NT-pro-BNP is predictive of morbidity and mortality after pulmonary thromboendarterectomy and is independent of preoperative hemodynamics.

Current predictors of clinical outcomes after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are largely limited to preoperative clinical characteristics. N-terminal-pro-brain natriuretic peptide (NT-pro-BNP), a biomarker of right ventricular dysfunction, has not yet been well described as one such predictor. From 2017 to 2021, 816 patients with CTEPH referred to the University of California, San Diego for PTE were reviewed for differences in NT-pro-BNP to predict preoperative characteristics and postoperative outcomes up to 30 days post-PTE. For analysis, NT-pro-BNP was dichotomized to less than/equal to or greater than 1000 pg/mL based on the mean of the study population. Mean NT-pro-BNP was 1095.9 ±1783.4 pg/mL and median was 402.5 pg/mL (interquartile range: 119.5-1410.8). Of the 816 patients included, 250 had NT-pro-BNP > 1000 pg/mL. Those with NT-pro-BNP > 1000 pg/mL were significantly more likely to have worse preoperative functional class (III-IV) and worse preoperative hemodynamics. Patients with NT-pro-BNP > 1000 pg/mL also tended to have more postoperative complications including reperfusion pulmonary edema (22% vs. 5.1%, p < 0.001), airway hemorrhage (8.4% vs. 4.9%, p = 0.075), residual pulmonary hypertension (11.9% vs. 3.1%, p < 0.001), and 30-day mortality (4.8% vs. 1.1%, p = 0.001). Even after adjusting for confounders, patients with NT-pro-BNP > 1000 pg/mL had a 2.48 times higher odds (95% confidence interval: 1.45-4.00) of reaching a combined endpoint that included the above complications. Preoperative NT-pro-BNP > 1000 pg/mL is a strong predictor of more severe preoperative hemodynamics and identifies patients at higher risk for postoperative complications.

Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease.

BACKGROUND: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease. METHODS: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest. RESULTS: From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest. CONCLUSIONS: CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.

Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism.

RATIONALE: Chronic Thromboembolic Pulmonary Hypertension involves formation and non-resolution of thrombus, dysregulated inflammation, angiogenesis and the development of a small vessel vasculopathy. OBJECTIVES: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors. METHODS: We conducted a genome-wide association study on 1907 European cases and 10363 European controls. We co-analysed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism and idiopathic pulmonary arterial hypertension. MEASUREMENTS AND MAIN RESULTS: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our co-analysis we demonstrate further associations with chronic thromboembolic pulmonary hypertension at the F2, TSPAN15, SLC44A2 and F5 loci but find no statistically significant associations shared with idiopathic pulmonary arterial hypertension. CONCLUSIONS: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations to pulmonary embolism and to deep vein thrombosis.

Observational cohort study to validate SEARCH, a novel hierarchical algorithm to define long-term outcomes after pulmonary embolism.

BACKGROUND: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but are not defined and quantified sufficiently to serve as outcomes in clinical trials. The planned project will clinically validate a novel method to determine discrete, clinically meaningful diagnoses after acute PE. The method uses an algorithm entitled SEARCH, for symptom screen, exercise testing, arterial perfusion, resting echocardiography, confirmatory imaging and haemodynamic measurements. SEARCH is a stepwise algorithm that sorts patients by a hierarchical series of dichotomous tests into discreet categories of long-term outcomes after PE: asymptomatic, post-PE deconditioning, symptoms from other causes, chronic thromboembolism with ventilatory inefficiency, chronic thromboembolism with small stroke volume augmentation, chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. METHODS: The project will test the inter-rater reliability of the SEARCH algorithm by determining whether it will yield concordant post-PE diagnoses when six independent reviewers review the same diagnostic data on 150 patients evaluated at two time points after PE. The project will also determine whether the post-PE diagnoses are stable, according to the SEARCH algorithm, between the first evaluation and the subsequent one 6 months later. IMPLICATIONS: Validation of the SEARCH algorithm would offer clinicians a straightforward method to diagnose post-PE conditions that are rarely distinguished clinically. Their categorisation and definition will allow post-PE conditions to be used as endpoints in clinical trials of acute PE treatment. TRIAL REGISTRATION NUMBER: NCT05568927.

