Pulmonary endarterectomy for subacute on top of chronic thromboembolic disease.

Our objective is to describe our approach for a case of subacute on top of chronic thromboembolic disease and highlight operative learning points. Prior to incision, appropriate monitoring equipment, including an arterial line, Swan-Ganz catheter, brain saturation monitor and bispectral index monitor, is placed for proper management of haemodynamics. Sternotomy was performed, and the ascending aorta was cannulated, followed by bicaval cannulation for venous drainage. The patient was cooled to deep hypothermia. Once target temperature was achieved, circulatory arrest commenced. The left pulmonary artery was opened and the subacute component was removed without disrupting the plane of the chronic thromboembolic disease. An endarterectomy plane was then created proximally and dissected into the distal segmental/subsegmental branches. Once the endarterectomy was completed, the left pulmonary artery was closed. Circulation was resumed for end-organ perfusion. Once the right pulmonary artery was ready for dissection, circulatory arrest was restarted. Similarly to the left side, the subacute component was removed without disrupting the plane of the chronic thromboembolic disease. An endarterectomy plane was then created proximally and dissected into the distal segmental/subsegmental branches. Circulation was then resumed. Once rewarmed to 35.5°C, the patient was decannulated and the sternum was closed.

Unilateral Chronic Thromboembolic Pulmonary Disease: Do Patients Benefit From Thromboendarterectomy? Case Series From Three CTEPH Centres.

BACKGROUND: Unilateral chronic thromboembolism pulmonary disease (CTEPD) is very rare. There is limited information on the safety and efficacy of pulmonary endarterectomy (PEA) in this population. This study investigated the effectiveness of PEA in this unique disease. METHODS: This multicentre study included patients with unilateral CTEPD from three referral centres in the United States, Turkey, and Iran. The patients' demographic information, 6-minute walk test distance (6MWD), New York Heart Association (NYHA) functional class, and haemodynamics were evaluated. RESULT: Of the 1,031 patients who had undergone PEA, 39 patients (3.7%) had pure unilateral involvement, of whom 28 were female (71.8%). There was a significant improvement in the mean pulmonary artery pressure (mPAP, 26 mmHg vs 21 mmHg; p=0.011) and pulmonary vascular resistance (PVR, 202 vs 136 dynes∗sec1∗cm-5; p=0.014). There was also a significant improvement in NYHA functional class (p<0.001) and 6MWD (360 vs 409 m; p<0.001). In the nine patients with normal haemodynamic parameters at rest, there was no significant change in median 6MWD (448.5 vs 449 m; p=0.208), mPAP (19 mmHg vs 16.5 mmHg; p=0.397), and PVR (129 vs 84.5 dynes∗sec1∗cm-5; p=0.128). The most common postoperative complication was ipsilateral pleural effusion. One patient needed extracorporeal membrane oxygenation support. No patient died within the 1-year follow up. CONCLUSION: Pulmonary endarterectomy is a safe and effective procedure for improving the symptoms and haemodynamic parameters of patients with unilateral CTEPH. Symptomatic patients with unilateral chronic thromboembolic disease are suitable for PEA.

Treatment and management of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital-based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow-up practices. Prescription of pulmonary arterial hypertension-specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center-specific experience and region-specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.

Recognition, diagnosis, and operability assessment of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross-sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the recognition and diagnosis of CTEPH and the referral and evaluation of these patients. The survey was offered to hospital-based medical specialists through Scientific Societies and other medical organizations, from September 2021 to May 2022. Response data from 353 physicians showed that self-reported awareness of CTEPH increased over the past 10 years among 96% of respondents. Clinical practices in acute pulmonary embolism (PE) follow-up and CTEPH diagnosis differed among respondents. While 50% of respondents working in a nonexpert center reported to refer patients to an expert pulmonary hypertension/CTEPH center when CTEPH is suspected, 51% of these physicians did not report referral of patients with a confirmed diagnosis for further evaluation. Up to 50% of respondents involved in the evaluation of referred patients have concluded a different operability status than that indicated by the referring center. This study indicates that early diagnosis and timely treatment of CTEPH is challenged by suboptimal acute PE follow-up and patient referral practices. Nonadherence to guideline recommendations may be impacted by various barriers to care, which were shown to vary by geographical region.

