Exercise Pulmonary Hypertension in Heart Valve Disease.

The optimal management of heart valve disease (HVD) is still debated and many studies are underway to identify the best time to refer patients for the most appropriate treatment strategy (either conservative, surgical or transcatheter interventions). Exercise pulmonary hypertension (PH) can be detected during exercise stress echocardiography (ESE) and has been demonstrated to have an important prognostic role in HVD, by predicting symptoms and mortality. This review article aims to provide an overview on the prognostic role of exercise PH in valvulopathies, and its possible role in the diagnostic-therapeutic algorithm for the management of HVD.

Right heart failure in left heart disease: imaging, functional, and biochemical aspects of right ventricular dysfunction.

For decades, cardiologists have largely underestimated the role of the right heart in heart failure due to left heart disease. Nowadays, the importance of evaluating right ventricular (RV) structure and function in left heart failure is well documented and this concept has been emphasized in the most recent heart failure guidelines. However, several relevant questions remain unanswered such as the following: (a) which imaging technique (standard or 3D echocardiography or strain imaging or cardiac magnetic resonance) and, more, which parameters should be used to grade the severity of RV dysfunction? (b) do less widespread and less applied diagnostic tools such as cardiopulmonary stress testing and bioelectrical impedance analysis play a role in this field? (c) are there specific biochemical aspects of RV failure? (d) why notion of pathophysiology of heart and lung interaction are so well appreciated at an academic level but are not applied in the clinical setting? The present review has been prepared by the Heart Failure (HF) working group of the Italian Society of Cardiology and its main objective is to improve our understanding on RV dysfunction in heart failure.

Long-Term Safety, Outcome, and Clinical Effects of Subcutaneous and Intravenous Treprostinil Treatment in Patients with Severe Chronic Pulmonary Arterial Hypertension.

BACKGROUND: Current guidelines recommend treatment with parenteral prostacyclin analogs in patients with severe pulmonary arterial hypertension (PAH), who have insufficient response to treatment. Real-life data are sought to help physicians in treatment decisions and clinical care of patients. OBJECTIVE: This study analyzed safety, clinical effects, and long-term outcomes of subcutaneous (sc) and/or intravenous (iv) treprostinil via different pump systems in consecutive patients with PAH. METHODS: Thirty-seven patients with severe progressive PAH despite dual combination therapy (20 female, mean age: 52.3 ± 15 years, mean pulmonary vascular resistance: 12.1 ± 5.1 WU) were initiated with add-on treprostinil sc and were routinely clinically assessed. Changes in clinical parameters, adverse events, and outcome were analyzed retrospectively. RESULTS: In 24 of 37 patients, treprostinil administration was continued iv via implantation of LENUS Pro® pump after 3 ± 1.3 months, 6 patients continued with sc therapy, and 7 discontinued treatment. After 3, 6, 9, and 12 months of treprostinil treatment, patients showed a significant improvement in mean 6-min walk distance and tricuspid annular plane systolic excursion compared to baseline. In 8 of the 24 patients, iv pumps required surgical revision. During a mean follow-up of 2.82 ± 1.95 years, 12 patients died, four received lung transplantation. Transplant-free survival after 1, 2, and 3 years was 85.7%, 69.2%, and 65.3%, respectively. CONCLUSION: sc treprostinil as add-on to double combination treatment significantly improved exercise capacity and right heart function. In most patients, treprostinil could be continued via more tolerable iv administration approach (LENUS Pro® pump), showing reasonable overall survival with respect to the severity of PAH.

Impact of Hormonal-Anabolic Deficiencies in Idiopathic Pulmonary Arterial Hypertension.

Anabolic deficiencies play a pivotal role in left-sided heart failure. Little is known about their impact on idiopathic pulmonary arterial hypertension (iPAH). Therefore, the aim of this study was to assess the impact of multiple hormone-metabolic deficiencies on clinical features and outcomes in idiopathic pulmonary arterial hypertension. We have demonstrated that the assessment of anabolic hormone levels in patients with iPAH allows the identification of a subpopulation with worse exercise capacity, pulmonary hemodynamics, right ventricular size, and function generating the hypothesis about the potential role of hormonal replacement therapy. These data should be confirmed by larger studies.

Mildly Elevated Pulmonary Hypertension: Gray Zone or Already a Disease?

During the sixth World Symposium on Pulmonary Hypertension, the threshold of mean pulmonary arterial pressure (mPAP) for the definition of pulmonary hypertension (PH) has been lowered to a value of greater than 20 mmHg, measured by means of right heart catheterization at rest. In this review, we aim at describing the impact of the new definition of PH, analyzing the available data from the latest scientific literature concerning subjects with mPAP between 21 and 24 mmHg (defined as "mildly elevated PH"), discussing the impact of the new threshold for mPAP in the clinical practice, and highlighting the new perspectives in this field.

How to Treat Right Heart Failure. Tips for Clinicians in Everyday Practice.

In recent years, several observations reported that intolerance of physical exertion and other cardinal symptoms in heart failure (HF) are closely related to the functionality of the right ventricular (RV), regardless of left heart. It has been demonstrated that the RV dysfunction complicates the course, aggravates the quality of life, and increases the mortality of HF patients. The present review is aimed to report tips physicians about the current therapeutic management of right HF during acute stage and chronic phase, shedding light on the RV and its failure and providing physicians with essential information for everyday clinical practice.

[Targeted therapy for pulmonary arterial hypertension in patients without comorbidities]. / Gezielte medikamentöse Therapie der pulmonalarteriellen Hypertonie bei Patient*innen ohne Komorbiditäten.

The 2022 guidelines on pulmonary hypertension from the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) provide therapeutic strategies that account for the variability in the clinical presentation of newly diagnosed patients. We summarize treatment recommendations for pulmonary arterial hypertension (PAH) in patients without significant comorbidities, particularly for idiopathic, hereditary, drug/toxin-induced, or connective tissue disease-associated PAH. In this group of patients, multidimensional assessments for short-term mortality risk guide initial treatment decisions and treatment decisions during follow-up. Upfront dual combination therapy (phosphodiesterase type-5 inhibitor and endothelin receptor antagonist) is recommended for low- and intermediate-risk patients, and triple therapy including a parenteral prostacyclin should be considered in high- or intermediate-high-risk patients. If a low or intermediate-low-risk profile cannot be achieved during therapy, sequential add-on therapy escalation with parenteral prostacyclin or a prostacyclin receptor agonist should be considered, and switching from a phosphodiesterase type-5 inhibitor to a guanylate cyclase stimulator may also be considered.

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry.

BACKGROUND: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance-IR or diabetes mellitus-T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. METHODS: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. RESULTS: Compared with EU and IR, T2D was associated with increased filling pressures (E/e'ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, - 21% decline in TAPSE/PAPS ratio and - 20% decrease in peak VO2). CONCLUSION: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017.

Impairment of Inspiratory Muscle Function after COVID-19.

BACKGROUND: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting. METHODS: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021. RESULTS: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters. CONCLUSIONS: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results.

Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial.

AIMS: This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group. CONCLUSION: This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.

Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension.

BACKGROUND: Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients. METHODS: In this single-center, retrospective study we assessed indicators of iron status and clinical parameters specifying the time to clinical worsening (TTCW) and survival in PAH patients at time of initial diagnosis and at 1-year follow-up using univariable and multivariable analysis. RESULTS: In total, 150 patients were included with an invasively confirmed PAH and complete data on iron metabolism. The proportion of hypochromic erythrocytes > 2% at initial diagnosis was identified as an independent predictor for a shorter TTCW (p = 0.0001) and worse survival (p = 0.002) at initial diagnosis as well as worse survival (p = 0.016) at 1-year follow-up. Only a subset of these patients (64%) suffered from iron deficiency. Low ferritin or low serum iron neither correlated with TTCW nor survival. Severe hemoglobin deficiency at baseline was significantly associated with a shorter TTCW (p = 0.001). CONCLUSIONS: The presence of hypochromic erythrocytes > 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients. Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia. Further studies are needed to confirm the results and to investigate therapeutic implications.

Effect of Supervised Training Therapy on Pulmonary Arterial Compliance and Stroke Volume in Severe Pulmonary Arterial Hypertension and Inoperable or Persistent Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. OBJECTIVES: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). METHOD: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. RESULTS: Low-dose exercise training at 4-7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group -0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15-0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group -4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5-21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. CONCLUSIONS: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings.

Anabolic hormones and heart failure with preserved ejection fraction: looking for Ariadne's thread.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome that accounts for more than half of all heart failure patients. Identification, early diagnosis and management of patients are still complex, and no targeted treatment is available, since all tested drugs were not able to lower hard clinical outcomes. A multi-hormonal deficiency syndrome has been described in HFpEF patients suggesting that different hormones may represent new biomarkers of the disease, but their clinical utility is still debated. The natriuretic peptides are the cornerstone biomarker in heart failure, predicting cardiovascular death and heart failure hospitalization. Testosterone and DHEA-S deficiencies have been reported in HFpEF and associated with right ventricular impairment and diastolic dysfunction. IGFBP-1/IGF-1 axis correlates with echocardiographic parameters of HFpEF patients and with several prognostic biomarkers including NT-proBNP and C reactive protein. Low triiodothyronine syndrome is frequently found in HFpEF and thyroid hormones should represent a potential biomarker of risk stratification and prognosis.

Role of Cardiac Magnetic Resonance Imaging in Heart Failure.

This review describes the current role and potential future applications of cardiac magnetic resonance (CMR) for the management of heart failure (HF). CMR allows noninvasive morphologic and functional assessment, tissue characterization, blood flow, and perfusion evaluation. CMR overcomes echocardiography limitations (geometric assumptions, interobserver variability and poor acoustic window) and provides incremental information in relation to cause, prognosis, and treatment monitoring of patients with HF.

Exercise Intolerance in Heart Failure with Preserved Ejection Fraction.

Exercise intolerance represents a typical feature of heart failure with preserved ejection fraction (HFpEF), and is associated with a poor quality of life, frequent hospitalizations, and increased all-cause mortality. The cardiopulmonary exercise test is the best method to quantify exercise intolerance, and allows detection of the main mechanism responsible for the exercise limitation, influencing treatment and prognosis. Exercise training programs improve exercise tolerance in HFpEF. However, studies are needed to identify appropriate type and duration. This article discusses the pathophysiology of exercise limitation in HFpEF, describes methods of determining exercise tolerance class, and evaluates prognostic implications and potential therapeutic strategies.

Clinical Method Applied to Focused Ultrasound: The Case of Wells' Score and Echocardiography in the Emergency Department: A Systematic Review and a Meta-Analysis.

Background and Objectives: bedside cardiac ultrasound is a widely adopted method in Emergency Departments (ED) for extending physical examination and refining clinical diagnosis. However, in the setting of hemodynamically-stable pulmonary embolism, the diagnostic role of echocardiography is still the subject of debate. In light of its high specificity and low sensitivity, some authors suggest that echocardiographic signs of right ventricle overload could be used to rule-in pulmonary embolism. In this study, we aimed to clarify the diagnostic role of echocardiographic signs of right ventricle overload in the setting of hemodynamically-stable pulmonary embolism in the ED. Materials and Methods: we performed a systematic review of literature in PubMed, Web of Science and Cochrane databases, considering the echocardiographic signs for the diagnosis of pulmonary embolism in the ED. Studies considering unstable or shocked patients were excluded. Papers enrolling hemodynamically stable subjects were selected. We performed a diagnostic test accuracy meta-analysis for each sign, and then performed a critical evaluation according to pretest probability, assessed with Wells' score for pulmonary embolism. Results: 10 studies were finally included. We observed a good specificity and a low sensitivity of each echocardiographic sign of right ventricle overload. However, once stratified by the Wells' score, the post-test probability only increased among high-risk patients. Conclusions: signs of echocardiographic right ventricle overload should not be used to modify the clinical behavior in low- and intermediate- risk patients according to Wells' score classification. Among high-risk patients, however, echocardiographic signs could help a physician in detecting patients with the highest probability of pulmonary embolism, necessitating a confirmation by computed tomography with pulmonary angiography. However, a focused cardiac and thoracic ultrasound investigation is useful for the differential diagnosis of dyspnea and chest pain in the ED.

