History Of Acute Pulmonary Embolism Research Articles

Circulatory support with venovenous ECMO in a patient with reperfusion pulmonary edema after pulmonary artery thromboendarterectomy

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by the obstruction of pulmonary arteries secondary to chronic thromboembolism. Pulmonary thromboendarterectomy surgery (PTE) is the main treatment for patients with CTEPH, as it removes the chronic thrombi from the pulmonary arteries. Pulmonary reperfusion syndrome is a common complication of the surgery, which involves the development of pulmonary edema in the area where blood perfusion improves after the surgery. The incidence of this syndrome varies from 8 to 91% depending on the criteria used for diagnosis, and it is one of the most serious complications of pulmonary thromboendarterectomy. In such cases, circulatory support with extracorporeal membrane oxygenation (ECMO) has become a valuable therapeutic modality. We present the case of a 60-year-old woman with a history of acute pulmonary embolism due to deep vein thrombosis of the right pelvic limb who was diagnosed later with CTEPH who was admitted for scheduled surgical treatment involving bilateral PTE. However, during the immediate postoperative period, she developed cardiogenic shock and refractory hypoxemia secondary to pulmonary reperfusion syndrome following the surgical procedure. As a result, she required veno-venous ECMO circulatory support for 6 days, leading to resolution of the pulmonary condition and clinical improvement.

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.

Chronic thromboembolic disease is associated with exercise-induced pulmonary hypertension and functional right ventricle deterioration

Abstract Background and Aim Chronic thromboembolic pulmonary disease (CTED) is a progressive disease caused by a wall-adherent, fibrotic thrombus in the pulmonary circulation persisting despite oral anticoagulation and despite vascular remodeling of the small arteries. Despite normal pulmonary hemodynamics at rest, exercise intolerance and dyspnea have been reported. Drivers and risk factors, as well as the clinical impact of CTED, are not yet adequately characterized. We evaluated clinical factors predictive of the development of postthrombotic pulmonary disease in a cohort of patients with a history of acute pulmonary embolism on oral anticoagulant therapy. We also evaluated its impact on functional capacity, pulmonary haemodinamics at rest and after exercise and right ventricle morphology and function. Methods We compared 33 consecutive patients with a history of acute pulmonary embolism and normal pulmonary vascular imaging (group 1, n=16) or persistent defects on perfusion scan (positive P scan) despite therapeutic anticoagulation for 4 months (group 2, n=17), for the following parameters: 1. Thrombotic load (extension of pulmonary thromboembolism on CT angiography) and Pulmonary Embolism Severity Index (PESI) score at the time of admission to the Intensive Care Unit (ICU); 2. Presence of thrombophilia (factor V Leiden, prothrombin variant, lupus anticoagulant); 3. Cardiovascular risk factors; 4. Anthropometric and demographic parameters; 5. Anticoagulation treatment in ICU and at discharge. The two groups of patients were also compared for the World Health Organization functional class (WHO-FC), NT-proBNP, cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and after 24 months. Results Compared with group 1, patients with persisting perfusion defects (group 2) featured higher thrombotic load (p=0.004) and PESI score (p=0.02) at the time of ICU admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p&amp;lt;0.001) and ESE (p&amp;lt;0.001). At the 24 months follow-up group 2 showed higher NT-proBNP (p&amp;lt;0.001) and WHO-FC (p&amp;lt;0.001), systolic (p&amp;lt;0.001) and diastolic (p=0.037) right ventricular (RV) dysfunction and worse echo indices of RV-Arterial Coupling (TAPSE/PAPs (p&amp;lt;0.001)), despite maintaining a low or intermediate echocardiographic probability of PH (Table 1). Conclusions Despite the low and intermediate echocardiographic probability of PH, patients with persistent positive P scan had reduced functional capacity, and developed ExPH and RV functional deterioration.