Updates in the diagnosis and management of chronic thromboembolic disease.

PURPOSE OF REVIEW: Chronic thromboembolic disease (CTED) is distinct from chronic thromboembolic pulmonary hypertension (CTEPH) and is defined by dyspnea on exertion after acute pulmonary embolism with the presence of residual perfusion defects and absence of resting pulmonary hypertension. Here, we review clinical features and diagnostic criteria for CTED and summarize treatment options. RECENT FINDINGS: The optimal management for CTED is unclear as the long-term outcomes of conservative vs. invasive treatment for this disease have not been reported. There are a few studies evaluating outcomes of pulmonary thromboendarterectomy and balloon pulmonary angioplasty (BPA) in CTED, concluding that these procedures are safe and effective in select patients. However, these trials are small nonrandomized observational studies, reporting outcomes only up to 1 year after the intervention. Conservative management of CTED with observation, pulmonary hypertension-targeted therapy, or cardiopulmonary rehabilitation has not been studied. It is unknown whether these treatments are as effective or superior to pulmonary thromboendarterectomy or BPA in CTED. SUMMARY: The management of CTED is individualized and based on symptoms and exercise limitations. Early referral of patients with CTED to a specialized CTEPH center is recommended to determine if watchful waiting, BPA, or pulmonary thromboendarterectomy is most beneficial.

Repeat pulmonary thromboendarterectomy outcomes: A 15-year single-center retrospective review.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is potentially curable via pulmonary thromboendarterectomy. A minority of patients experience recurrence of their symptoms and are eligible for repeat pulmonary thromboendarterectomy. However, little data exist regarding risk factors and outcomes for this patient population. METHODS: We performed a retrospective review of the University of California San Diego chronic thromboembolic pulmonary hypertension quality improvement database, including all patients who underwent pulmonary thromboendarterectomy from December 2005 to December 2020. Of the 2019 cases performed during this period, 46 were repeat pulmonary thromboendarterectomy procedures. Demographics, preoperative and postoperative hemodynamics, and surgical complications were compared between the repeat pulmonary thromboendarterectomy group and 1008 first pulmonary thromboendarterectomy group. RESULTS: Repeat pulmonary thromboendarterectomy recipients were more likely to be younger, to have an identified hypercoagulable state, and to have higher preoperative right atrial pressure. Etiologies of recurrent disease include incomplete initial endarterectomy, discontinuation of anticoagulation (noncompliance or for medical reasons), and anticoagulation treatment failure. Patients who received repeat pulmonary thromboendarterectomy had significant hemodynamic improvement, but less pronounced compared with patients who received first pulmonary thromboendarterectomy. Repeat pulmonary thromboendarterectomy was associated with an increased risk of postoperative bleeding, reperfusion lung injury, residual pulmonary hypertension, and increased ventilator, intensive care unit, and hospital days. However, hospital mortality was similar between the groups (2.2% vs 1.9%). CONCLUSIONS: This is the largest reported series of repeat pulmonary thromboendarterectomy surgery. Despite an increase in postoperative complications, this study demonstrates that repeat pulmonary thromboendarterectomy surgery can result in significant hemodynamic improvement with acceptable surgical mortality in an experienced center.

Distal vessel pulmonary thromboendarterectomy: Results from a single institution.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is primarily managed by pulmonary thromboendarterectomy (PTE). As advanced surgical techniques permit resection at the segmental and subsegmental level, PTE can now be curative for CTEPH mostly involving the distal pulmonary arteries. METHODS: Between January 2017 and June 2021, consecutive patients undergoing PTE were categorized according to the most proximal level of chronic thrombus resection: Level I (main pulmonary artery), Level II (lobar), Level III (segmental) and Level IV (subsegmental). Proximal disease patients (any Level I or II) were compared to distal disease (Level III or IV bilaterally) patients. Demographics, medical history, preoperative pulmonary hemodynamics, and immediate postoperative outcomes were obtained for each group. RESULTS: During the study period, 794 patients underwent PTE, 563 with proximal disease and 231 with distal disease. Patients with distal disease more frequently had a history of an indwelling intravenous device, splenectomy, upper extremity thrombosis or use thyroid replacement and less often had prior lower extremity thrombosis or hypercoagulable state. Despite more use of PAH-targeted medications in the distal disease group (63.2% vs 50.1%, p < 0.001), preoperative hemodynamics were similar. Both patient groups exhibited significant improvements in pulmonary hemodynamics postoperatively with comparable in-hospital mortality rates. Compared to proximal disease, a lower percentage of patients with distal disease showed residual pulmonary hypertension (3.1% vs 6.9%, p = 0.039) and airway hemorrhage (3.0% vs 6.6%, p = 0.047) postoperatively. CONCLUSIONS: Thromboendarterectomy for distal (segmental and subsegmental) CTEPH is technically feasible and may result in favorable pulmonary hemodynamic outcomes, without increased mortality or morbidity.