A Novel Dual Energy Computed Tomography Score Correlates With Postoperative Outcomes in Chronic Thromboembolic Pulmonary Hypertension.

PURPOSE: To compare dual-energy computed tomography (DECT) based qualitative and quantitative parameters in chronic thromboembolic pulmonary hypertension with various postoperative primary and secondary endpoints. MATERIALS AND METHODS: This was a retrospective analysis of 64 patients with chronic thromboembolic pulmonary hypertension who underwent DECT. First, a clot score was calculated by assigning the following score: pulmonary trunk-5, each main pulmonary artery-4, each lobar-3, each segmental-2, and subsegmental-1 per lobe; the sum total was then calculated. The perfusion defect (PD) score was calculated by assigning 1 point to each segmental PD. The combined score was calculated by adding clot and PD scores. For quantitative evaluation, we calculated perfused blood volume (PBV) (%) of each lung and the sum of both lungs. Primary endpoints included testing association between combined score and total PBV with change in mean pulmonary arterial pressure ([mPAP], change calculated as preop minus postop values). Secondary endpoints included explorative analysis of the correlation between combined score and PBV with change in preoperative and postoperative pulmonary vascular resistance, change in preoperative 6-minute walk distance (6MWD), and immediate postoperative complications such as reperfusion edema, ECMO placement, stroke, death and mechanical ventilation for more than 48 hours, all within 1 month of surgery. RESULTS: Higher combined scores were associated with larger decreases in mPAP ( =0.27, P =0.036). On average, the decrease in mPAP (pre mPAP-post mPAP) increased by 2.2 mm Hg (95% CI: -0.6, 5.0) with each 10 unit increase in combined score. The correlation between total PBV and change in mPAP was small and not statistically significant. During an exploratory analysis, higher combined scores were associated with larger increases in 6MWD at 6 months postprocedure ( =0.55, P =0.002). CONCLUSION: Calculation of DECT-based combined score offers potential in the evaluation of hemodynamic response to surgery. This response can also be objectively quantified.

Lessons learned in developing a chronic thromboembolic pulmonary hypertension program.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) is a deadly underdiagnosed form of pulmonary hypertension, traditionally treated with surgical extraction of thrombo-fibrotic lesions via pulmonary thrombendarterectomy (PTE) surgery. More recently, treatment options have expanded to pulmonary vasodilator medical therapy and balloon pulmonary angioplasty (BPA). This has led to increased awareness and detection of CTEPH, as well as growing interest in performing PTE and BPA. This review will describe the steps required to build a successful CTEPH team in the context of the rapidly evolving treatment of CTEPH. RECENT FINDINGS: CTEPH care requires a multidisciplinary team, including a Pulmonologist or Cardiologist expert in Pulmonary Hypertension, a PTE surgeon, a BPA interventionalist, a dedicated radiologist, cardiothoracic anesthesia and Vascular Medicine or Hematology. Careful assessment of precise imaging and hemodynamic data is needed for operability assessment in the context of the experience of the CTEPH team and surgeon. Medical therapy and BPA are indicated for inoperable CTEPH and residual CTEPH after PTE. Increasingly, multimodality approaches, including surgery, BPA and medical therapy are utilized for best outcomes. SUMMARY: An expert CTEPH center requires a multidisciplinary team with dedicated specialists, and time to develop the experience and expertise to achieve high volumes and good outcomes.

Dual energy CT based scoring in chronic thromboembolic pulmonary hypertension and correlation with clinical and hemodynamic parameters: a retrospective cross-sectional study.

