Balloon Pulmonary Angioplasty for the Treatment of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension is a rare form of pulmonary hypertension in patients who have evidence of chronic thromboembolic occlusion of the pulmonary vasculature. Historically, surgical pulmonary thromboendarterectomy has been the treatment of choice. However, with up to 40% of patients deemed inoperable, balloon pulmonary angioplasty has emerged as an additional treatment strategy. Balloon pulmonary angioplasty is a complementary strategy alongside surgical pulmonary thromboendarterectomy and offers the opportunity for pulmonary revascularization in patients who have more distal disease, higher comorbidities, or residual obstruction following operative intervention. This review examines the history of balloon pulmonary angioplasty, highlights its effectiveness, discusses important complications and risk reduction strategies, and emphasizes the importance of centers forming a multidisciplinary team of providers to manage the complexity of patients with chronic thromboembolic pulmonary hypertension.

From Trendelenburg to PERTs: Evolution in the Management of Massive Pulmonary Embolism.

Massive pulmonary embolism (MPE) is a serious condition affecting the pulmonary arteries and is difficult to diagnose, triage, and treat. The American College of Chest Physicians (AHA) and the European Society of Cardiology (ESC) have different classification approaches for PE, with the AHA defining three subtypes and the ESC four. Misdiagnosis is common, leading to delayed or inadequate treatment. The incidence of PE-related death rates has been increasing over the years, and mortality rates vary depending on the subtype of PE, with MPE having the highest mortality rate. The current definition of MPE originated from early surgical embolectomy cases and discussions among experts. However, this definition fails to capture patients at the point of maximal benefit because it is based on late findings of MPE. Pulmonary Embolism Response Teams (PERTs) have emerged as a fundamental shift in the management of MPE, with a focus on high-risk and MPE cases and a goal of rapidly connecting patients with appropriate therapies based on up-to-date evidence. This review highlights the challenges in diagnosing and managing MPE and emphasizes the importance of PERTs and risk stratification scores in improving outcomes for patients with PE.

Intervention Versus Medical Management of Pulmonary Embolism.

With a multitude of options for pulmonary embolism management, we review the most common diagnostic tools available for assessing risk as well as how each broad risk category is typically treated. Right heart dysfunction is the cornerstone for triage of these patients and should be the focus for decision-making, especially in challenging patients. We aim to provide a modern, clinical perspective for PE management in light of the multitude of intervention options.

Pulmonary Embolism Triage: When to Do What.

Anticoagulation has been the standard therapy for treating pulmonary embolism. However, newly developed pharmacological and interventional treatment options have been shown to provide benefit for certain patient populations, depending on how they present. This column highlights the use of massive pulmonary embolism risk stratification in determining the presence of cor pulmonale and offers several key points to remember when caring for patients with a pulmonary embolism.

Atrial Arrhythmias Following Pulmonary Thromboendarterectomy: A Comprehensive Review Of Current Literature.

Chronic thromboembolic pulmonary hypertension (CTEPH) presents as a progressive vascular condition arising from previous episodes of acute pulmonary embolism, contributing to the development of pulmonary hypertension (PH). Pulmonary thromboendarterectomy (PTE) is the gold-standard surgical treatment for CTEPH; however, it may be associated with postoperative sequelae, including atrial arrhythmias (AAs). This comprehensive literature review explores the potential mechanisms for PTE-induced AAs with emphasis on the role of PH-related atrial remodelling and the predisposing factors. The identified preoperative predictors for AAs include advanced age, male gender, elevated resting heart rate, previous AAs, and baseline elevated right atrial pressure. Furthermore, we explore the available data on the association between post-PTE pericardial effusions and the development of AAs. Lastly, we briefly discuss the emerging role of radiomic analysis of epicardial adipose tissue as an imaging biomarker for predicting AAs.

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study.

BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

Percutaneous mechanical thrombectomy in acute pulmonary embolism: Outcomes from a safety-net hospital.

