Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service.

OBJECTIVES: This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Retrospective observational study. SETTING: Pulmonary hypertension referral centre in the UK. PARTICIPANTS: Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed. RESULTS: Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6-18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients. CONCLUSIONS: Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Cost drivers in endovascular pulmonary embolism interventions.

AIM: To determine the costs associated with endovascular pulmonary embolism (PE) interventions. MATERIALS AND METHODS: Procedural costs were determined utilising time-driven activity-based costing (TDABC). A multidisciplinary team created process maps describing personnel, space, equipment, materials, and time required for each procedural step. Costs and capacity cost rates were determined using institutional and publicly available financial data. RESULTS: Process maps were developed for catheter-directed thrombolysis (CDT), ultrasound-assisted thrombolysis (USAT), pharmaco-mechanical thrombectomy (PMT), mechanical-aspiration thrombectomy (MAT), and aspiration thrombectomy (AT). Total costs were CDT $3,889, USAT $9,017.10, PMT $9,565.98, AT $12,126.42, and MAT $13,748.01. Tissue plasminogen activator costs represented 46.4% of the total materials cost for CDT, 13.1% for PMT, and 10.8% for USAT. Intensive care unit costs constitute 33.4% in CDT, 13.5% in USAT, and 13.1% in PMT of the total procedure costs. Highest total procedural costs were AT and MAT with materials cost comprising 82.6% and 80.3% of total costs, respectively. CONCLUSION: Costs were greatest with large-bore mechanical aspiration and least with catheter-directed thrombolysis using a multi-side hole infusion catheter. In the absence of a reference standard technique, physician-driven device selection can substantially impact the price of a procedure. Device choice and costs must be weighed against long-term technical and clinical success to maximise the healthcare value equation.

Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.

Early postoperative pulmonary complications after minimally invasive esophagectomy in the prone position: incidence and perioperative risk factors from the perspective of anesthetic management.

OBJECTIVES: To investigate the incidence of and the risk factors for early postoperative pulmonary complications (PPC) after minimally invasive esophagectomy (MIE) in the prone position from the perspective of anesthetic management. METHODS: We conducted a historical cohort study of patients who underwent MIE in the prone position between September 2010 and August 2018. PPC was defined as pneumonia, atelectasis, acute respiratory distress syndrome (ARDS), respiratory failure, and pulmonary embolism (Clavien-Dindo Classification Grade II or higher) that occurred within 7 days after MIE. RESULTS: Out of 489 patients, there were 90 patients (18.4%) with PPC: 75 patients with pneumonia, 24 patients with atelectasis, 13 patients with respiratory failure, 6 patients with ARDS, and 2 patients with pulmonary embolism. Twenty-eight patients suffered from 2 or more components of PPC. PPC patients were older (66.6 vs. 63.6 year, P = 0.038) and had higher amount of crystalloid (4200 vs. 3550 mL, P < 0.0001), and longer duration of anesthesia (670 vs. 625 min, P = 0.0062) than non-PPC patients. PPC patients were more likely to have had chronic obstructive pulmonary disease (COPD) (26.7 vs. 7.8%, P < 0.001). Incidence of PPC was significantly higher in patients with one-lung ventilation than with two-lung ventilation (37.1 vs. 15.3%, P < 0.001). Multivariable logistic regression analysis showed that PPC was associated with age (per 10 years, odds ratio (OR) = 1.41), COPD (OR = 3.43), one-lung ventilation (OR = 1.94), and volume of crystalloid (per 500 mL, OR = 1.22). CONCLUSIONS: Two-lung rather than one-lung ventilation should be chosen and fluid overload should be avoided in patients undergoing MIE in the prone position.