Kussmaul’s Sign- In a patient with Severe PAH

The patient is a 33 years old male who had a history of acute pulmonary embolism three and a half years back. He had received thrombolysis with alteplase and was subsequently on oral anticoagulants. After one year of the index episode, the patient started to experience progressive worsening of breathlessness. Further evaluation led to the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Patient was offered pulmonary endarterectomy which he declined and preferred medical management. He did not show clinical improvement and eventually developed refractory heart failure. And patient presented to Emergency department (ED) with worsening of breathlessness. On presentation to the ED, patient was in distress with pulse of 110/min, BP of 100/60 with no evidence of pulsus paradoxus, Respiratory rate of 22/min and chest was revealing bilateral basal crepts and CVS examination revealed pansystolic mummer at left parasternal edge. JVP was elevated and showed only one prominent outward crest, which is a prominent CV wave and one dominant downward trough, a prominent Y descent, and there was a paradoxical rise in the JVP on inspiration (video 1) which is an important clinical sign in heart failure commonly known by the eponym Kussmaul’s sign. The prominent CV wave in this paitent reflected sever Tricuspid regurigitation (TR). On echo, patient had severe RV dysfunction with severe TR with Pulmonary hypertension. Patient was treated with intravenous diuretics, and pulmonary vasodilators and improved symptomatically and was referred for work up for heart-lung transplantation.

Baseline Clinical Characteristics and Incidence of Chronic Thromboembolic Pulmonary Hypertension Patients in Latvia, 2019-2020.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and progressive condition; however, the true characteristics of CTEPH are still unknown, as notable regional variations exist in terms of patients' age, baseline hemodynamic data, and management choices. This report aims to investigate the baseline clinical characteristics, incidence, and risk factors associated with CTEPH patients in Latvia from 2019 to 2020. Methods: The data were analyzed from a prospective, nationwide, Latvian pulmonary hypertension registry for incident CTEPH cases. The patients' clinical characteristics were assessed at the time of diagnosis. Results: During the course of this study, a cohort of 13 patients with CTEPH were included for analysis. Among the enrolled CTEPH patients, most exhibited low exercise and functional capacity, with a median (±IQR) 6 min walk distance of 300.0 (±150.0) m. The median values (±IQR) for mean pulmonary artery pressure and pulmonary vascular resistance were 40.0 ± 13.0 mmHg and 7.35 ± 2.82 Wood units, respectively. The most common risk factors for CTEPH were a history of acute pulmonary embolism and a blood group other than O. Conclusions: The findings of this report revealed the characteristics of the Latvian CTEPH population, indicating that a significant proportion of patients are elderly individuals with multiple comorbidities.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry.

BackgroundPulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context.Methods1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation–perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation.ResultsOverall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA).ConclusionsThe registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.

Results From the United States Chronic Thromboembolic Pulmonary Hypertension Registry: Enrollment Characteristics and 1-Year Follow-up

BackgroundThe 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 QuestionWhat are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects?Study Design and MethodsThis 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.ResultsMost 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).InterpretationDifferences 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 RegistrationClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.

Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension.

BackgroundAlthough chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE) share some clinical manifestations, a limited proportion of patients with CTEPH have a history of APE. Moreover, in histopathologic studies, it has been revealed that pulmonary vasculature lesions similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, it remains unknown whether these 3 disorders also share genetic backgrounds.Methods and ResultsWhole exome screening was performed with DNA isolated from 51 unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic variants associated with pulmonary arterial hypertension or APE in patients with CTEPH was compared with those in the integrative Japanese Genome Variation Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous variants in patients with CTEPH. Although we found 6 nonsynonymous variants that are associated with APE in patients with CTEPH, there was no nonsynonymous variant associated with pulmonary arterial hypertension. Patients with CTEPH with a history of APE had nonsynonymous variants of F5, which encodes factor V. In contrast, patients with CTEPH without a history of APE had a nonsynonymous variant of THBD, which encodes thrombomodulin. Moreover, thrombin‐activatable fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was significantly more activated in those who had the variants of THBD compared with those without it.ConclusionsThese results provide the first evidence that patients with CTEPH have some variants associated with APE, regardless of the presence or absence of a history of APE. Furthermore, the variants might be different between patients with CTEPH with and without a history of APE.

