Post Pulmonary Embolism Syndrome Research Articles

Not Just CTEPH: A Narrative Review on the Spectrum Approach to Postpulmonary Embolism Conditions.

Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the right ventricle dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of post-PE dyspnea, which has been reported in highly comorbid with lung and heart diseases, so that a "two-hit" hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and/or respiratory diseases. More than one-third of PE survivors develops PPES, with only a small fraction (3-4%) represented by CTEPH. A value of ≈3% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between post-PE dyspnea and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension and if it is a precursor of CTEPH. Further research is needed to improve the understanding and the management of CTEPD and post-PE dyspnea.

Post-pulmonary embolism syndrome, CTEPD, and CTEPH.

Post-pulmonary embolism syndrome, CTEPD, and CTEPH.

Post-pulmonary embolism syndrome: A reminder for clinicians.

Acute pulmonary embolism (APE) is one of the leading causes of cardiovascular emergencies and the third leading cause of death. Although efforts focus on treating the acute event, patients who survive APE may develop long-term sequelae. Research reveals that approximately half of patients who have suffered an APE do not regain their previous level of function and experience a reduction in their quality of life for several years after the episode. Acute pulmonary embolism can be classified according to the risk of short-term mortality, with most mortality and morbidity concentrated in high-risk and intermediate-risk cases. The first-line treatment for APE is systemic anticoagulation. However, identifying and more aggressively treating people with intermediate to high risk, who have a more favorable risk profile for reperfusion treatments, could reduce short-term mortality and mitigate post-pulmonary embolism syndrome (PPES). Post-pulmonary embolism syndrome refers to a variety of persistent symptoms and functional limitations that occur after an APE. The presence of persistent dyspnea, functional limitations, and/or decreased quality of life after an APE has been recently termed "PPES," although this entity encompasses different manifestations. The most severe cause of persistent dyspnea is chronic thromboembolic pulmonary hypertension, where increased pulmonary artery pressure is due to the fibrotic organization of unresolved APE. Post-PE Syndrome is not always systematically addressed in management guidelines, and its prevalence may be underestimated. More research is needed to fully understand its causes and risk factors. Interventions such as cardiopulmonary rehabilitation have been suggested to improve the quality of life of patients with PPES. A comprehensive, evidence-based approach is essential to effectively prevent and manage PPES and improve the long-term outcomes and well-being of affected patients.

Postpulmonary embolism syndrome: what should we focus on?

Postpulmonary embolism syndrome: what should we focus on?

Dyspnea and Post-Pulmonary Embolism Syndrome after a Mild COVID-19 Infection.

Dyspnea and Post-Pulmonary Embolism Syndrome after a Mild COVID-19 Infection.

Assessing long-term symptoms in patients with post-pulmonary embolism syndrome using patientreported outcome measures

People who survive an episode of pulmonary embolism have an increased risk of developing chronic complications despite curative anticoagulant treatment. The association of dyspnoea, low functional capacity, right heart failure, chronic thromboembolic pulmonary hypertension, or chronic thromboembolic pulmonary disease is part of the notion of post-pulmonary embolic syndrome (PPES). The symptoms can be limiting, substantially affecting the quality of life. To improve the overall health outcomes of patients with acute pulmonary embolism, adequate measures to diagnose it and strategies to prevent long-term outcomes of pulmonary embolism are essential.The objective of this study is to provide a definition of PPES and review the most recommended patient-reported outcome measures (PROMs) for assessing the functionality of these patients.We searched PubMed for papers from the last 5 years that contain the terms: postpulmonary embolism syndrome; symptoms; PROMs; score; quality of life; dyspnea. Repetitive publications were excluded. The data from the publications have been summarized in this descriptive overview.

Patient-Reported Outcomes in Venous Thromboembolism: A Systematic Review of the Literature, Current Challenges, and Ways Forward.