Risk stratification and prognostic factors in patients with pulmonary arterial hypertension and comorbidities a cross-sectional cohort study with survival follow-up.

BACKGROUND: The objective of this study was to analyze prognostic factors and risk stratification in patients with pulmonary arterial hypertension (PAH) and comorbidities. METHODS: Patients with invasively diagnosed PAH were included in the analysis. Comorbidities were clinically diagnosed as proposed in the 6th World Symposium of pulmonary hypertension. Uni- and multivariate analysis were employed for identification of factors predicting survival and time to first clinical worsening (TTCW). Risk stratification was based on parameters from ESC/ERS-guidelines 2015. RESULTS: In total 142 patients were enrolled in the study, 90 of them were diagnosed as PAH without and 52 with comorbidities. All patients received targeted PAH therapy and were followed for 3.3 ± 2.4 years. In PAH patients without comorbidities survival and TTCW were significantly associated with reduced 6-min walking distance (6MWD), elevated N-terminal pro brain natriuretic peptide (NT-proBNP), WHO-functional class (WHO-FC) and right atrial (RA) area. In the multivariate analysis, 6MWD was an independent predictor for survival (p = 0.002) and WHO-FC for TTCW (p = 0.001). In patients with PAH and comorbidities these parameters had no significant association with survival and TTCW. Average risk score was significantly associated with survival (p = 0.001) and TTCW (p = 0.013) in PAH but not in PAH with comorbidities (both p > 0.05; figure 1). CONCLUSION: Risk stratification based on ESC/ERS-guidelines could only be confirmed in patients without comorbidities, but not in patients with PAH and comorbidities. The data of this study suggest, that a different risk stratification needs to be applied to PAH patients with comorbidities. Further studies are needed to confirm these results. TRIAL REGISTRATION: Not applicable, retrospective registry.

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS.

AIM: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). METHODS: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio RESULTS: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01-0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988-0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. CONCLUSIONS: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

Myeloproliferative Diseases as Possible Risk Factor for Development of Chronic Thromboembolic Pulmonary Hypertension-A Genetic Study.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease which is often caused by recurrent emboli. These are also frequently found in patients with myeloproliferative diseases. While myeloproliferative diseases can be caused by gene defects, the genetic predisposition to CTEPH is largely unexplored. Therefore, the objective of this study was to analyse these genes and further genes involved in pulmonary hypertension in CTEPH patients. A systematic screening was conducted for pathogenic variants using a gene panel based on next generation sequencing. CTEPH was diagnosed according to current guidelines. In this study, out of 40 CTEPH patients 4 (10%) carried pathogenic variants. One patient had a nonsense variant (c.2071A>T p.Lys691*) in the BMPR2 gene and three further patients carried the same pathogenic variant (missense variant, c.1849G>T p.Val617Phe) in the Janus kinase 2 (JAK2) gene. The latter led to a myeloproliferative disease in each patient. The prevalence of this JAK2 variant was significantly higher than expected (p < 0.0001). CTEPH patients may have a genetic predisposition more often than previously thought. The predisposition for myeloproliferative diseases could be an additional risk factor for CTEPH development. Thus, clinical screening for myeloproliferative diseases and genetic testing may be considered also for CTEPH patients.

Pulmonary Embolism: A Practical Guide for the Busy Clinician.

Acute pulmonary embolism (PE) is the third most common acute cardiovascular condition, and its prevalence increases over time. D-dimer has a very high negative predictive value, and if normal levels of D-dimer are detected, the diagnosis of PE is very unlikely. The final diagnosis should be confirmed by computed tomographic scan. However, echocardiography is the most available, bedside, low-cost, diagnostic procedure for patients with PE. Risk stratification is of utmost importance and is mainly based on hemodynamic status of the patient. Patients with PE and hemodynamic stability require further risk assessment, based on clinical symptoms, imaging, and circulating biomarkers.