Multidisciplinary Approach to Chronic Thromboembolic Pulmonary Hypertension: Role of Radiologists.

Management of chronic thromboembolic pulmonary hypertension (CTEPH) should be determined by a multidisciplinary team, ideally at a specialized CTEPH referral center. Radiologists contribute to this multidisciplinary process by helping to confirm the diagnosis of CTEPH and delineating the extent of disease, both of which help determine a treatment decision. Preoperative assessment of CTEPH usually employs multiple imaging modalities, including ventilation-perfusion (V/Q) scanning, echocardiography, CT pulmonary angiography (CTPA), and right heart catheterization with pulmonary angiography. Accurate diagnosis or exclusion of CTEPH at imaging is imperative, as this remains the only form of pulmonary hypertension that is curative with surgery. Unfortunately, CTEPH is often misdiagnosed at CTPA, which can be due to technical factors, patient-related factors, radiologist-related factors, as well as a host of disease mimics including acute pulmonary embolism, in situ thrombus, vasculitis, pulmonary artery sarcoma, and fibrosing mediastinitis. Although V/Q scanning is thought to be substantially more sensitive for CTEPH compared with CTPA, this is likely due to lack of recognition of CTEPH findings rather than a modality limitation. Preoperative evaluation for pulmonary thromboendarterectomy (PTE) includes assessment of technical operability and surgical risk stratification. While the definitive therapy for CTEPH is PTE, other minimally invasive or noninvasive therapies also lead to clinical improvements including greater survival. Complications of PTE that can be identified at postoperative imaging include infection, reperfusion edema or injury, pulmonary hemorrhage, pericardial effusion or hemopericardium, and rethrombosis. ©RSNA, 2022 Online supplemental material is available for this article.

Airway Hemorrhage Complicating Pulmonary Thromboendarterectomy: Risk Factors and Outcomes.

BACKGROUND: Airway hemorrhage is a known complication of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension. Predisposing factors for postoperative airway hemorrhage have not been well described. The aims of this study were to determine the incidence and outcomes of airway hemorrhage after PTE and to identify potential risk factors. METHODS: This was a retrospective chart review of subjects undergoing PTE between 2015 and 2019. Postoperative airway hemorrhage was defined as significant endobronchial bleeding requiring withholding anticoagulation, bronchial blocker placement, and/or extracorporeal membrane oxygenation (ECMO). RESULTS: Of 877 subjects who underwent PTE, 58 subjects (6.6%) developed postoperative airway hemorrhage. Subjects with hemorrhage were more likely to be women (60% vs 45%, P = .03), to be older (57.8 vs 54.0 years, P = .04), and to have a higher incidence of preoperative hemoptysis (19.0% vs 7.6%, P = .006) compared with control subjects (subjects without airway hemorrhage). Those with hemorrhage had significantly higher preoperative right atrial pressure (P = .002) and pulmonary vascular resistance (P < .001) and a higher incidence of residual pulmonary hypertension (P = .005). Airway hemorrhage management included ECMO with bronchial blocker (n = 2), bronchial blocker without ECMO (n = 26), or withholding anticoagulation alone until bleeding subsided (n = 30). Mortality was significantly higher in those with airway hemorrhage compared with control subjects (13.8% vs 1.2%, P < .001). CONCLUSIONS: The incidence of postoperative airway hemorrhage is low but associated with significant mortality. Older age, female sex, preoperative hemoptysis, and worse preoperative pulmonary hypertension were associated with an increased risk of developing postoperative airway hemorrhage.