BACKGROUND: Our study aims to present clinical outcomes of mechanical thrombectomy (MT) in a safety-net hospital. METHODS: This is a retrospective study of intermediate or high-risk pulmonary embolism (PE) patients who underwent MT between October 2020 and May 2023. The primary outcome was 30-day mortality. RESULTS: Among 61 patients (mean age 57.6 years, 47% women, 57% Black) analyzed, 12 (19.7%) were classified as high-risk PE, and 49 (80.3%) were intermediate-risk PE. Of these patients, 62.3% had Medicaid or were uninsured, 50.8% lived in a high poverty zip code. The prevalence of normotensive shock in intermediate-risk PE patients was 62%. Immediate hemodynamic improvements included 7.4 mmHg mean drop in mean pulmonary artery pressure (-21.7%, p < 0.001) and 93% had normalization of their cardiac index postprocedure. Thirty-day mortality for the entire cohort was 5% (3 patients) and 0% when restricted to the intermediate-risk group. All 3 patients who died at 30 days presented with cardiac arrest. There were no differences in short-term mortality based on race, insurance type, citizenship status, or socioeconomic status. All-cause mortality at most recent follow up was 13.1% (mean follow up time of 13.4 ± 8.5 months). CONCLUSION: We extend the findings from prior studies that MT demonstrates a favorable safety profile with immediate improvement in hemodynamics and a low 30-day mortality in patients with acute PE, holding true even with relatively higher risk and more vulnerable population within a safety-net hospital.

Low left ventricular outflow tract velocity time integral predicts normotensive shock in patients with acute pulmonary embolism.

In this study, we found that a low LVOT VTI (<15 cm), a simple bedside point-of-care measurement, predicts normotensive shock in patients with acute intermediate-risk PE.

The Initial Experience of Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension in Latvia.

Background: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent pulmonary hypertension after pulmonary endarterectomy (PEA) include targeted medical therapy and balloon pulmonary angioplasty (BPA). BPA is an emerging treatment modality that has been reported to improve functional capacity, pulmonary hemodynamics, and right ventricular function. Reports from expert centers are promising, but more data are needed to make the results more generalizable. Materials and Methods: We conducted a prospective analysis of nine consecutive CTEPH patients who underwent balloon pulmonary angioplasty (BPA) sessions at Pauls Stradins Clinical University Hospital in Riga, Latvia between 1 April 2022 and 1 July 2023. We assessed World Health Organization (WHO) functional class, 6 min walk distance (6MWD), blood oxygen saturation (SpO2), brain natriuretic peptide (BNP) level at baseline and 3 months after the first BPA session. For two patients on whom repeated BPA sessions were performed, we additionally assessed cardiac output (CO), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (mPAP). Results: A total of 12 BPA procedures for nine patients were performed; repeated BPA sessions were performed for two patients. Our results show a reduction in BNP levels and improvement in WHO functional class, 6MWD, and SpO2 after the first BPA session. Improvement in 6MWD was statistically significant. Additionally, an improvement in pulmonary hemodynamic parameters was observed. Conclusions: Our data show that BPA is an effective interventional treatment modality, improving both the pulmonary hemodynamics and functional status. Moreover, BPA is safe and excellently tolerated.

The Usefulness of the TAPSE/sPAP Ratio for Predicting Survival in Medically Treated Chronic Thromboembolic Pulmonary Hypertension.

OBJECTIVE: The ventriculoarterial uncoupling has been linked with unfavorable results as measured noninvasively by tricuspid annular plane systolic excursion divided by systolic pulmonary artery pressure (TAPSE/sPAP). However, its prognostic importance in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. Thus, we determine the effect of the TAPSE/sPAP ratio on outcomes and predictors of all-cause mortality in these patients. METHODS: We analyzed 56 subjects with medically treated CTEPH. Two-dimensional echocardiographic examination and right heart catheterization findings were recorded from the hospital database. Baseline New York Heart Association functional class (NYHA-FC), 6-min walk distance (6MWD), and brain natriuretic peptide (BNP) test results were recorded. RESULTS: The median age was 65.5 years. Over a median follow-up time of 27 months, 29 (51.8%) patients died. BNP values were higher (P = 0.008), 6MWD values were lower (P = 0.004), and NHYA-FC (P = 0.0001) was worse in the non-survivor group. TAPSE (P = 0.0001) and TAPSE/sPAP ratio (P = 0.001) were significantly lower and pulmonary vascular resistance (PVR) was higher in the non-survivor group (P = 0.03). The best cut-off value for the TAPSE/sPAP ratio for predicting mortality was 0.20 mm/mmHg and the survival rates were significantly lower in the TAPSE/sPAP ratio ≤0.20 group (log-rank P = 0.012). 6MWD (P = 0.005), NHYA-FC III-IV (P = 0.0001), TAPSE/sPAP ratio ≤0.20 (P = 0.017), PVR (P = 0.008), and TAPSE/sPAP ratio ≤0.20 combined with NYHA-FC III-IV (P = 0.0001) were significant determinants and TAPSE/sPAP ratio ≤0.20 combined with NYHA-FC III-IV was the only independent predictor of mortality (P = 0.003). CONCLUSION: Medically treated CTEPH patients with a TAPSE/sPAP ratio ≤0.20 had lower survival rates. TAPSE/sPAP ratio≤0.20 combined with NYHA-FC III-IV was the independent predictor of poor prognosis.

Changes in Lung Perfusion in Patients Treated with Percutaneous Mechanical Thrombectomy for Intermediate-Risk Pulmonary Embolism.

BACKGROUND: Current pulmonary embolism treatment options rely heavily on anatomical clot location. However, anatomical location does not necessarily determine adverse outcomes; rather, clinical severity is secondary to the degree of perfusion impairment. Dual-energy computed tomography pulmonary angiogram (DE-CTPA) can map perfusion at the time of pulmonary embolism diagnosis. Single-photon emission computed tomography ventilation-perfusion scans allow for perfusion tracking similar to DE-CTPA. METHODS: We present 3 patients with intermediate-risk pulmonary embolism treated with mechanical thrombectomy using the Inari FlowTriever System (Inari Medical, Irvine, Calif). Lung perfusion scoring was applied to pre-procedure and post-procedure imaging. We graded perfusion of each lobe in 3 planes. If the entire lobe was perfused, a score of 3 was assigned. If lung perfusion is normal, total perfusion score is 15. All patients had pre-procedure and follow-up transthoracic echocardiograms. RESULTS: All 3 patients were diagnosed with pulmonary embolism via DE-CTPA that showed right ventricle strain and had deep venous thrombosis. Following mechanical thrombectomy, patients immediately experienced improvement in perfusion score; scores continued to improve at follow-up. All patients also had improvement in right ventricle size or function on follow-up echocardiogram. DISCUSSION: Intermediate-risk pulmonary embolism often has large initial clot burden that predicts residual pulmonary vascular obstruction. Residual pulmonary vascular obstruction is associated with increased risk of death, recurrent thrombus, and chronic thromboembolic pulmonary hypertension. Clot removal via thrombectomy may decrease the prevalence of residual pulmonary vascular obstruction by improving lung perfusion. We found that mechanical thrombectomy increased lung perfusion immediately and at follow-up assessments.

Home Treatment Compared to Initial Hospitalization in Normotensive Patients with Acute Pulmonary Embolism in the Netherlands: A Cost Analysis.

BACKGROUND: Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking. AIM: The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized. METHODS: Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital. RESULTS: Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home (n = 181) and 4.3 days for those initially treated in hospital (n = 202). Total average costs per hospitalized patient were €3,209 and €1,512 per patient treated at home. The adjusted mean difference was €1,483 (95% confidence interval: €1,181-1,784). CONCLUSION: Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of €1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients.

Development and Validation of a Nomogram for Predicting the Long-Term Survival in Patients With Chronic Thromboembolic Pulmonary Hypertension.

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

Exercise hyperventilation and pulmonary gas exchange in chronic thromboembolic pulmonary hypertension: Effects of balloon pulmonary angioplasty.

BACKGROUND: Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. METHODS: In this longitudinal observational study, symptom-limited cardiopulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. RESULTS: Peak work rate improved by 20% after BPA whilst V̇E at peak did not change despite improved ventilatory efficiency (lower V̇E with respect to CO2 output [V̇CO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), V̇E and alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. CONCLUSIONS: Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

A Comparison of GFR Calculated by Cockcroft-Gault vs. MDRD Formula in the Prognostic Assessment of Patients with Acute Pulmonary Embolism.

INTRODUCTION: Risk stratification is mandatory for optimal management of patients with acute pulmonary embolism (APE). Previous studies indicated that renal dysfunction predicts outcome and can improve risk assessment in APE. AIM: The aim of the study was a comparison of estimated glomerular filtration rate (eGFR) formulas, MDRD, and Cockcroft-Gault (CG), in the prognostic assessment of patients with APE. MATERIALS AND METHODS: Data from 2274 (1147 M/1127 F, median 71 years) hospitalised patients with APE prospectively included in a multicenter, observational, cohort study were analysed. A serum creatinine measurement as a routine laboratory parameter at the cooperating centers and eGFR calculation were performed on admission. Patients were followed for 180 days. The primary outcome was death from any cause within 30 days. RESULTS: The eGFR levels assessed by both, MDRD (eGFRMDRD) and CG formula (eGFRCG), were highest in patients with low-risk APE and lowest in high-risk APE. The eGFR (using both methods) was significantly lower in nonsurvivors compared to survivors. Using a threshold of <60 ml/min/1.73 m2, eGFRMDRD revealed the primary outcome with sensitivity 67%, specificity 52%, PPV 8%, and NPV 97%, while eGFRCG had a sensitivity 62%, specificity 62%, PPV 8.6%, and NPV 96%. The area under the ROC curve for eGFRCG tended to be higher than that for eGFRMDRD: 0.658 (95% CI: 0.608-0.709) vs. 0.631 (95% CI: 0.578-0.683), p = 0.12. A subanalysis of ROC curves in a population above 65 yrs showed a higher AUC for eGFRCG than based on MDRD. Kaplan-Meier analysis showed a worse long-term outcome in patients with impaired renal function. CONCLUSION: eGFRMDRD and eGFRCG assessed on admission significant short- and long-term mortality predictors in patients with APE. The eGFRCG seems to be a slightly better 30-day mortality predictor than eGFRMDRD in the elderly.

Diagnostic Accuracy of D-Dimers for Predicting Pulmonary Embolism in COVID-19-Patients.

IMPORTANCE: Proinflammatory and hypercoagulable states with marked elevation seen in D-Dimer levels have been accurately described in patients infected by the SARS- Cov2 even without pulmonary embolism (PE). OBJECTIVES: To compare D-dimers values in patients infected by the novel Coronavirus 2019 (COVID-19) with and without PE and to establish an optimal D-dimer cut-off to predict the occurrence of PE, which guides pulmonary computed tomography angiography (CTPA) indication. METHODS: We retrospectively enrolled all COVID-19-patients admitted between October first and November 22th, 2020, at the University Hospital Center of Mohammed VI, Oujda (Morocco), suspected to have PE and underwent a CTPA. Demographic characteristics and blood test results were compared between PE-positive and PE-negative. The receiver operating characteristics (ROC) curve was constructed to establish an optimal D-Dimer cut-off to predict the occurrence of PE. RESULTS: The study population consisted of 84 confirmed COVID-19-patients. The mean age was 64.93 years (SD 14.19). PE was diagnosed on CTPA in 31 (36.9%) patients. Clinical symptoms and in-hospital outcomes were similar in both groups except that more men had PE (p = .025). The median value of D-dimers in the group of patients with PE was significantly higher (14 680[IQR 33620-3450]ng/mL compared to the group of patients without PE 2980[IQR 6870-1600]ng/mL [P < .001]. A D-dimer at 2600 ng/mL was the optimal cut-off for predicting PE with a sensitivity of 90.3%, and AUC was .773[CI 95%, .667 -.876). CONCLUSION: A D-dimer cut-off value of 2600 ng/mL is a significant predictor of PE in COVID-19-patients with a sensitivity of 90.3%.

Vascular involvement in chronic thromboembolic pulmonary hypertension is associated with spirometry obstructive impairment.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension caused by persistent thromboembolism of the pulmonary arteries. In clinical practice, CTEPH patients often show obstructive ventilatory impairment, even in the absence of a smoking history. Recent reports imply a tendency for CTEPH patients to have a lower FEV1.0; however, the mechanism underlying obstructive impairment remains unknown. METHODS: We retrospectively analyzed CTEPH patients who underwent a pulmonary function test and respiratory impedance test to evaluate their exertional dyspnea during admission for right heart catheterization from January 2000 to December 2019. We excluded patients with a smoking history to rule out the effect of smoking on obstructive impairment. RESULTS: A total of 135 CTEPH patients were analyzed. The median FEV1.0/FVC was 76.0%, %FEV 1.0 had a negative correlation with the mean pulmonary artery pressure and pulmonary vascular resistance and the CT Angiogram (CTA) obstruction score. A multivariate regression analysis revealed that the CTA obstruction score was an independent factor of a lower %FEV1.0. In the 54 patients who underwent pulmonary endarterectomy, %FEV1.0 was improved in some cases and was not in some. Mean PAP largely decreased after PEA in the better %FEV1.0 improved cases, suggesting that vascular involvement in CTEPH could be associated with spirometry obstructive impairment. CONCLUSION: %FEV1.0 had a significant correlation with the CTA obstruction score. Obstructive impairment might have an etiological relationship with vascular involvement. Further investigations could shed new light on the etiology of CTEPH.

Comparison of Outcomes in Patients With COVID-19 and Thrombosis Versus Those Without Thrombosis.

The occurrence of venous thromboembolisms in patients with COVID-19 has been established. We sought to evaluate the clinical impact of thrombosis in patients with COVID-19 over the span of the pandemic to date. We analyzed patients with COVID-19 with a diagnosis of thrombosis who presented to the MedStar Health system (11 hospitals in Washington, District of Columbia, and Maryland) during the pandemic (March 1, 2020, to March 31, 2021). We compared the clinical course and outcomes based on the presence or absence of thrombosis and then, specifically, the presence of cardiac thrombosis. The cohort included 11,537 patients who were admitted for COVID-19. Of these patients, 1,248 had noncardiac thrombotic events and 1,009 had cardiac thrombosis (myocardial infarction) during their hospital admission. Of the noncardiac thrombotic events, 562 (45.0%) were pulmonary embolisms, 480 (38.5%) were deep venous thromboembolisms, and 347 (27.8%) were strokes. In the thrombosis arm, the mean age of the cohort was 64.5 ± 15.3 years, 53.3% were men, and the majority were African-American (64.9%). Patients with thrombosis tended to be older with more co-morbidities. The in-hospital mortality rate was significantly higher (16.0%) in patients with COVID-19 with concomitant non-cardiac thrombosis than in those without thrombosis (7.9%, p <0.001) but lower than in patients with COVID-19 with cardiac thrombosis (24.7%, p <0.001). In conclusion, patients with COVID-19 with thrombosis, especially cardiac thrombosis, are at higher risk for in-hospital mortality. However, this prognosis is not as grim as for patients with COVID-19 and cardiac thrombosis. Efforts should be focused on early recognition, evaluation, and intensifying antithrombotic management for these patients.