Background: We used a dual energy computed tomography (DECT) based scoring system in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and correlated it with functional and hemodynamic parameters. Methods: This was a retrospective study on 78 patients with CTEPH who underwent DECT. First, clot burden score was calculated by assigning a following score: pulmonary trunk-5, each main pulmonary artery-4, each lobar-3, each segmental-2, and subsegmental-1 per lobe; sum total was then calculated. Perfusion defect (PD) score was calculated by assigning 1 point to each segmental PD. Combined score was calculated by adding the clot burden and PD score. All three scores were correlated with clinical and hemodynamic parameters that included New York Heart Association (NYHA) functional class, 6-minute walk distance (6MWT) in feet, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), pulmonary arterial pressure (PAP) [systolic PAP (sPAP), diastolic PAP (dPAP) and mean PAP (mPAP)], pulmonary vascular resistance (PVR), right atrial pressure, cardiac output, and cardiac index. Results: Clot burden score, PD score, and combined score all positively correlated with sPAP (0.25, 0.34, 0.34), PVR (0.27, 0.30, 0.34), and mPAP (0.28, 0.31, 0.36). There was no statistically significant correlation of clot burden score, PD score and combined score with 6MWT, % predicted 6MWT, FEV1, FEV1%, FVC, FVC%, DLCO% and NYHA functional class. Conclusions: DECT based scoring in CTEPH is feasible and correlates positively with sPAP, mPAP and PVR. Combined score has the highest magnitude of correlation.

Assessment for residual disease after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.

Objectives: Pulmonary endarterectomy (PEA) is recommended for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH) and is potentially curative. However, persistent/recurrent CTEPH post-PEA can occur. Here we describe symptom and diagnostic assessment rates for residual disease post-PEA and longitudinal diagnostic patterns before and after riociguat approval for persistent/recurrent CTEPH after PEA. Methods: This US retrospective cohort study analysed MarketScan data (1 January 2002-30 September 2018) from patients who underwent PEA following a CTEPH/pulmonary hypertension (PH) claim with at least 730 days of continuous enrolment post-PEA. Data on pre-specified PH symptoms and the types and timings of diagnostic assessments were collected. Results: Of 103 patients (pre-riociguat approval, n=55; post-riociguat approval, n=48), residual PH symptoms >3 months after PEA were reported in 89% of patients. Overall, 89% of patients underwent one or more diagnostic tests (mean 4.6 tests/patient), most commonly echocardiography (84%), with only 5% of patients undergoing right heart catheterisation (RHC). In the post- versus pre-riociguat approval subgroup, assessments were more specific for CTEPH with an approximately two-fold increase in 6-min walk distance and N-terminal prohormone of brain natriuretic protein measurements and ventilation/perfusion scans, and a four-fold increase in RHCs. Conclusions: Low RHC rates suggest that many patients with PH symptoms post-PEA are not being referred for full diagnostic workup. Changes to longitudinal diagnostic patterns may indicate increased recognition of persistent/recurrent CTEPH post-PEA; however, there remains a need for greater awareness around the importance of continued follow-up for patients with residual PH symptoms post-PEA.

Mechanistic Insights into Tricuspid Regurgitation Secondary to Pulmonary Arterial Hypertension.

The simultaneous presence of pulmonary arterial hypertension (PAH) and secondary tricuspid regurgitation (STR) portends particularly poor outcomes. However, not all patients with PAH develop significant STR, and the mechanisms and clinical implications underlying this phenomenon remain unclear. We sought to describe the functional, anatomic, hemodynamic, and clinical characteristics of patients with PAH with and without STR. Patients diagnosed with PAH between 2007 and 2013 were included. STR, defined by absent primary tricuspid valve disease on transthoracic echocardiogram, was considered significant if ≥ moderate in severity. The characteristics of right-sided chambers and tricuspid valve annuli and leaflets were compared between patients with significant versus nonsignificant STR using a transthoracic echocardiogram, cardiac computed tomography, and right-sided cardiac catheterization. These features were then correlated with the composite outcome of all-cause mortality and PAH hospitalization. Of 88 included patients, 52 had significant STR. No baseline clinical differences, including atrial fibrillation, were observed. Patients with significant STR had worse right ventricular dysfunction (tricuspid annular planar systolic excursion = 1.5 vs 2.1 cm; p = 0.02) and increased right ventricular sphericity (sphericity index = 1.8 vs 2; p = 0.004), with similar annular dimensions/shape, lengths/angles of the mural and septal leaflets, and tenting height. After a median of 54 months, right atrial mean pressure was independently associated with the composite outcome on multivariable analysis (hazard ratio = 1.07, p = 0.02). In conclusion, anatomic and functional alterations in the right ventricle rather than the tricuspid valve are implicated in developing significant STR in PAH. Multimodality imaging provides mechanistic insight, and hemodynamic assessment may offer prognostic guidance in this population.

Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database.

BACKGROUND: Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) being two large subgroups. Claims database studies provide insights into the real-world treatment patterns and outcomes among these patients. However, claims data do not provide sufficient detail to assign the clinical subtype of PH required for identifying these patients. METHODS: A panel of PH clinical experts and researchers was convened to discuss methodologies to identify patients with Group 3 PH associated with COPD or ILD in retrospective claims databases. To inform the discussion, a literature review was conducted to identify claims-based studies of Group 3 PH associated with COPD or ILD published from 2010 through June 2020. RESULTS: Targeted title and abstract review identified 11 claims-based studies and two conference abstracts (eight based in the United States [US] and five conducted outside the US) that met search criteria. Based on insights from the panel and literature review, the following components were detailed across studies in the identification of Group 3 PH associated with COPD and ILD: (a) COPD or ILD identification, (b) PH identification, (c) defining the sequence between COPD/ILD and PH, and (d) other PH Group and Group 3 PH exclusions. CONCLUSION: This article provides recommended approaches and considerations for identifying and studying patients with Group 3 PH associated with COPD or ILD using administrative claims data that provide the foundation for future validation studies.

Off-Label Use and Inappropriate Dosing of Direct Oral Anticoagulants in Cardiopulmonary Disease.

Direct oral anticoagulants (DOACs) are increasingly used in clinical practice and have become essential in the management of atrial fibrillation and VTE. The enthusiasm for DOACs has fueled the off-label application of these agents in cardiopulmonary disease, and their use has often outpaced the evidence supporting their application. This article reviews the evidence and current off-label use of DOACs in various cardiopulmonary disease states.

Predictors of survival in portopulmonary hypertension: a 20-year experience.

BACKGROUND AND OBJECTIVES: Portopulmonary hypertension (PoPH) is a rare complication of portal hypertension associated with poor survival. Scarce data is available on predictors of survival in PoPH with conflicting results. We sought to characterize the outcomes and variables associated with survival in a large cohort of patients with PoPH in an American population of patients. STUDY DESIGN AND METHODS: We identified PoPH patients from the Cleveland Clinic Pulmonary Hypertension Registry between 1998 and 2019. We collected prespecified data, particularly focusing on hepatic and cardiopulmonary assessments and tested their effect on long-term survival. RESULTS: Eighty patients with PoPH with a mean ± SD age of 54 ± 10 years, (54% females) were included in the analysis. The median Model for End-Stage Liver Disease with sodium (MELD-Na) score was 13.0 (10.0-18.0) at PoPH diagnosis. World Health Association functional class III-IV was noted in 57%. Mean pulmonary arterial pressure was 47 ± 10 mmHg and pulmonary vascular resistance 6.0 ± 2.8 Woods units. A total of 63 (78.5%) patients were started on pulmonary arterial hypertension (PAH)-specific treatment during the first 6 months of diagnosis. Survival rates at 1-, 3- and 5-year were 77, 52 and 34%, respectively. Cardiopulmonary hemodynamics as well as PAH-specific treatment did not affect survival. In the multivariable model, MELD-Na, resting heart rate and the presence of hepatic encephalopathy were independent predictors of survival. CONCLUSION: PoPH patients have poor 5-year survival which is strongly associated to the severity of underlying liver disease and not to the hemodynamic severity of PoPH; therefore efforts should be focused in facilitating liver transplantation for these patients.