Evaluation of Dyspnea and Exercise Intolerance After Acute Pulmonary Embolism.

Long-term dyspnea and exercise intolerance are common clinical problems after acute pulmonary embolism. Unfortunately, no single test can distinguish among the range of potential pathologic outcomes after pulmonary embolism. We illustrate a stepwise approach to post-pulmonary embolism evaluation that uses a hierarchic series of clinically validated diagnostic tests. The algorithm is represented by the acronym SEARCH, which stands for Symptom screening, Exercise testing, Arterial perfusion, Resting echocardiography, Confirmatory chest imaging, and Hemodynamics measured by right heart catheterization. We illustrate the algorithm with a patient whom we saw in our pulmonary embolism follow-up clinic. Patients are asked at least 6 months after pulmonary embolism whether they have returned to their baseline level of respiratory comfort and exercise tolerance. Patients with dyspnea and exercise intolerance undergo noninvasive cardiopulmonary exercise testing to identify elevated ventilatory dead space ratios, decreased stroke volume augmentation with exercise, and other physiologic abnormalities during exertion. Ventilation-perfusion scanning is performed on those patients with exercise-related physiologic findings to confirm the presence of residual pulmonary arterial obstruction or to suggest alternative diagnoses. Resting echocardiography may provide evidence of pulmonary hypertension; confirmatory imaging with pulmonary angiography or CT angiography may disclose findings characteristic of chronic pulmonary artery obstruction. Finally, right heart catheterization is performed to confirm chronic thromboembolic pulmonary hypertension; if resting pulmonary hemodynamics are normal, then invasive cardiopulmonary exercise testing may disclose exercise-induced defects.

Direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension and the presence of recent thrombus during pulmonary endarterectomy.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulant therapy. The safety and efficacy of direct oral anticoagulant (DOAC) in the chronic and transitional management of CTEPH has not been investigated. We performed a retrospective analysis of 405 consecutive pulmonary endarterectomy (PEA) cases at the University of California, San Diego, from July 2015 through July 2017. PEA specimen was reviewed for the presence of acute or subacute thrombotic material distinct from the expected chronic disease removed at the time of PEA by two investigators blinded to the patient information. Of 405 PEA cases, 166 patients (41.0%) were anticoagulated with one of three available DOACs; 239 (59.0%) presented on either oral vitamin-K antagonist or chronic injectable therapy. There were no significant differences in baseline characteristics between DOAC and non-DOAC groups. Evidence of recent thrombus was observed in 22 (13.3%) in the DOAC group versus 16 (6.7%) within the non-DOAC group. The odds ratio of DOACs usage and evidence of recent thrombus was 2.34 (95% confidence interval: 1.1-5.0, p = 0.03) after adjusting for age, gender, race, body mass index, and history of antiphospholipid antibody syndrome. CTEPH patients referred for PEA while on DOAC therapy were twice as likely to have associated acute or subacute thrombi present at the time of surgery compared with those on more traditional, non-DOAC anticoagulant therapies. This raises questions of the safety and efficacy of DOACs in the chronic management of CTEPH.

Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension.

The management of pulmonary arterial hypertension (PAH) has become more complex in recent years because of increased pharmacotherapy options and longer patient survival with increasing numbers of comorbidities. As such, more opportunities exist for drug-drug interactions between PAH-targeted medications and medications potentially used to treat comorbid conditions. In this review, we provide an overview of pharmaceutical metabolism by cytochrome P450 and discuss important drug-drug interactions for the 14 Food and Drug Administration-approved medications for PAH in the nitric oxide (NO), endothelin, and prostacyclin pathways. Among the targets in the NO pathway (sildenafil, tadalafil, and riociguat), important interactions with nitrates, protease inhibitors, and other phosphodiesterase inhibitors can cause profound hypotension. In the endothelin pathway, bosentan is associated with more drug interactions via CYP3A4 inhibition; macitentan and ambrisentan have fewer interactions of note. Although the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.

Iron deficiency and pulmonary arterial hypertension.