Proposition of quantitative parameters for pre- and early post-operative assessment in pulmonary thromboendarterectomy - An Indian prospective study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension results from the incomplete resolution of the vascular obstruction associated with pulmonary embolism. Symptoms are exertional dyspnoea and fatigue, and over a period of time, right ventricular dysfunction sets in. Pulmonary thromboendarterectomy is an effective surgical remedy for this condition. Our study is an initial post-operative experience of pulmonary thromboendarterectomy and we have also tried to formulate quantitative parameters for the prediction of the post-operative course in patients who are undergoing surgery. METHODS: Twenty patients with chronic thromboembolic pulmonary hypertension underwent pulmonary thromboendarterectomy between July 2017 and January 2020. Pre-operatively, each patient was subjected to the (i) 6-min walk test, (ii) pre-operative brain natriuretic peptide values and (iii) pulmonary artery systolic pressure. Following the surgery and subsequent discharge, the patients were followed up at intervals of 15 days, 1, 3, 6, 9 months and at 1 year. At one year post-operatively, the same three quantitative tests were performed on each subject. RESULTS: Post-operatively, the mean 6-min walk distance was 499.75 m as against 341.35 m pre-operatively (p < 0.0001). Mean brain natriuretic peptide was 8.69 pm/l as against 47.58 pm/l pre-operatively (p < 0.0001). Mean pulmonary artery systolic pressure was 22.25 as against 67.1 pre-operatively (p < 0.0001). CONCLUSION: 6-Min walk test, brain natriuretic peptide and pulmonary artery systolic pressure could be considered as useful predictors of the haemodynamic severity of disease and predict the post-operative outcome.

Hospital costs of Balloon Pulmonary Angioplasty (BPA) procedure and management for CTEPH patients: An observational study based on the French national hospital discharge database (PMSI).

INTRODUCTION: Since 2014, Balloon Pulmonary Angioplasty (BPA) has become an emerging and complementary strategy for chronic thromboembolic hypertension (CTEPH) patients who are not suitable for pulmonary endarterectomy (PEA) or who have recurrent symptoms after the PEA procedure. OBJECTIVE: To assess the hospital cost of BPA sessions and management in CTEPH patients. METHODS: An observational retrospective cohort study of CTEPH-adults hospitalized for a BPA between January 1st, 2014 and June 30th, 2016 was conducted in the 2 centres performing BPA in France (Paris Sud and Grenoble) using the French national hospital discharge database (PMSI-MCO). Patients were followed until 6 months or death, whichever occurred first. Follow-up stays were classified as stays with BPA sessions, for BPA management or for CTEPH management based on a pre-defined algorithm and a medical review using type of diagnosis (ICD-10), delay from last BPA procedure stay and length of stay. Hospital costs (including medical transports) were estimated from National Health Insurance perspective using published official French tariffs from 2014 to 2016 and expressed in 2017 Euros. RESULTS: A total of 191 patients were analysed; mainly male (53%), with a mean age of 64,3 years. The first BPA session was performed 1.1 years in median (IQR 0.3-2.92) after the first PH hospitalisation. A mean of 3 stays with BPA sessions per patient were reported with a mean length of stay of 8 days for the first stay and 6 days for successive stays. The total hospital cost attributable to BPA was € 4,057,825 corresponding to €8,764±3,435 per stay and €21,245±12,843 per patient. Results were sensitive to age classes, density of commune of residence and some comorbidities. CONCLUSIONS: The study generated robust real-world data to assess the hospital cost of BPA sessions and management in CTEPH patients within its first years of implementation in France.

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0.91 ± 0.15 ( p < 0.01), respectively. Conclusion Ultrasound-accelerated catheter-directed thrombolysis is a safe and efficacious treatment for submassive pulmonary embolism. It reduces pulmonary hypertension and improves right ventricular function in patients with submassive pulmonary embolism.

Clinical Characteristics and Prognosis of Pulmonary Embolism Caused by Economy Class Syndrome. / Características clínicas y pronóstico de la tromboembolia pulmonar secundaria al síndrome de clase turista.

OBJECTIVE: Clinical presentation and short-term prognosis of patients with travel-associated acute pulmonary embolism (PE) (i.e., economy class syndrome [ECS]) is not well understood. METHODS: In this retrospective cohort study of patients with acute PE identified from a single center registry, we assessed the clinical presentation and the association between ECS and the outcomes of all-cause mortality, PE-related mortality, nonfatal venous thromboembolism and nonfatal major bleeding rates through 30days after initiation of PE treatment. RESULTS: Of the 2,333 patients with acute symptomatic PE, 124 (5.3%; 95% confidence interval, 4.4-6.3%) had ECS. Patients with ECS were younger and had fewer comorbid diseases (recent bleeding, chronic obstructive pulmonary disease, congestive heart failure), but they presented with more signs of clinical severity (syncope [48% vs. 14%; P<.001], tachycardia [37% vs. 21%; P<.001], right ventricular dysfunction [31% vs. 19%; P<.01] and myocardial injury [57% vs. 28%; P<.001]) compared to those without ECS. Regression analyses showed a significantly lower risk of all-cause mortality for patients with ECS compared to patients without ECS (1.6% vs. 9.6%; P<.01). We did not detect a difference in PE-related mortality at 30days between those with and those without ECS (0.8% vs. 3.1%; P=.18). CONCLUSIONS: PE patients with ECS are younger and have fewer comorbid diseases compared to those without ECS. Though they present with more signs of clinical severity, their short-term prognosis is excellent.

