Aarhus University, Arvid Nilssons Fond, Eva &amp; Henry Frænkels Mindefond, and Snedkermester Sophus Hustru Astrid Jacobsens Fond

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

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

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients with diagnosis of pulmonary embolism for the first time in real world.

The incidence and risk factors of chronic thromboembolic pulmonary hypertension (CTEPH) in patients with acute pulmonary embolism (PE) have been well reported. However, in real world, patients diagnosed with PE for the first time were usually composed of acute PE, sub-acute PE, and chronic PE, and the cumulative incidence and risk factors of CTEPH in this cohort were still unknown. A prospective, long-term, follow-up study was conducted to assess the incidence of symptomatic CTEPH in consecutive patients with PE diagnosed for the first time. Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and, if the findings indicated pulmonary hypertension, ventilation-perfusion lung scanning and right heart catheterization. CTEPH was confirmed if perfusion defects were present, mean pulmonary artery pressure (mPAP) ≥25mmHg and pulmonary artery wedge pressure (PAWP) ≤15mmHg. The cumulative incidence of CTEPH in patients with PE diagnosed for the first time was 11.2% at 3 months, 12.7% at 1 year, 13.4% at 2 years, and 14.5% at 3 years. The following factors increased the risk of CTEPH: time from symptoms to treatment of PE ≥1month (odds ratio (OR), 14.77), intermediate (OR, 37.63) to high risk PE (OR, 39.81), segmental and sub-segmental branch location of embolism (OR, 8.30) and PE-related primary risk factors (OR, 5.01). 9.4% of CTEPH patients developed from acute PE, and 90.6% from sub-acute and chronic PE. In real world, CTEPH is a relatively common and serious complication in PE patients diagnosed for the first time. Early diagnosis and treatment of PE will decrease the incidence of CTEPH in these unspecified patients.

The value of speckle-tracking echocardiography in identifying right heart dysfunction in patients with chronic thromboembolic pulmonary hypertension

Right ventricular (RV) function is a significantly important factor in the determination of the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) patients. Speckle-tracking echocardiography (STE) is an angle-independent new technique for quantifying myocardial deformation that is capable of providing data on multiple parameters including longitudinal and transverse information of the myocardium. In the present study, we aimed to study the advantages of STE-derived parameters in identifying RV dysfunction in CTEPH patients. Sixty CTEPH patients (mean age: 55 years ± 13 years; 25 males) and 30 normal controls (mean age: 54 years ± 14 years; 14 males) were enrolled in this study. RV free wall (RVFW) systolic peak longitudinal strain (LS) including the basal, mid-, and apical-segments and the basal longitudinal and transverse displacement (basal-DL and basal-DT) were measured by STE. Global LS (GLS) of the RV was calculated by averaging the LS value of the 3 segments of RVFW. Clinical data of CTEPH patients were collected. CTEPH patients were divided into 2 subgroups according to the World Health Organization function classification. Clinical right heart failure (RHF) was defined as the presence of symptoms of heart failure and signs of systemic circulation congestion during hospitalization. The apical segment LS of the RVFW was lower than that in the basal and mid-segments in the control group (P < 0.001), but no significant difference was found among the 3 segments of LS in the CTEPH group (P = 0.263). When we used the cutoff value recommended by the American Society of Echocardiography guidelines to identify abnormal RV function, 30 CTEPH patients (50%) by tricuspid annular plane systolic excursion (TAPSE), 42 patients (70%) by fractional area change (FAC), 20 patients (33.33%) by RV index of myocardial performance (RVIMP), and 46 patients (77%) patients by GLS were determined to have abnormal RV function, respectively. Among multiple RV function indicators, TAPSE, FAC, GLS, basal-DL, and N-terminal pronatriuretic B-type natriuretic peptide showed significant differences between CTEPH patients with mild (WHO II) and severe symptoms (WHO III/IV) (all P < 0.001), while RVIMP and basal-DT showed no significant difference (P = 0.188 and P = 0.394, respectively). Pearson correlation analysis showed that GLS has no correlation with sPAP as evaluated by echocardiography in CTEPH patients (r = − 0.079, P = 0.574), and a weak to moderate correlation with RA area (r = 0.488, P = 0.000), the RV diameter (r = 0.429, P = 0.001), and the RVFW thickness (r = 0.344, P = 0.009). On receiver operating characteristic analysis, GLS has the largest area under the curve to identify RHF when the cutoff value was − 13.45%, the sensitivity was 78.2%, and the specificity was 84.6%, separately. Our study demonstrated that the depression of regional LS of RVFW is more pronounced in the basal and middle segments in CTEPH patients. Also, the longitudinal movement is much more important than the transverse movement when evaluating RV systolic function. As compared with conventional parameters, RVFW GLS showed more sensitivity to identify abnormal RV function and had the largest AUC for identifying RHF. Additionally, GLS showed no correlation with sPAP and a weak correlation with right heart morphological parameters in our CTEPH cohort.

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension

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

Resultados de la tromboendarterectomía pulmonar en la hipertensión pulmonar tromboembólica crónica

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

Investigation of prognostic effect of red cell distribution width on chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism

Objective To investigate the clinical characteristics of acute pulmonary embolism in the elderly and its differences between the elderly and non-elderly patients, and explore the predictive effect of red blood cell distribution width(RDW)on chronic thromboembolic pulmonary hypertension(CTEPH)in patients with acute pulmonary embolism. Methods A total of 129 consecutive patients with acute pulmonary embolism admitted into Affiliated Hospital of Binzhou Medical College were selected from Jan.2009 to Dec.2013.Clinical data including the basic data, blood routine test, blood gas analysis, Doppler echocardiography during admission were retrospectively analyzed.All the patients were followed-up.Ancillary findings and changes of the disease were recorded in detail during the follow-up period.SPSS 19.0 was used to analyze the results. Results The incidences of CEPPH and venous thromboembolism(VTE)in APE patients were higher in the elderly than in non-elderly.The mean RDW and pulmonary arterial systolic pressure on admission in APE patients were higher in the elderly than in non-elderly [(14.22±2.11)% vs.(13.48±1.69)%, P=0.033, for mean RDW] and [(54.82±21.77)mmHg vs.(42.20±19.36)mmHg, P=0.010 for pulmonary arterial systolic pressure]. The mean RDW was higher in CTEPH patients than in patients without CTEPH [(16.79±3.08)% vs.(13.68±1.68)%, P=0.016]. Multivariate Logistic analyses showed that the increased RDW level was an independent risk factors for CTEPH in APE patients(OR=1.535, 95% CI: 1.094-2.155, P=0.013). The area under receiver operating characteristics curve(AUC)of RDW level for predicting CTEPH in APE patients was 0.856(95% CI: 0.706-0.987, P<0.001), the corresponding cut-off point was 14.85%, and the sensitivity and specificity were 88.9% and 87.5% respectively. Conclusions The increased RDW level could predict the risk of CTEPH to a certain extent in APE patients. Key words: Pulmonary embolism; Hypertension, pulmonary; Erythrocytes

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism.

Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE). In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA). Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH. CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH.

Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary hypertension in patients with normal echocardiography

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of pulmonary embolism (PE). Taking into account the reported incidence of CTEPH after acute PE, the number of patients with undiagnosed CTEPH may be high. Objectives: We aimed to determine if cardiopulmonary exercise testing (CPET) could serve as complementary tool in the diagnosis of CTEPH and can detect CTEPH in patients with normal echocardiography. Methods: At diagnosis, we analyzed the data of CPET parameters in 42 patients with proven CTEPH and 51 controls, and evaluated the performance of two scores. Results: VE/VCO2 slope, EQO2, EQCO2, P(A-a)O2, end-tidal partial pressure of CO2 at anaerobic threshold (PETCO2) and capillary to end-tidal carbon dioxide gradient [P(c-ET)CO2] were significantly different between patients with CTEPH and controls (p CO2 was the single parameter with the highest sensitivity (85.7%) and specificity (88.2%). A score combining VE/VCO2 slope, P(A-a)O2, P(c-ET)CO2, PETCO2 [4-parameter-CPET (4-P-CPET) score] reached a sensitivity of 83.3% and a specificity of 92.2% after cross-validation. In 42 patients with CTEPH, echocardiography identified PH in 29 patients (69%), but it was normal in 13 patients (31%). All patients with normal or unmeasurable right ventricular systolic pressure had a pathological CPET. Twelve of the 13 patients (92%) were detected by both CPET scores. Conclusion: CPET is a useful noninvasive diagnostic tool for the detection of CTEPH in patients with suspected PH but normal echocardiography. The 4-P-CPET score provides a high sensitivity with the highest specificity.

Cardiopulmonary Exercise Testing to Detect Chronic Thromboembolic Pulmonary Hypertension in Patients with Normal Echocardiography

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of pulmonary embolism (PE). Taking into account the reported incidence of CTEPH after acute PE, the number of patients with undiagnosed CTEPH may be high. Objectives: We aimed to determine if cardiopulmonary exercise testing (CPET) could serve as complementary tool in the diagnosis of CTEPH and can detect CTEPH in patients with normal echocardiography. Methods: At diagnosis, we analyzed the data of CPET parameters in 42 patients with proven CTEPH and 51 controls, and evaluated the performance of two scores. Results: V<smlcap>E</smlcap>/V<smlcap>CO</smlcap>₂ slope, EQ<smlcap>O</smlcap>₂, EQ<smlcap>CO</smlcap>₂, P(A-a)<smlcap>O</smlcap>₂, end-tidal partial pressure of CO₂ at anaerobic threshold (PET<smlcap>CO</smlcap>₂) and capillary to end-tidal carbon dioxide gradient [P(c-ET)<smlcap>CO</smlcap>₂] were significantly different between patients with CTEPH and controls (p < 0.001). P(c-ET)<smlcap>CO</smlcap>₂ was the single parameter with the highest sensitivity (85.7%) and specificity (88.2%). A score combining V<smlcap>E</smlcap>/V<smlcap>CO</smlcap>₂ slope, P(A-a)<smlcap>O</smlcap>₂, P(c-ET)<smlcap>CO</smlcap>₂, PET<smlcap>CO</smlcap>₂ [4-parameter-CPET (4-P-CPET) score] reached a sensitivity of 83.3% and a specificity of 92.2% after cross-validation. In 42 patients with CTEPH, echocardiography identified PH in 29 patients (69%), but it was normal in 13 patients (31%). All patients with normal or unmeasurable right ventricular systolic pressure had a pathological CPET. Twelve of the 13 patients (92%) were detected by both CPET scores. Conclusion: CPET is a useful noninvasive diagnostic tool for the detection of CTEPH in patients with suspected PH but normal echocardiography. The 4-P-CPET score provides a high sensitivity with the highest specificity.

Red cell distribution width predicts chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism in a long-term follow-up

Red cell distribution width predicts chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism in a long-term follow-up