The purpose of this review article is to provide a comprehensive review of iron deficiency in the setting of pulmonary arterial hypertension (PAH) and to evaluate the utility of iron supplementation in PAH. Iron deficiency is present in 33%-46% of patients with PAH and has been associated with reduced exercise capacity, compromised oxygen handling, deterioration of right ventricular function, and even mortality. Iron homeostasis and the pathophysiology of PAH are highly intertwined, which has inspired the use of iron supplementation in patients with iron deficiency and PAH. A literature search was performed to identify all available evidence on iron supplementation for PAH. Limited evidence has suggested poor oral bioavailability of oral iron dosed three times a day, but newer formulations such as ferrous maltol may provide better absorption and clinical benefit, especially when dosed less frequently, such as every other day. Intravenous (IV) iron has been shown in observational studies to improve outcomes, but the single randomized control trial in patients without anemia has failed to show benefits in any measure of exercise tolerance. Larger randomized control studies on oral iron with good bioavailability or IV iron in patients with anemia are warranted to explore the potential utility of iron supplementation in patients with PAH.

Outcomes of cardiopulmonary resuscitation in patients with pulmonary arterial hypertension.

Over the past 20 years, despite significant advancements in pulmonary arterial hypertension (PAH) medical therapy, many patients require admission to the hospital and are at risk for in-hospital cardiac arrest (IHCA). Prior data found poor survival in PAH patients after cardiac arrest. The purpose of this study was to explore post-IHCA outcomes in PAH patients receiving advanced medical therapies. This is a single-center retrospective study of PAH patients who underwent cardiopulmonary resuscitation for IHCA between July 2005 and May 2021. Patients were identified through an internal cardiac arrest database. Twenty six patients were included. Half of the cohort had idiopathic PAH, with 54% of patients on combination therapy, 27% on monotherapy, and 19% of patients on no therapy. Mean right atrial pressure, mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 13 ± 6 mmHg, 57 ± 13 mmHg, 2.0 ± 0.7 L/min/m2, and 14.5 ± 7.6 Wood units, respectively. Most common etiology of cardiac arrest was circulatory collapse. Initial arrest rhythm in all but one patient was pulseless electrical activity. Six patients (23%) achieved return of spontaneous circulation (ROSC) and one patient (4%) survived to hospital discharge. Rates of ROSC and survival to discharge after IHCA are poor in patients with PAH. Even patients with mild hemodynamics had low likelihood of survival. In patients who are lung transplant candidates, there should be early consideration of extracorporeal support before cardiac arrest.

Carfilzomib-associated pulmonary arterial hypertension in multiple myeloma.

Drug-induced pulmonary arterial hypertension (PAH) is constantly evolving as new drugs are developed. Carfilzomib is a recently approved therapy for relapsed and refractory multiple myeloma. While it has been associated with cardiovascular adverse events, such as ischemic heart disease and heart failure, PAH has not been a well-described side effect. We present two patients who developed PAH associated with initiation of carfilzomib. They both initially presented with severe dyspnea, had elevated right ventricular systolic pressure on transthoracic echocardiography and ultimately underwent right heart catheterization. With discontinuation of carfilzomib, both patients had improvement in hemodynamics. However, one patient required initiation of PAH-targeted therapies and has had worsening right ventricular function again despite permanent discontinuation of carfilzomib. It is important to recognize the association between carfilzomib and PAH. Echocardiography can be an important initial screening tool. PAH from carfilzomib therapy may be reversible, especially if diagnosed early; however, extended follow-up is essential.

Evolution of randomized, controlled studies of medical therapy in chronic thromboembolic pulmonary hypertension.

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty (BPA) and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since Aerosolized Iloprost Randomized (AIR), the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Study 1 (CHEST-1) study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multimodality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.

Management of Patients With Venous Thromboembolism After the Initial Treatment Period.

BACKGROUND: Venous thromboembolism (VTE) is a common medical problem seen in primary care settings. The most common long-term adverse sequelae are recurrent thromboembolism and incomplete resolution of the embolic material, which may result in pulmonary hypertension after pulmonary embolism and post-thrombotic changes in the leg after deep vein thrombosis. Although there are detailed guidelines for diagnosing and treating acute VTE, there are few focused articles that provide recommendations for primary care physicians (PCPs) about how to manage VTE patients after completion of the initial period of anticoagulation treatment. OBSERVATIONS: In this article, we highlight several important clinical decisions that must be addressed after the first 3 months of anticoagulation treatment is complete, with a focus on particular management issues for PCPs. CONCLUSIONS: The 2 most important decisions the PCP must make are to determine, first, if symptoms of acute VTE have indeed resolved, and second, if they have resolved, to assess the long-term risk of recurrent VTE versus the risk of potential bleeding and decide if anticoagulation should be stopped, or if indefinite anticoagulation treatment is indicated. Among higher-risk patients who may benefit from indefinite anticoagulation, the PCP should discuss both the risks and benefits of anticoagulation treatment, empowering the patient to actively participate in this important shared decision-making process.