P4678The hemodynamic improvement with balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension depends on the lesion location

Abstract Background Pulmonary endarterectomy (PEA) is a treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Patients with proximal pulmonary artery disease are considered to be good candidates for PEA because of their generally excellent outcomes. However, not all patients can be operated because of patients' advanced age, comorbidities and poor general condition. Balloon pulmonary angioplasty (BPA) has become an alternative treatment for CTEPH patients especially whose lesions locate in the distal site. The effectiveness of BPA in patients who have lesions in the proximal pulmonary arteries but cannot be a candidate for PEA remains unclear. Purpose The aim of this study was to investigate the outcome of BPA in CTEPH patients whose lesions appears operable but ineligible for PEA. Methods A total of 370 patients who underwent BPA in our institute from November 2004 to January 2018 were enrolled. All the patients were divided into operable group and inoperable group according to the difference of lesion location based on the findings of perfusion scintigraphy, computed tomography and pulmonary angiography. Hemodynamic effects of BPA in both groups were investigated. We also conducted survival analyses using the Kaplan-Meier method with the log-rank test. Results Among 370 patients, 90 patients deemed operable. The main reasons why not operated in the PEA operable group were patient's refusal (44%), advanced age (14%), and comorbidities (27%). There were no baseline characteristic differences between two groups except for the history of acute pulmonary embolism. Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) equally improved after BPA in both groups (operable: 38.2±10.8 mmHg to 21.5±4.7mmHg, inoperable: 42.4±11.3 mmHg to 21.8±4.8 mmHg, p&lt;0.001, operable: 8.0±4.2 wood unit to 3.5±1.5 wood unit, inoperable: 9.1±4.6 wood unit to 3.4±1.3 wood unit, p&lt;0.001). Furthermore, five-year cumulative survival rates were not different between two groups (inoperable vs. operable: 93% vs. 88%, p=0.23, median follow-up period was 23.0 months (range: 5–136 months)). Meanwhile, the absolute change of mPAP and PVR in inoperable group were greater than those in operable group (inoperable: 20.7±11.2 mmHg, operable: 16.6±11.0 mmHg, p=0.010, inoperable: 5.6±4.4 wood unit, operable: 4.5±3.9 wood unit, p=0.015). Conclusions Although the outcome of BPA for CTEPH patients with operable lesions appears acceptable, absolute change in hemodynamics was lower than that of the patients with inoperable lesions. CTEPH with proximal lesions should be treated with PEA rather than BPA.

Recent Advances in the Understanding of Thrombosis.

Recent Advances in the Understanding of Thrombosis.

Are We Overdiagnosing Pulmonary Embolism? “No”

Diagnosis of acute pulmonary embolism currently relies on computed tomography angiography which is acknowledged as a powerful, noninvasive tool. The concept of overdiagnosis is counterbalanced by a series of unanswered questions regarding the natural history of acute pulmonary embolism and the missing links between acute and chronic thromboembolic disease. For numerous reasons, it is less than certain that this concept will survive.

Sensitivity of a Simple Noninvasive Screening Algorithm for Chronic Thromboembolic Pulmonary Hypertension after Acute Pulmonary Embolism.

Background Recently, we constructed a noninvasive screening algorithm aiming at earlier chronic thromboembolic pulmonary hypertension (CTEPH) detection after acute pulmonary embolism (PE), consisting of a prediction score and combined electrocardiography (ECG)/N-terminal pro-brain natriuretic peptide (NT-proBNP) assessment. The aim of this study was to confirm the algorithm's sensitivity for CTEPH detection and to evaluate the reproducibility of its individual items. Methods Two independent researchers calculated the prediction score in 54 consecutive patients with a history of acute PE and proven CTEPH based on clinical characteristics at PE diagnosis, and evaluated the ECG and NT-proBNP level assessed at the moment of CTEPH diagnosis. Interobserver agreement for the assessment of the prediction score, right-to-left ventricle (RV/LV) ratio measurement on computed tomography pulmonary angiography, as well as ECG reading was evaluated by calculating Cohen's kappa statistics. Results Median time between PE diagnosis and presentation with CTEPH was 9 months (interquartile range: 5–15). The sensitivity of the algorithm was found to be 91% (95% confidence interval [CI]: 79–97%), indicating that 27 of 30 cases of CTEPH would have been detected when applying the screening algorithm to 1,000 random PE survivors with a 3% CTEPH incidence (projected negative predictive value: 99.7%; 95% CI: 99.1–99.9%). The interobserver agreement for calculating the prediction score, RV/LV ratio measurement, and ECG reading was excellent with a kappa of 0.96, 0.95, and 0.89, respectively. Conclusion The algorithm had a high sensitivity of 91% and was highly reproducible. Prospective validation of the algorithm in consecutive PE patients is required before it can be used in clinical practice.