Comparative assessment of the effectiveness of treatment of pulmonary thromboembolism in elderly patients.

We compared the efficiency of treatment of 99 patientswith pulmonary thromboembolism using thrombolytic agents, surgical intervention, and anticoagulation therapy with heparin and vitamins K. The surgical treatment proved more efficient than the two other options.

Functional assessment and quality of life before and after pulmonary endoarterectomy.

PURPOSE: The study investigates Quality of Life (QOL) and correlation with functional status of patients affected by Chronic Thromboembolic Pulmonary Hypertension who undergo Pulmonary Endoarterectomy. METHODS: We investigated with an observational design (before surgery, three and twelve months afterwards) the hemodynamic data (NYHA class, mean pulmonary arterial pressure, cardiac output and pulmonary vascular resistance), the functional status (using the 6-Minute Walk Test) and the QOL, using three questionnaires: Medical Outcome Study Short Form-36 (SF-36), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Saint George Respiratory Questionnaire (SGRQ). We report the results of forty-nine patients. RESULTS: After surgery there was an improvement on functional and hemodynamic parameters and on QOL. The physical domain (PCS) of SF-36 was weakly but significantly associated with all functional parameters. There was no association between functional parameters and mental domain (MCS) of SF-36 or SGRQ. The improvement in 6-Minute Walk Distance was associated with an increase in MLHFQ. CONCLUSIONS: Both QOL and submaximal exercise tolerance improve after surgery. However only the physical domains of SF-36 appear to be significantly associated to the functional data.

Assessment of left atrial volume before and after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Impaired left ventricular diastolic filling is common in chronic thromboembolic pulmonary hypertension (CTEPH), and recent studies support left ventricular underfilling as a cause. To investigate this further, we assessed left atrial volume index (LAVI) in patients with CTEPH before and after pulmonary thromboendarterectomy (PTE). METHODS: Forty-eight consecutive CTEPH patients had pre- & post-PTE echocardiograms and right heart catheterizations. Parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, LAVI, & mitral E/A ratio. Echocardiograms were performed 6 ± 3 days pre-PTE and 10 ± 4 days post-PTE. Regression analyses compared pre- and post-PTE LAVI with other parameters. RESULTS: Pre-op LAVI (mean 19.0 ± 7 mL/m2) correlated significantly with pre-op PVR (R = -0.45, p = 0.001), mPAP (R = -0.28, p = 0.05) and cardiac index (R = 0.38, p = 0.006). Post-PTE, LAVI increased by 18% to 22.4 ± 7 mL/m2 (p = 0.003). This change correlated with change in PVR (765 to 311 dyne-s/cm5, p = 0.01), cardiac index (2.6 to 3.2 L/min/m2, p = 0.02), and E/A (.95 to 1.44, p = 0.002). CONCLUSION: In CTEPH, smaller LAVI is associated with lower cardiac output, higher mPAP, and higher PVR. LAVI increases by ~20% after PTE, and this change correlates with changes in PVR and mitral E/A. The rapid increase in LAVI supports the concept that left ventricular diastolic impairment and low E/A pre-PTE are due to left heart underfilling rather than inherent left ventricular diastolic dysfunction.

Contrast-enhanced multidetector-row computed tomography vs. Time-resolved magnetic resonance angiography vs. contrast-enhanced perfusion MRI: assessment of treatment response by patients with inoperable chronic thromboembolic pulmonary hypertension.