Pulmonary Embolism Does Not Have an Unusually High Incidence Among Hospitalized COVID19 Patients.

INTRODUCTION: Acute respiratory illnesses from COVID19 infection are increasing globally. Reports from earlier in the pandemic suggested that patients hospitalized for COVID19 are at particularly high risk for pulmonary embolism (PE). To estimate the incidences of PE during hospitalization for COVID19, we performed a rigorous systematic review of published literature. METHODS: We searched for case series, cohort studies and clinical trials from December 1, 2019 to July 13, 2020 that reported the incidence of PE among consecutive patients who were hospitalized for COVID19 in ICUs and in non-ICU hospital wards. To reflect the general population of hospitalized COVID19 patients, we excluded studies in which subject enrollment was linked to the clinical suspicion for venous thromboembolism (VTE). RESULTS: Fifty-seven studies were included in the analysis. The combined random effects estimate of PE incidence among all hospitalized COVID19 patients was 7.1% (95% CI: 5.2%, 9.1%). Studies with larger sample sizes reported significantly lower PE incidences than smaller studies (r2 = 0.161, p = 0.036). The PE incidence among studies that included 400 or more patients was 3.0% (95% CI: 1.7%, 4.6%). Among COVID19 patients admitted to ICUs, the combined estimated PE incidence was 13.7% (95% CI: 8.0%, 20.6%). The incidence of ICU-related PE also decreased as the study sample sizes increased. The single largest COVID19 ICU study (n = 2215) disclosed a PE incidence of 2.3% (95% CI: 1.7%, 3.0%). CONCLUSION: PE incidences among hospitalized COVID19 patients are much lower than has been previously postulated based on smaller, often biased study reports. The incidence of "microthrombosis," leading to occlusion of microscopic blood vessels, remains unknown.

Pregnancy and pulmonary arterial hypertension: a case series and literature review.

BACKGROUND: Despite the development of advanced therapies for pulmonary arterial hypertension, pregnancy remains contraindicated in these patients owing to high maternal and fetal morbidity and mortality. Limited data exist regarding pregnancy management and outcome in this unique patient population. We describe a series of pregnant patients diagnosed as having pulmonary arterial hypertension before or during pregnancy who delivered at a tertiary center with a comprehensive and established pulmonary vascular disease program. OBJECTIVE: This study aimed to describe a single institution's experience and review the existing literature for pregnancy management and outcomes in patients with pulmonary arterial hypertension. STUDY DESIGN: A review of all patients with pulmonary arterial hypertension who were admitted for delivery between 2005 and 2019 at our institution was performed. All data were extracted from the electronic health record and included patient demographics, pulmonary arterial hypertension subtype, pulmonary arterial hypertension-targeted therapies, and mode of delivery and anesthesia. RESULTS: A total of 7 patients were identified; 5 patients had a prepartum diagnosis of pulmonary arterial hypertension, whereas 2 patients were diagnosed as having pulmonary arterial hypertension during the third trimester. All patients were started on prostacyclins and the majority were on combination pulmonary arterial hypertension-targeted therapy. The maternal mortality rate was 29%. Elective cesarean delivery was performed in more than 70% of cases, whereas 1 patient required an urgent cesarean delivery and 1 patient had a successful vaginal delivery. Most patients had epidural anesthesia. Notably, 2 patients required extracorporeal membrane oxygenation after delivery and both died. There were no cases of neonatal mortality. CONCLUSION: Our cases series and the published literature to date show that pregnancy in pulmonary arterial hypertension remains poorly tolerated despite marked advancements in pulmonary arterial hypertension-targeted therapies and postpartum care. A multidisciplinary team approach remains essential for the management of these patients.