Manejo de la hipertensión pulmonar tromboembólica crónica. Experiencia de un centro de referencia nacional

IntroductionAlthough medical treatment can clinically improve inoperable patients, pulmonary endarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension, and is potentially curative. An evaluation was made of the long-term outcomes in medical and surgical populations at a national Unit of Reference. MethodsA total of 292 patients were evaluated from February 1996 until December 2015, of whom 142 were had surgery (group 1) and 116 were considered inoperable (group 2). The follow-up ended in December 2016. ResultsSurvival rate after 3 3years was 92% in group 1 and 86% in group 2, and after 5 5years it was 91% and 78%, respectively (P=.001). The multivariate analysis results showed that survival in patients with chronic thromboembolic pulmonary hypertension was related to surgery (HR 0.37; 95% CI; 0.19-0.72; P=.003), history of acute pulmonary embolism (HR 0.50; 95% CI; 0.27-0.92; P=.026), distance walked in the six-minute walk test (HR 0.79; 95% CI; 0.73-0.85; P=.001), history of cancer (HR 2.57; 95% CI; 1.22-5.43; P=.013), and pulmonary vascular resistance (HR 1.19; 95% CI; 1.02-1.39; P=.024). In group 1, the variables associated with survival were the six-minute walk test (HR 0.84; 95% CI; 0.79-0.96; P=.009), and the cardiac output (HR 0.61; 95% CI; 0.39-0.96; P=.033), and in group 2, the variable associated was the six-minute walk test (HR 0.81; 95% CI; 0.71-0.92; P=.001). ConclusionPatients with chronic thromboembolic pulmonary hypertension who received pulmonary endarterectomy surgery have an excellent survival rate, and significantly superior to that of patients treated medically. In the present series, pulmonary endarterectomy surgery was the most important predictive survival factor.

Epidemiology of chronic thromboembolic pulmonary hypertension in Korea: results from the Korean registry.

Background/Aims:The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is difficult for numerous reasons and is related with a poor prognosis. In Korea, the incidence of CTEPH and its clinical features are unknown. Thus, in this study, we evaluated the clinical characteristics and outcomes of CTEPH in a Korean cohort.Methods:This study included South Korean patients diagnosed with CTEPH between September 2008 and October 2011. Baseline characteristics, treatments and outcomes were analyzed.Results:A total of 134 patients were included in this study with 76 females (56.7%). Their median age was 58.3 ± 15.9 years and dyspnea (112 patients, 83.5%) was the most common presenting symptom. Sixty-three patients (47%) had a history of acute pulmonary embolism or deep vein thrombosis, and six (4.5%) had pulmonary tuberculosis. In total, 28 patients (21%) underwent pulmonary thromboendarterectomy (PTE), and 99 patients had medical therapy. During the study period, 18 patients (13.4%) died. In a multivariate analysis, higher hemoglobin (relative risk [RR], 1.516; 95% confidence interval [CI], 1.053 to 2.184; p = 0.025) and lower total cholesterol levels (RR, 0.982; 95% CI, 0.965 to 0.999; p = 0.037) were associated with increased mortality.Conclusions:This was the first national cohort study of Korean patients with CTEPH. Accurate diagnosis, characterization and distributions of CTEPH are imperative for prompt treatment in patients, particularly those undergoing PTE.

The lowest VE/VCO2 ratio best identifies chronic thromboembolic pulmonary hypertension

IntroductionThe natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH. Methods15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET. ResultsThe lowest VE/VCO2 was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4L/min vs 29.9L/min vs 27.1L/min, p<0.005). The VE/VCO2 slope (48.4L/min/L/min vs 29.9L/min/L/min vs 28.0L/min/L/min, p<0.005) and oxygen uptake efficiency plateau (OUEP) (37.1L/min vs 27.0L/min vs 25.2L/min, p<0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO2≥34.35L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p<0.001). The lowest VE/VCO2 was higher in chronic PE patients compared with the controls (29.9L/min vs 26.5L/min, p<0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients. ConclusionsCTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.

Chronic thromboembolic pulmonary hypertension: Time delay from onset of symtoms to diagnosis and clinical condition at diagnosis

Chronic-thromboembolic pulmonary hypertension (CTEPH) is a serious complication of acute pulmonary embolism (PE). In untreated patients prognosis is poor. It depends on WHO-functional class. A delay from onset of symptoms and diagnosis can lead to a further worsening of prognosis. A pulmonary endarterectomy is the treatment of choice. We aimed to evaluate the time delay from onset of symptoms to diagnosis and the WHO-functional class at primary diagnosis in patients with CTEPH. Retrospective analysis of data from 70 monocentrically registered patients (48 women, 22 men, mean age 66,2 years ± 13,8 years) with confirmed CTEPH from the pulmonary hypertension expert center Missionsärztliche Klinik. Diagnostic work-up was performed according to the current guidelines. Mean delay from onset of symptoms to diagnosis of CTEPH was 18 ± 26 months. Time delay was only slightly shorter in patients with a history of PE (n = 56; 81 %) than in patients without a history of PE (n = 13; 19 %): 16,9 ± 23,8 vs. 23,5 ± 36,9 months. Time delay was higher in patients who received vasoactive medication before the first contact with a PH expert center and in patients who were classified as technically not suitable for a thrombendarterectomy. 38 patients with a history of acute PE did not have a period without symptoms. In 18 patients symptoms had transiently gone after PE. More than 70 % presented in WHO functional class III or IV. Time delay between onset of symptoms and diagnosis of CTEPH and referral to a PH expert center is long and the majority of patients presented in WHO-functional class III or IV. Prognosis is poor in untreated patients and getting worse with a higher WHO-functional class. For this reason, and because CTEPH can be cured by a pulmonary endarterectomy, each patient with suspected PH should be referred to a PH expert center to exclude CTEPH.

A 35-year old man with dyspnea on exertion, history of acute pulmonary embolism and ischaemic stroke

We present a case of a 35-year old man with a history of an acute pulmonary embolism and ischaemic stroke, who after several weeks of adequate antithrombotic treatment experienced functional deterioration with severe dyspnea and haemoptysis. Detailed evaluation reveled chronic thromboembolic pulmonary hypertension, deep vein thrombosis of his right thigh and patent foramen ovale. No laboratory signs of a hypercoagulable conditions were found. After through assessment the patient was referred for pulmonary endarterectomy and patent foramen ovale closure. Both procedures were performed successfully with the significant improvement in patient’s clinical status. Patient remained clinically stable with no signs of right ventricle dysfunction in the follow-up. This article provides details regarding etiopathogenesis, clinical features and diagnostic evaluation of chronic thromboembolic pulmonary hypertension related to an acute pulmonary embolism. It covers the latest guidelines for screening and therapy as well as information regarding innovations in health care, and social care. JRCD 2012; 1: 24–29 Key words: Pulmonary embolism; Chronic thromboembolic pulmonary hypertension; Pulmonary endarterectomy

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Background— Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. Methods and Results— The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%– 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension–targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. Conclusions— Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension–targeted treatments.

Importance of Clinical and Echocardiographic Hemodynamic Assessment in Chronic Pulmonary Embolism

We describe a 42-year-old man presenting to the emergency department with cardiogenic shock. He had a prior history of acute pulmonary embolism (PE), and had been on anticoagulation for 2 years. Although computed tomographic pulmonary angiography performed at the emergency department showed no change in the extent of PE and did not support a role of surgical treatment, pulmonary embolectomy was recommended by attending physician based on clinical and echocardiographic hemodynamic findings like unstable vital sign and markedly enlarged right ventricle with severely depressed systolic function. Surgery confirmed the presence of fresh thrombi. After surgery, hemodynamic status was progressively improved, but the patient died due to pneumonia and pulmonary hemorrhage.