PURPOSE: To compare therapeutic effect assessment capability of multidetector-row computed tomography (MDCT), magnetic resonance angiography (MRA), and dynamic perfusion MRI for chronic thromboembolic pulmonary hypertension (CTEPH) patients. MATERIALS AND METHODS: Twenty-four consecutive CTEPH patients treated with conventional therapy underwent pre- and posttherapeutic MDCT, MRA, dynamic perfusion MRI, 6-minute walk distance (6-MWD), cardiac ultrasound (US), and right heart catheterization. According to therapeutic results, all patients were divided into response (n = 13) and nonresponse (n = 11) groups. CTEPH indexes for MDCT (CTEPH(CT) ) and MRA (CTEPH(MRA) ) were calculated on the basis of embolic burden. Pulmonary perfusion parameter maps were generated from all perfusion MR data, followed by determination of improvements in mean perfusion parameter at regions of interest (ROIs) for each patient. Receiver operating characteristic (ROC)-based positive tests were performed to determine the feasible threshold values for distinguishing two groups. Finally, diagnostic capabilities were compared by means of McNemar's test. RESULTS: When feasible threshold values adapted, specificity (90.9 〈10/11〉%, P < 0.05) and accuracy (95.8 〈23/24〉%, P < 0.05) for improvement in pulmonary blood flow were significantly higher than those for CTEPH(CTA) (specificity: 36.4 〈4/11〉%, accuracy: 70.8 〈17/24〉%). CONCLUSION: Dynamic perfusion MRI has better capability for assessment of therapeutic effect on CTEPH patients than does MDCT.

Heart-type fatty acid-binding protein for risk assessment of chronic thromboembolic pulmonary hypertension.

Heart-type fatty acid-binding protein (H-FABP) is a reliable marker of myocardial injury and was recently identified as a predictor of outcome in acute pulmonary embolism. The aim of the present study was to investigate the prognostic value of H-FABP in chronic thromboembolic pulmonary hypertension (CTEPH). In total, 93 consecutive patients with CTEPH were studied. During long-term follow-up (median duration 1,260 days, interquartile range (IQR) 708-2,460 days), 46 (49%) patients had an adverse outcome, defined as CTEPH-related death, lung transplantation or persistent pulmonary hypertension after pulmonary endarterectomy (PEA). Baseline H-FABP levels in plasma ranged from 0.69-24.3 ng x mL(-1) (median (IQR) 3.41 (2.28-4.86) ng x mL(-1)). Cox regression analysis revealed a hazard ratio of 1.10 (95% confidence interval 1.04-1.18) for each increase of H-FABP by 1 ng x mL(-1), and continuous elevations of H-FABP emerged as an independent predictor of adverse outcome by multivariable analysis. PEA was performed in 52 patients and favourably affected the long-term outcome. Kaplan-Meier analysis revealed that patients with baseline H-FABP concentrations >2.7 ng x mL(-1), the median value of the biomarker in the surgically treated population, had a lower probability of event-free survival after PEA. Heart-type fatty acid-binding protein is a promising novel biomarker for risk stratification of patients with chronic thromboembolic pulmonary hypertension.

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: short-term functional assessment in a longitudinal study.

AIM: Presently, the surgical treatment choice in chronic thromboembolic pulmonary hypertension (CTEPH) consists in a pulmonary endarterectomy (PEA). The aim of the present study is the functional assessment of patients submitted to PEA both preoperatively and shortly after the intervention. A longitudinal study was developed to study the quality and quantity of functional performance possible in these subjects. METHODS: Twenty-two subjects were assessed immediately prior to PEA and 3 months later in order to obtain quantitative measurements of short-term functional recovery. The functional assessment included the 6-min walk test (6mWT), the measurement of the oxygen percent saturation (HbS%O(2)) and the degree of dyspnea subjectively perceived by each patient. RESULTS: Three months after the surgical intervention, there was a definite increase in the number of meters walked during the 6mWT with respect to preintervention; the difference between the distances walked in the 6mWT (6mWD) in the pre and post-PEA was statistically significant (Paired t-test P<0.001). CONCLUSION: In this study the 6mWT resulted to be a useful tool in the functional evaluation of patients affected by CTEPH and submitted to PEA. The average 6mWD significantly improved already at 3 months after the intervention, thus reaching the minimum limit of the range predicted for the healthy control, but remains lower than the average theoretical value predicted (about 75% of the same).