Venous thromboembolism (VTE) affects >1.2 million Americans annually. Although the clinical outcomes and economic burdens of VTE have been well described, the impact of VTE on patients' health status has yet to be summarized. This systematic review summarizes how patient-reported outcome measures (PROMs) have been used in VTE to date. PubMed/MEDLINE was queried for literature published through March 2023 using PROMs in a population of patients with VTE. Studies were excluded if the reference was an editorial, review, or case report, or if the study included patients with conditions other than VTE. Qualitative analyses were performed. After screening and exclusion, 136 references were identified; 5 described PROM development, 20 focused on PROM validation, and 111 used PROMs in outcomes research. The most used generic PROMs were the 36-item Short-Form Health Survey and EuroQol 5-dimensional questionnaire, and the most common disease-specific PROMs were the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms and the Pulmonary Embolism Quality of Life Questionnaire. PROMs were used to quantify the changes in health status after diagnosis, characterize the trajectory of subsequent improvement, and identify drivers of continued impairments in health status like postthrombotic syndrome and postpulmonary embolism syndrome. PROMs were also used to investigate the impact of novel treatment modalities on quality of life. This review demonstrates the many benefits of PROM use, including quantifying changes in health status with treatment, capturing patients' experiences with the treatment itself, and identifying complications of VTE. Incorporating PROMs into VTE care will be an essential component of evaluating the effectiveness of novel therapies and should lead to improved shared decision-making for patients with VTE.

Symptoms Suggestive of Postpulmonary Embolism Syndrome and Utilization of Diagnostic Testing.

Persistent symptoms of chest pain, dyspnea, fatigue, lightheadedness, and/or syncope more than 3 months after an acute pulmonary embolism (PE) are collectively classified as postpulmonary embolism syndrome (PPES). Although PPES is increasingly recognized as an important long-term sequel of acute PE, its contemporary incidence is unclear. Furthermore, the utilization of diagnostic testing for further phenotypic characterization of these patients is unknown. This study aimed to define the incidence of PPES and evaluate the utilization of diagnostic tests among a national cohort of patients with PE. Retrospective cohort study was performed using the national administrative database, Clinformatics DataMart Database (Optum Insight), and included adult patients (18 years or older) with no history of acute PE or pulmonary hypertension, diagnosed with acute PE between October 1, 2016, and December 31, 2018. With acute PE event as the exposure, the incidence of symptoms consistent with PPES and diagnostic test utilization among patients with PPES were evaluated. Of 21,297 incident patients with acute PE, 11,969 (56.2%) showed ≥1 symptom of PPES, which was new since their pre-PE baseline. New dyspnea was the most common and noted in 3268/15,203 (21.5%) patients, followed by new malaise or fatigue in 2894/15,643 (18.5%) patients. Among the 11,969 patients with PPES, 5128 (42.8%) received ≥1 diagnostic test, with 3242 (27%) receiving a computed tomography pulmonary angiogram, 2997 (25%) receiving an echocardiogram, and 325 (2.7%) received a ventilation-perfusion scan within 3-12 months after PE. Significantly lower use of diagnostic testing was noted in patients older than 65 years (adjusted odds ratio, 0.89; 95% CI, 0.81-0.98). Symptoms consistent with PPES are common after acute PE, occurring in more than half of the patients. Diagnostic imaging for further phenotypic characterization is used in less than half of such patients with PPES.

Chronic thromboembolic pulmonary hypertension and the post-pulmonary embolism (PE) syndrome.

Over a third of patients surviving acute pulmonary embolism (PE) will experience long-term cardiopulmonary limitations. Persistent thrombi, impaired gas exchange, and altered hemodynamics account for aspects of the postpulmonary embolism syndrome that spans mild functional limitations to debilitating chronic thromboembolic pulmonary hypertension (CTEPH), the most worrisome long-term consequence. Though pulmonary endarterectomy is potentially curative for the latter, less is understood surrounding chronic thromboembolic disease (CTED) and post-PE dyspnea. Advances in pulmonary vasodilator therapies and growing expertise in balloon pulmonary angioplasty provide options for a large group of patients ineligible for surgery, or those with persistent postoperative pulmonary hypertension. In this clinical review, we discuss epidemiology and pathophysiology as well as advances in diagnostics and therapeutics surrounding the spectrum of disease that may follow months after acute PE.

Post-pulmonary embolism syndrome: long-term complications of pulmonary embolism

Background: People who survive an episode of pulmonary embolism (PE) have an increased risk of developing chronic complications even despite curative anticoagulant treatment. The association of dyspnea, low functional capacity, right heart failure, chronic thromboembolic pulmonary hypertension or chronic thromboembolic pulmonary disease is part of the notion of post-pulmonary embolic syndrome (PPES). Due to the fact that this syndrome is still not clearly described and mainly underdiagnosed, a poor awareness of the disease by patients and physicians leads to delaying specific treatment with unlikely improvement of quality of life for these patients. Chronic thromboembolic pulmonary hypertension is the most severe complication, which, if not diagnosed and not treated in time, can lead to fatal consequences. To improve the overall health outcomes of patients with acute PE, adequate measures to diagnose it and strategies to prevent long-term outcomes of pulmonary embolism are essential. Conclusions: In this article, the data from the latest publications have been summarized to clarify the notion of PPES and its diagnostic algorithm.

VTE epidemiology and challenges for VTE prevention at the population level

Venous thromboembolism (VTE) is a frequent disease affecting more than 1 in 12 individuals during their lifetime. VTE is associated with a substantial disease burden due to long-term complications such as recurrence, the post-thrombotic syndrome, and the post-pulmonary embolism syndrome. Despite the knowledge of several risk factors and triggers, more than one third of the VTE events occur in the absence of an obvious provoking factor. In this narrative review, we summarize studies presenting time trends in incidence rates of VTE after year 2000 and discuss potential reasons for the incidence trends as well as challenges for VTE prevention at the population level. Studies from US, Europe and Asia indicate that the incidence rates of VTE have increased slightly during the last twenty years. Of note, this increase has persisted beyond the implementation of computed tomography pulmonary angiography (CTPA) into routine clinical practice. The persisting rates are likely attributed to the concomitant increase in major risk factors for VTE, such as obesity, major surgery, and cancer. Apparently, more widespread use of thromboprophylaxis to high-risk groups have not counteracted the rates noticeably, indicating that an approach to change the risk factor profile in the general population may be warranted. Obesity is recognized as the strongest causal lifestyle factor for VTE with a population attributable fraction of 10–30%. However, the mechanisms by which obesity increases the VTE risk are poorly understood. By integrating multi-omics and system biology approaches, future epidemiological studies should focus on identifying biological pathways that drive thrombogenesis to reveal disease mechanisms and potential targets for prevention.

Neurophysiological mechanisms of exertional dyspnea in post-pulmonary embolism syndrome.

Following pulmonary embolism (PE), a third of patients develop persistent dyspnea, which is commonly termed the post-PE syndrome. The neurophysiological underpinnings of exertional dyspnea in patients with post-PE syndrome without pulmonary hypertension (PH) are unclear. Thus, the current study determined if abnormally high inspiratory neural drive (IND) due, in part, to residual pulmonary gas-exchange abnormalities, was linked to heightened exertional dyspnea and exercise limitation, in such patients. Fourteen participants with post-PE syndrome (without resting PH) and 14 age-, sex-, and body mass index-matched healthy controls undertook pulmonary function testing and a symptom-limited cycle cardiopulmonary exercise test with measurements of IND (diaphragmatic electromyography), ventilatory requirements for CO2 (V̇e/V̇co2), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs. control) had a reduced resting transfer coefficient for carbon monoxide (KCO: 84 ± 15 vs. 104 ± 14%pred, P < 0.001) and peak oxygen uptake (V̇o2peak) (76 ± 14 vs. 124 ± 28%pred, P < 0.001). IND and V̇e/V̇co2 were higher in post-PE than controls at standardized submaximal work rates (P < 0.05). Dyspnea increased similarly in both groups as a function of increasing IND but was higher in post-PE at standardized submaximal work rates (P < 0.05). High IND was associated with low KCO (r = -0.484, P < 0.001), high V̇e/V̇co2 nadir (r = 0.453, P < 0.001), and low V̇o2peak (r = -0.523, P < 0.001). In patients with post-PE syndrome, exercise IND was higher than controls and was associated with greater dyspnea intensity. The heightened IND and dyspnea in post-PE, in turn, were strongly associated with low resting KCO and high exercise V̇e/V̇co2, which suggest important pulmonary gas-exchange abnormalities in this patient population.NEW & NOTEWORTHY This study is the first to show that increased exertional dyspnea in patients with post-pulmonary embolism (PE) syndrome, without overt pulmonary hypertension, was strongly associated with elevated inspiratory neural drive (IND) to the diaphragm during exercise, compared with healthy controls. The greater IND was associated with impairments in pulmonary gas exchange and significant deconditioning. Our results help to explain why many patients with post-PE syndrome report significant dyspnea at relatively low levels of physical activity.

Measuring Quality of Life after Venous Thromboembolism: Who, When, and How?

There is a growing body of evidence revealing that many patients with a history of venous thromboembolism (VTE) suffer from long-lasting sequelae such as post-thrombotic syndrome and post-pulmonary embolism syndrome. These two syndromes are detrimental to patients as they affect their quality of life (QOL). From this perspective, monitoring QOL may play a crucial role to improve quality care in VTE patients. Many studies have explored possible temporal relations between VTE episodes and decreased functional status and/or QOL. However, studies exploring the implementation of QOL and functional status questionnaires in clinical practice are scarce. In this context, we discuss possible perspectives synthetized from available literature regarding in whom, when, and how QOL could be measured in clinical practice.

Postpulmonary Embolism Follow-Up and Epidemiology of Chronic Thromboembolic Pulmonary Hypertension

The follow-up of patients with acute pulmonary embolism is an essential component of their comprehensive care. This manuscript will discuss the critical components involved in the outpatient follow-up of pulmonary embolism, including the development of post hospitalization follow-up clinics, assessment of functional capacity and residual right ventricular function, anticoagulation, recurrence risk of venous thromboembolism, and retrieval of inferior vena cava filters. In addition to these listed topics, the epidemiology of chronic thromboembolic pulmonary hypertension will be discussed, including the spectrum of postpulmonary embolism syndrome (PPES), risk factors for the development of chronic thromboembolic pulmonary hypertension, and the incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism.

Acceptability of Exercise in Urban Emergency Department Patients With Metabolic Syndrome, Including a Subset With Venous Thromboembolism.

Metabolic syndrome (MetS) afflicts more than one-third of US adults. In venous thromboembolism (VTE), MetS increases the risk of recurrence and severity of the post-pulmonary embolism syndrome, disproportionately affecting persons of color in urban settings. Exercise can positively modulate components of MetS. Our objective was to survey a sample of urban emergency department (ED) patients with MetS on their exercise habits and interest in increasing activity levels and to compare ± VTE patients. This survey study consisted of: (1) International Physical Activity Questionnaire, and (2) Likert scale gauging interest in increasing activity levels. Any adult ED patient with a composite MetS profile was included. We surveyed 247 patients with an average age of 59 years and 57% reported Black race. Only 9% met recommendations for vigorous exercise and 28% for moderate activity, with no significant difference in the 18% with prior VTE. Fifty-seven percent responded positively regarding motivation in increasing activity. This survey presents novel data supporting the need and feasibility of an interventional study examining exercise as an adjuvant therapy in patients with MetS and VTE.

Dyspnea after pulmonary embolism: a nation-wide population-based case-control study.

Dyspnea is common after a pulmonary embolism. Often, but not always, the dyspnea can be explained by pre-existing comorbidities, and only rarely by chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is probably the extreme manifestation of a far more common condition, called the post-pulmonary embolism syndrome. The purpose of this retrospective study was to investigate the prevalence and predictors of dyspnea among Swedish patients that survived a pulmonary embolism, compared to the general population. All Swedish patients diagnosed with an acute pulmonary embolism in 2005 (n = 5793) were identified via the Swedish National Patient Registry. Patients that lived until 2007 (n = 3510) were invited to participate. Of these, 2105 patients responded to a questionnaire about dyspnea and comorbidities. Data from the general population (n = 1905) were acquired from the multinational MONItoring of trends and determinants in CArdiovascular disease health survey, conducted in 2004. Patients with pulmonary embolism had substantially higher prevalences of both exertional dyspnea (53.0% vs. 17.3%, odds ratio (OR): 5.40, 95% confidence intervals (CI): 4.61–6.32) and wake-up dyspnea (12.0% vs. 1.7%, OR: 7.7, 95% CI: 5.28–11.23) compared to control subjects. These differences remained after adjustments and were most pronounced among younger patients. The increased risk for exertional dyspnea and wake-up dyspnea remained after propensity score matching (OR (95% CI): 4.11 (3.14–5.38) and 3.44 (1.95–6.06), respectively). This population-based, nation-wide study demonstrated that self-reported dyspnea was common among patients with previous pulmonary embolism. This finding suggested that a post-pulmonary embolism syndrome might be present, which merits further investigation.

Efficacy and safety of a 12-week outpatient pulmonary rehabilitation program in Post-PE Syndrome

BackgroundThe Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and deconditioning. ObjectivesTo assess underlying physiological determinants of PPES, and efficacy and safety of rehabilitation training in these patients. Methods56 consecutive PE patients with persistent dyspnea and/or functional limitations despite ≥3 months of anticoagulation underwent standardized diagnostic work-up including exercise testing as part of routine practice. All diagnostic (imaging and cardiopulmonary function) tests were interpreted by a core group of experienced clinicians. A subgroup of patients without CTEPH or other treatable conditions was referred for a 12-week personalized rehabilitation program, studying changes in physical condition and patient-reported outcome measures. ResultsPersistent vascular occlusions were observed in 21/56 patients (38%) and CTEPH was confirmed in ten (18%). Regarding those without CTEPH, impaired cardiopulmonary responses were evident in 18/39 patients with available CPET data (46%), unrelated to chronic thrombi. Rehabilitation was completed by 27 patients after excluding 29 (patients with CTEPH or treatable comorbidities, refusal, ineligibility, or training elsewhere). Training intensity, PE-specific quality of life (PEmb-QoL) and fatigue (CIS) improved with a median difference of 20 W (p = 0.001), 3.9 points (p < 0.001) and 16 points (p = 0.003), respectively. Functional status (Post-VTE Functional Status Scale) improved ≥1 grade in 18 (67%) patients, and declined in one (3.7%). ConclusionsOur findings suggest that abnormal cardiopulmonary responses to exercise are common in patients with PPES and are not limited to those with chronic thrombi. Offering pulmonary rehabilitation to patients not treated otherwise seems safe and promising.

Determinants and Management of the Post-Pulmonary Embolism Syndrome.

Acute pulmonary embolism (PE) is not only a serious and potentially life-threatening disease in the acute phase, in recent years it has become evident that it may also have a major impact on a patient's daily life in the long run. Persistent dyspnea and impaired functional status are common, occurring in up to 50% of PE survivors, and have been termed the post-PE syndrome (PPES). Chronic thromboembolic pulmonary hypertension is the most feared cause of post-PE dyspnea. When pulmonary hypertension is ruled out, cardiopulmonary exercise testing can play a central role in investigating the potential causes of persistent symptoms, including chronic thromboembolic pulmonary disease or other cardiopulmonary conditions. Alternatively, it is important to realize that post-PE cardiac impairment or post-PE functional limitations, including deconditioning, are present in a large proportion of patients. Health-related quality of life is strongly influenced by PPES, which emphasizes the importance of persistent limitations after an episode of acute PE. In this review, physiological determinants and the diagnostic management of persistent dyspnea after acute PE are elucidated.

Impact of higher detection rate of residual pulmonary thromboemboli one-year after acute pulmonary embolism: modified CT scan imaging method with modified CT obstruction index

Abstract Background Recently, post pulmonary embolism (PE) syndrome or chronic thromboembolic disease after acute PE, has been recognized as important long-term complications. Furthermore, patients may develop with chronic thromboembolic pulmonary hypertension. Purpose We aimed to evaluate the frequency of residual pulmonary thromboemboli after acute PE by using our “higher”-resolution CT scan imaging method to detect residual thromboemboli down to sub-segmental pulmonary arteries. Methods This study was a prospective multi-center observational study. We enrolled consecutive 34 patients with acute symptomatic PE whose informed consent was obtained, and followed up for one year. One year after the onset of acute PE, patients were referred to our hospital and multiple examination including CT scan, 6-minute walk test (6MWT), questionnaire of SF-36, echocardiography and laboratory testing were performed. Additionally, we have modified the CT obstruction index (CTOI) to quantitatively evaluate the thromboemboli down to sub-segmental pulmonary arteries. Results Mean age was 60.5±15.8 years, and 56% were male. No patient was categorized as low recurrent VTE risk which was caused by transient factors, one patient was associated with active cancer, and 12% had known thrombophilia. In 85% of the patients, this onset was the first obvious episode of PE. At diagnosis, elevated B-type natriuretic peptide (BNP) (≥100 pg/ml) or N-terminal (NT)-proBNP (≥500 pg/ml) was observed in 45% of the patients. Median tricuspid regurgitation peak gradient (TRPG) by echocardiography was 30.9 (19.3–50.1) mmHg. Among all, 35% of the patients received single-drug approach with DOACs. At discharge, all of the patients except two were treated with DOACs. One year after the onset, 21% of the patient were in NYHA II and others were in NYHA I. It was notable that pulmonary thromboemboli was detected by our CT scan in 76% of the patients. Modified CTOI was median 11.9 (1.8–24.4) % as shown in the figure. In multiple regression analysis, TRPG at diagnosis and BNP at one month were significantly associated with mCTOI (β=0.536, p=0.002 and β=−0.482, p=0.003, respectively). Additionally, lowest SpO2 during 6MWT after one year from the onset, tended to inversely associate with mCTOI (β=−0.341, p=0.052). Conclusions Using our modified CT scan imaging method and modified CTOI, residual pulmonary thromboemboli was able to be detected more frequently than the previous studies. Residual pulmonary thromboemboli could be one of the cause of the post PE syndrome and lead to exercise-induced desaturation. Figures Funding Acknowledgement Type of funding source: None

Clinical and imaging outcomes after intermediate- or high-risk pulmonary embolus.

Long-term outcomes after acute pulmonary embolism vary from complete resolution to chronic thromboembolic pulmonary hypertension (CTEPH). Guidelines after acute pulmonary embolism are generally limited to anticoagulation duration. We assessed patients with estimated prognosis >1 year in our pulmonary hypertension clinic 2–4 months after treatment for intermediate- or high-risk acute pulmonary embolism. At follow-up, ventilation–perfusion scan and echocardiogram were offered. The aim of this study was to assess for recurrent symptomatic disease, residual imaging defects or right ventricular dysfunction, and functional disability after acute management of pulmonary embolism. After treatment for acute intermediate- or high-risk pulmonary embolism, 104 patients followed up in pulmonary hypertension clinic. Of those, 55% of patients had self-reported limitation in activity. No patients had symptomatic recurrence of pulmonary embolism. Forty-eight percent of patients had residual perfusion defects on perfusion imaging, while 91% of patients had either normal or only mildly enlarged right ventricles. We identified heart failure preserved ejection fraction, iron deficiency, and obstructive sleep apnea as significant contributors to breathlessness. Treatment of these conditions was associated with improvement. Surprisingly, we diagnosed CTEPH in nine patients; for some, chronic thrombus may already have been present at the time of index evaluation. Our findings suggest that follow-up in a dedicated pulmonary hypertension clinic 2–4 months after acute intermediate- or high-risk pulmonary embolism may add value to patient care. We identified treatable comorbidities that could be contributing to post-pulmonary embolism syndrome as well as CTEPH.