Liver abnormalities in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease with high mortality. In recent years, it has been recognized that PAH is a multi-organ system disease, involving the systemic circulation, kidneys, skeletal muscles, and the central nervous system, among others. Right heart failure produces congestive hepatopathy, a disease state that has direct consequences on liver biochemistry, histology, and systemic glucose and lipid metabolism. This article aims to summarize the consequences of congestive hepatopathy with an emphasis on liver biochemistry, histology, and PAH-targeted therapy. Furthermore, PAH-specific changes in glucose and lipid metabolism will be discussed.

The breath print represents a novel biomarker of malnutrition in pulmonary arterial hypertension: A proof of concept study.

BACKGROUND: The breath print is a quantitative measurement of molecules in exhaled breath and represents a new frontier for biomarker identification. It is unknown whether this state-of-the-art, noninvasive method can detect malnutrition. We hypothesize that individuals with malnutrition will present with a distinguishable breath print. METHODS: We conducted a retrospective chart review on patients with previously analyzed breath samples to identify malnutrition. Breath was analyzed by selected-ion flow-tube mass spectrometry. Registered dietitians conducted a retrospective chart review to collect malnutrition diagnoses and nutrition status indicators. Patients were categorized into one of four groups: pulmonary arterial hypertension (PAH), PAH with malnutrition (PAH-Mal), control, and control with malnutrition (Control-Mal), based on the malnutrition diagnosis present in the patient's chart. Principle component analysis was conducted to characterize the breath print. A logistic regression model with forward selection was used to detect the best breath predictor combination of malnutrition. RESULTS: A total of 74 patients met inclusion criteria (PAH: 52; PAH-Mal: 10; control: 10; Control-Mal: 2). Levels of 1-octene (PAH-Mal, 5.1 ± 1.2; PAH, 12.5 ± 11.2; P = 0.005) and ammonia (PAH-Mal, 14.6 ± 15.8; PAH, 56.2 ± 64.2; P = 0.013) were reduced in PAH-Mal compared with PAH. The combination of 1-octene (P = 0.010) and 3-methylhexane (P = 0.045) distinguished malnutrition in PAH (receiver operating characteristic area under the curve: 0.8549). CONCLUSIONS: This proof of concept study provides the first evidence that the breath print is altered in malnutrition. Larger prospective studies are needed to validate these results and establish whether breath analysis may be a useful tool to screen for malnutrition in the clinical setting.

Simultaneous Pulmonary Artery Pressure and Left Ventricle Stroke Volume Assessment Predicts Adverse Events in Patients With Pulmonary Embolism.

Background Certain echocardiographic parameters may serve as early predictors of adverse events in patients with hemodynamically compromising pulmonary embolism (PE). Methods and Results An observational analysis was conducted for patients with acute pulmonary embolism evaluated by a Pulmonary Embolism Response Team (PERT) between 2014 and 2020. The performance of clinical prediction algorithms including the Pulmonary Embolism Severity Index and Carl Bova score were compared using a ratio of right ventricle and left ventricle hemodynamics by dividing the pulmonary artery systolic pressure by the left ventricle stroke volume. The primary outcome of in-hospital mortality, cardiac arrest, and the need for advanced therapies was evaluated by univariate and multivariable analyses. Of the 343 patients meeting the inclusion criteria, 215 had complete data. Pulmonary artery systolic pressure/left ventricle stroke volume was a clear predictor of the primary end point (odds ratio [OR], 2.31; P=0.005), performing as well or better than the Pulmonary Embolism Severity Index (OR, 1.43; P=0.06) or the Bova score (OR, 1.28; P=0.01). Conclusions This study is the first study to demonstrate the utility of early pulmonary artery systolic pressure/left ventricle stroke volume in predicting adverse clinical events in patients with acute pulmonary embolism. Pulmonary artery systolic pressure/left ventricle stroke volume may be a surrogate marker of ventricular asynchrony in high-risk pulmonary embolism and should be prognostically evaluated.

Evaluation and management of patients with chronic thromboembolic pulmonary hypertension - consensus statement from the ISHLT.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part II: Cardiac, surgical, perioperative, operative, and post-operative challenges and management statements.

Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD.