[Progress in the diagnose and treatment of pulmonary arterial thrombosis in situ].

In situ pulmonary arterial thrombosis (ISPAT) refers to the formation of new blood clots in the pulmonary arterial system in the absence of pre-existing clots in the peripheral venous system. With the emergence and prevalence of COVID-19, ISPAT has become an increasingly important cause of pulmonary arterial thrombosis (PAT) alongside thromboembolism. Several factors such as hypoxia, inflammation, endothelial dysfunction, and hypercoagulable state can lead to ISPAT, which is associated with a number of conditions such as thoracic trauma, partial lung resection, pulmonary infectious disease, pulmonary vasculitis, connective tissue diseases, severe pulmonary hypertension, radiation pneumonitis, and acute chest syndrome in sickle cell disease. It is important to differentiate between pulmonary thromboembolism (PTE) and ISPAT for proper disease management and prognosis. In this review, we summarized the characteristics of ISPAT under different disease conditions, the methods to distinguish ISPAT from PTE, and the best treatment strategies. We hoped that this review could improve clinicians' understanding of this independent disease and provide guidance for the refined treatment of patients with PAT.

[Consensus on the procedure of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension].

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group IV pulmonary hypertension, characterized by thrombotic occlusion of the pulmonary arteries leading to vascular stenosis or obstruction, progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and eventual right heart failure. Unlike other types of pulmonary hypertension, the prognosis of CTEPH can be significantly improved by surgery, vascular intervention, and/or targeted drug therapy. Pulmonary endarterectomy (PEA) is the preferred treatment of choice for CTEPH. However, PEA is an invasive procedure with high operative risks, and is currently only performed in a few centers in China. Balloon pulmonary angioplasty (BPA) is an emerging interventional technique for CTEPH, serving as an alternative for patients who are ineligible for PEA or with residual pulmonary hypertension after PEA. BPA is gaining traction in China, but its widespread adoption is limited due to its complexity, operator skills, and equipment requirements, a lack of standard operating procedures and technical guidance, which limit the further improvement and development of BPA in China. To address this, a multidisciplinary panel of experts was convened to develop the Consensus on the Procedure of Balloon Pulmonary Angioplasty for the Chronic Thromboembolic Pulmonary Hypertension, which fomulates guidelines on BPA procedural qualification, perioperative management, procedural planning, technical approach, and complication prevention, with the aim of providing recommendations and clinical guidance for BPA treatment in CTEPH and standardizing its clinical application in this setting. Summary of recommendations: Recommendation 1: It is recommended that physicians who specialize in pulmonary vascular diseases take the lead in formulating the diagnostic and treatment plans for CTEPH, using a multidisciplinary approach.Recommendation 2: Training in BPA technique is critical; novice operators should undergo standardized operative training with at least 50 procedures under the guidance of experienced physicians before embarking on independent BPA procedures.Recommendation 3: BPA requires catheterization labs, angiography systems, standard vascular interventional devices and consumables, drugs, and emergency equipment.Recommendation 4: Patient selection for BPA should consider cardiac and pulmonary function, coagulation status, and comorbid conditions to determine indications and contraindications, thereby optimizing the timing of the procedure and improving safety.Recommendation 5: In experienced centers, patients deemed likely to benefit from early BPA, based on clinical and imaging features of CTEPH and without elevated D-dimer levels, could bypass standard 3-month anticoagulation therapy.Recommendation 6: BPA is a complex interventional treatment that requires thorough pre-operative assessment and preparation.Recommendation 7: The use of perioperative anticoagulants in BPA requires a comprehensive risk assessment of intraoperative bleeding by the operator for individualized decision making.Recommendation 8: A variety of venous access routes are available for BPA; unless contraindicated, the right femoral vein is usually preferred because of its procedural convenience and reduced radiation exposure.Recommendation 9: For the different types of vascular lesion in CTEPH, treatment of ring-like stenoses, web-like lesions, and subtotal occlusions should be prioritized before addressing complete occlusions and tortuous lesions, in order to reduce complications and improve procedural safety.Recommendation 10: A targeted, incremental balloon dilatation strategy based on vascular lesions is recommended for BPA.Recommendation 11: Intravascular pulmonary artery imaging technologies, such as OCT and IVUS can assist in accurate vessel sizing and confirmation of wire placement in the true vascular lumen. Pressure wires can be used to objectively assess the efficacy of dilatation during BPA.Recommendation 12: Endpoints for BPA treatment should be individually assessed, taking into account improvements in clinical symptoms, hemodynamics, exercise tolerance, and quality of life.Recommendation 13: Post-BPA routine monitoring of vital signs is essential; anticoagulation therapy should be initiated promptly post-procedure in the absence of complications. In cases of intraoperative hemoptysis, postoperative anticoagulation regimen adjustments should be adjusted according to the bleeding severity.Recommendation 14: If reperfusion pulmonary edema occurs during or after BPA, ensure adequate oxygenation, diuresis, and consider non-invasive positive-pressure ventilation if necessary, while severe cases may require early mechanical ventilation assistance or ECMO.Recommendation 15: In cases of intraoperative hemoptysis, temporary balloon occlusion to stop bleeding is recommended, along with protamine to neutralize heparin. Persistent bleeding may warrant the use of gelatin sponges, coil embolization, or covered stent implantation.Recommendation 16: For contrast imaging during BPA, non-ionic, low or iso-osmolar contrast agents are recommended, with hydration status determined by the patient's clinical condition, cardiac and renal function, and intraoperative contrast volume used.

Efficacy and safety of catheter-based thrombectomy versus catheter-directed thrombolysis in acute pulmonary embolism.

Data comparing catheter-based thrombectomy (CBT) and catheter-directed thrombolysis (CDT) in acute pulmonary embolism are lacking. To address this, we performed a meta-analysis of prospective and retrospective studies of CBT and compared it to performance goal rates of mortality and major bleeding from a recently published network meta-analysis. When compared with performance goal for CDT based on historical studies, CBT was noninferior for all-cause mortality (6.0% vs 6.87%; P-valueNI < .001), non-inferior and superior for major bleeding (4.9% vs 11%; P-valueNI < .001 and P < .001 for superiority).

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.

Effects of right ventricular remodeling in chronic thromboembolic pulmonary hypertension on the outcomes of balloon pulmonary angioplasty: a 2D-speckle tracking echocardiography study.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

Percutaneous interventions for pulmonary embolism.

Pulmonary embolism (PE) ranks as a leading cause of in-hospital mortality and the third most common cause of cardiovascular death. The spectrum of PE manifestations varies widely, making it difficult to determine the best treatment approach for specific patients. Conventional treatment options include anticoagulation, thrombolysis, or surgery, but emerging percutaneous interventional procedures are being investigated for their potential benefits in heterogeneous PE populations. These novel interventional techniques encompass catheter-directed thrombolysis, mechanical thrombectomy, and hybrid approaches combining different mechanisms. Furthermore, inferior vena cava filters are also available as an option for PE prevention. Such interventions may offer faster improvements in right ventricular function, as well as in pulmonary and systemic haemodynamics, in individual patients. Moreover, percutaneous treatment may be a valid alternative to traditional therapies in high bleeding risk patients and could potentially reduce the burden of mortality related to major bleeds, such as that of haemorrhagic strokes. Nevertheless, the safety and efficacy of these techniques compared to conservative therapies have not been conclusively established. This review offers a comprehensive evaluation of the current evidence for percutaneous interventions in PE and provides guidance for selecting appropriate patients and treatments. It serves as a valuable resource for future researchers and clinicians seeking to advance this field. Additionally, we explore future perspectives, proposing "percutaneous primary pulmonary intervention" as a potential paradigm shift in the field.

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.

Aspiration of thrombus for intermediate-risk subacute pulmonary embolism.

Pulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543-603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543-603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.

[Extracorporeal Membrane Oxygenation Combined With Interventional Thrombectomy for Treating High-Risk Pulmonary Embolism Caused by Protein C Deficiency:Report of One Case].

Hereditary protein C deficiency is a chromosomal genetic disease caused by mutations in the protein C gene,which can lead to venous thrombosis and is mostly related to mutations in exons 4-9 and intron 8.Fatal pulmonary embolism caused by mutations in the protein C gene is rare,and the treatment faces great challenges.This article reports a case of fatal pulmonary embolism caused by a frameshift mutation in exon 8 of the protein C gene and summarizes the treatment experience of combining extracorporeal membrane oxygenation (for respiratory and circulatory support) with interventional thrombectomy,providing a basis for the diagnosis and treatment of this disease.

Current Topics from the Revised German S2k Guideline on Diagnosis and Treatment of Venous Thromboembolism.

It is an honor and a great pleasure for us to be guest editors for this special issue of Hämostaseologie - Progress in Haemostasis, which addresses important issues surrounding the complex of venous thromboembolism (VTE). In February 2023, the revised guideline on "Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism" has been published on the website of the Association of the Scientific Medical Societies in Germany (AWMF)1. This guideline was drawn up under the leadership of the German Society of Angiology (DGA), and representatives of 17 scientific societies contributed to its content. As an S2k guideline, its recommendations are consensus based and are the result of a systematic review and evaluation of current evidence and consideration of the benefits and harms of diagnostic and therapeutic options. In this special issue, guideline authors provide a comprehensive overview of selected guideline topics which might be of clinical relevance to our readers and our community of haemostaseologists.

Management of Deep Vein Thrombosis: An Update Based on the Revised AWMF S2k Guideline.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are the most common manifestations of venous thromboembolism (VTE). Most DVTs affect the lower-extremity veins. Since the symptoms of DVT are non-specific, a prompt and standardised diagnostic work-up is essential to minimise the risk of PE in the acute phase and to prevent thrombosis progression, post-thrombotic syndrome and VTE recurrence in the long-term. Only recently, the AWMF S2k guidelines on Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism have been revised. In the present article, we summarize current evidence and guideline recommendations focusing on lower-extremity DVT (LEDVT). Depending on whether the diagnostic work-up is performed by a specialist in vascular medicine or by a primary care physician, different diagnostic algorithms are presented that combine clinical probability, D-dimer testing and diagnostic imaging. The diagnosis of ipsilateral recurrent DVT poses a particular challenge and is presented in a separate algorithm. Anticoagulant therapy is an essential part of therapy, with current guidelines clearly favouring regimens based on direct oral anticoagulants over the traditional sequential therapy of parenteral anticoagulants and vitamin K antagonists. For most DVTs, a duration of therapeutic-dose anticoagulation of at least 3 to 6 months is considered sufficient, and this raises the question of the risk of VTE recurrence after discontinuation of anticoagulation and the need for secondary prophylaxis in the long-term. Depending on the circumstances and trigger factors that have contributed to the occurrence of DVT, management strategies are presented that allow decision-making taking into account the individual bleeding risk and patient's preferences.

Pulmonary Embolism: An Update Based on the Revised AWMF-S2k Guideline.

Pulmonary embolism (PE) is the third most common acute cardiovascular disease. The risk of PE increases with age and mortality is high. Patients are stratified into hemodynamically stable versus unstable patients, as this has important implications for diagnosis and therapy. Since clinical signs and symptoms of acute PE are nonspecific, the clinical likelihood of PE is estimated to guide diagnostic pathways. D-dimer testing is performed in hemodynamically stable patients with low or intermediate probability of PE and the visualization of thromboembolism and its sequelae is commonly achieved with computed tomography pulmonary angiography (CTPA), supplemented by ultrasound techniques. With confirmed PE, another risk stratification estimates disease severity and defines intensity and setting of the ensuing treatment. The therapeutic spectrum ranges from outpatient treatment with initial oral anticoagulation to thrombolytic or interventional treatment in the intensive care unit or catheterization laboratory. In single cases, even acute surgical thrombectomy is attempted.

Post-Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline.

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation-perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

Intensive Care Treatment of Pulmonary Embolism: An Update Based on the Revised AWMF S2k Guideline.

Acute pulmonary embolism (PE) remains a significant cause of morbidity and requires prompt diagnosis and management. The prognosis of affected patients depends on the clinical severity. Therefore, risk stratification is imperative for therapeutic decision-making. Patients with high-risk PE need intensive care. These include patients who have successfully survived resuscitation, with obstructive shock or persistent haemodynamic instability. Bedside diagnostics by means of sonographic procedures are of outstanding importance in this high-risk population. In addition to the treatment of hypoxaemia with noninvasive and invasive techniques, the focus is on drug-based haemodynamic stabilisation and usually requires the elimination or reduction of pulmonary vascular thrombotic obstruction by thrombolysis. In the event of a contraindication to thrombolysis or failure of thrombolysis, various catheter-based procedures for thrombus extraction and local thrombolysis are available today and represent an increasing alternative to surgical embolectomy. Mechanical circulatory support systems can bridge the gap between circulatory arrest or refractory shock and definitive stabilisation but are reserved for centres with the appropriate expertise. Therapeutic strategies for patients with intermediate- to high-risk PE in terms of reduced-dose thrombolytic therapy or catheter-based procedures need to be further evaluated in prospective clinical trials.

Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

Chronic Thromboembolic Pulmonary Hypertension.

This JAMA Insights discusses the symptoms, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension.