Deisy Barrios

Risk stratification of patients with acute symptomatic pulmonary embolism

Patients with acute symptomatic pulmonary embolism (PE) who present with arterial hypotension or shock have a high risk of death (high-risk PE), and treatment guidelines recommend strong consideration of thrombolysis in this setting. For normotensive patients diagnosed with PE, risk stratification should aim to differentiate the group of patients deemed as having a low risk for early complications (all-cause mortality, recurrent venous thromboembolism, and major bleeding) (low-risk PE) from the group of patients at higher risk for PE-related complications (intermediate-high risk PE), so low-risk patients could undergo consideration of early outpatient treatment of PE and intermediate-high risk patients would undergo close observation and consideration of thrombolysis. Clinicians should also use risk stratification and eligibility criteria to identify a third group of patients that should not undergo escalated or home therapy (intermediate-low risk PE). Such patients should initiate standard therapy of PE while in the hospital. Clinical models [e.g., Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI)] may accurately identify those at low risk of dying shortly after the diagnosis of PE. For identification of intermediate-high risk patients with acute PE, studies have validated predictive models that use a combination of clinical, laboratory and imaging variables.

Continuation of low-molecular-weight heparin treatment for cancer related venous thromboembolism: a prospective cohort study in daily clinical practice

Essentials Low‐molecular‐weight heparin (LMWH) injections for venous thromboembolism (VTE) may be burdensome. Patients with active cancer and confirmed VTE were included to evaluate LMWH continuation. The cumulative incidence of discontinuation was 21% after a median period of 90 days. One out of five patients discontinued LMWH injections because of side effects.

Right heart thrombi in pulmonary embolism

There is a lack of comprehensive data on the prevalence, predictors and prognostic significance of right heart thrombi (RHT) in pulmonary embolism. In this study of patients with pulmonary embolism from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence and predictors of RHT, and the association between the presence of RHT and the outcomes of all-cause mortality, pulmonary embolism-related mortality, recurrences, and major bleeding through 30 days after initiation of pulmonary embolism treatment. Of 12 441 patients with pulmonary embolism and baseline echocardiographic data, 2.6% had RHT. The following increased the risk of RHT: younger age, previous bleeding, congestive heart failure, cancer, syncope, systolic blood pressure <100 mmHg, and arterial oxyhaemoglobin saturation <90%. Patients with RHT were significantly more likely to die from any cause (adjusted OR 2.50 (95% CI 1.62–3.84); p<0.001) and from pulmonary embolism (adjusted OR 4.29 (95% CI 2.45–7.48); p<0.001) during follow-up. RHT was associated with an increased risk of recurrence during follow-up (1.8% versus 0.7%; p=0.04). Major bleeding was similar in patients with and without RHT. In patients presenting with pulmonary embolism, RHT is relatively infrequent. Patients with RHT had a worse outcome when compared with those without RHT. Right heart thrombus is an independent predictor of death in patients with acute pulmonary embolism http://ow.ly/y5i5302CDCS

Assessment of right ventricular function in acute pulmonary embolism

Background The optimal approach to assess right ventricular (RV) function in patients with acute symptomatic pulmonary embolism (PE) lacks clarity. Methods This study aimed to evaluate the optimal approach to assess RV function in normotensive patients with acute symptomatic PE. Outcomes assessed through 30‐days after the diagnosis of PE included all‐cause mortality and complicated course. Results Eight hundred forty‐eight patients were enrolled. Multidetector computed tomography (MDCT) and transthoracic echocardiography agreed on the presence or absence of RV overload in 449 (53%) patients. The combination of the simplified Pulmonary Embolism Severity Index (sPESI) and MDCT showed a negative predictive value for 30‐day all‐cause mortality of 100%. Of the 43% that had an sPESI of >0 points and MDCT RV enlargement, 41 (11.3%) experienced a complicated course that included 24 (6.6%) deaths. One hundred twenty‐nine patients (15%) had an sPESI of >0 points, MDCT, and echocardiographic RV overload. Of these, 21 (16.3%) experienced a complicated course within the first 30 days, and 10 (7.7%) of them died. Conclusions Incorporation of echocardiographic RV overload to the sPESI and MDCT did not improve identification of low‐risk PE patients, whereas it improved identification of those at intermediate‐high risk for short‐term complications.

Risk Stratification for Proven Acute Pulmonary Embolism: What Information Is Needed?

Abstract Classification of risk drives treatment decisions for patients with acute symptomatic pulmonary embolism (PE). High‐risk patients with acute symptomatic PE have hemodynamic instability (i.e., shock or hypotension present), and treatment guidelines suggest systemically administered thrombolytic therapy in this setting. Normotensive PE patients at low risk for early complications (low‐risk PE) might benefit from treatment at home or early discharge, while normotensive patients with preserved systemic arterial pressure deemed as having a high risk for PE‐related adverse clinical events (intermediate‐high‐risk PE) might benefit from close observation and consideration of escalation of therapy. Prognostic tools (e.g., clinical prognostic scoring systems, imaging testing, and cardiac laboratory biomarkers) assist with the classification of patients into these categories.

Prognostic Significance of Right Heart Thrombi in Patients With Acute Symptomatic Pulmonary Embolism: Systematic Review and Meta-analysis

Background: For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity. Methods: We performed a meta‐analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography‐detectable RHT for the primary outcome of short‐term all‐cause mortality and the secondary outcome of short‐term PE‐related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms “right heart thrombi,” “pulmonary embolism,” and “prognos.*” A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity. Results: Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography‐detectable RHT died (16.7% [95% CI, 13.8–19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0–4.7]). RHT had a significant association with short‐term all‐cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I2 = 20%) and with PE‐related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0–11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7–13.6]; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I2 = 0%) studies. Conclusions: In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis. Trial Registry: PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/

Sex differences in the characteristics and short-term prognosis of patients presenting with acute symptomatic pulmonary embolism

Background We sought to examine sex-related differences in the characteristics and outcome in patients presenting with acute symptomatic pulmonary embolism (PE). Methods We conducted a retrospective cohort study of 2,096 patients diagnosed with acute PE. The characteristics were recorded at presentation. Treatment was at the discretion of patients’ physicians. The primary study outcome, all-cause mortality, and the secondary outcomes of PE-specific mortality, recurrent venous thromboembolism, and major bleeding were assessed during the first month of follow-up after PE diagnosis. Results Overall, the women were older than the men and had significantly higher rates of immobilization. They had significantly lower rates of chronic obstructive pulmonary disease and cancer. Women had a higher prevalence of syncope and elevated brain natriuretic peptide levels. Thirty-day all-cause mortality was similar between women and men (7.1% versus 6.2%; P = 0.38). Male gender was not independently significantly associated with PE-related death (adjusted odds ratio [OR] 1.02; 95% CI, 0.50 to 2.07; P = 0.96). Restricting the analyses to haemodynamically stable patients (n = 2,021), female gender was an independent predictor of all-cause (adjusted OR 1.56; 95% CI, 1.07 to 2.28; P = 0.02) and PE-specific mortality (adjusted OR 1.85; 95% CI, 1.02 to 3.33; P = 0.04). Compared with men, women were 2.05 times more likely to experience a major bleed. Conclusions Women and men with PE had different clinical characteristics, presentation, and outcomes. Women receiving anticoagulation have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Efficacy and safety outcomes of recanalisation procedures in patients with acute symptomatic pulmonary embolism: systematic review and network meta-analysis

Background We aimed to review the efficacy and safety of recanalisation procedures for the treatment of PE. Methods We searched PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through 31 July 2015 and included randomised clinical trials that compared the effect of a recanalisation procedure versus each other or anticoagulant therapy in patients diagnosed with PE. We used network meta-analysis and multivariate random-effects meta-regression to estimate pooled differences between each intervention and meta-regression to assess the association between trial characteristics and the reported effects of recanalisation procedures versus anticoagulation. Results For all-cause mortality, there were no significant differences in event rates between any of the recanalisation procedures and anticoagulant treatment (full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01; low-dose thrombolysis: 0.47; 95% CI 0.14 to 1.59; and catheter-associated thrombolysis: 0.31; 95% CI 0.01 to 7.96). Full-dose thrombolysis increased the risk of major bleeding (2.00; 95% CI 1.06 to 3.78) compared with anticoagulation. Catheter-directed thrombolysis was associated with the lowest probability of dying (surface under the cumulative ranking curve (SUCRA), 0.67), followed by low-dose thrombolysis (SUCRA, 0.66) and full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose thrombolysis was associated with the lowest probability of major bleeding (SUCRA, 0.61), followed by catheter-directed thrombolysis (SUCRA, 0.54) and full-dose thrombolysis (SUCRA, 0.17). The results were similar in sensitivity analyses based on restricting only to studies in haemodynamically stable patients with PE. Conclusions In the treatment of PE, recanalisation procedures do not seem to offer a clear advantage compared with standard anticoagulation. Low-dose thrombolysis was associated with the lowest probability of dying and bleeding. Trial registration number PROSPERO CRD42015024670.

Epidemiology, patterns of care and mortality for patients with hemodynamically unstable acute symptomatic pulmonary embolism

BACKGROUND Limited information exists about the epidemiology, management and outcomes of hemodynamically unstable patients with acute pulmonary embolism (PE). We aimed to evaluate the prevalence and outcomes of unstable PE, and to assess the acute management in routine clinical practice. METHODS This study included 34,380 patients from the RIETE registry with PE between 2001 and 2016. Primary outcomes included all-cause and PE-specific 30-day mortality. We used multivariable adjustments to calculate hazard ratios among unstable patients who did and did not receive reperfusion. RESULTS Overall, 1207 patients (3.5%) presented with hemodynamic instability. All-cause 30-day mortality was 14% and 5.4% in those with versus those without hemodynamic instability (P < 0.001). Two hundred and thirty eight (20%) unstable patients received reperfusion therapy. After multivariable adjustment, reperfusion therapy was associated with non-significantly reduced 30-day all-cause mortality (hazard ratio [HR] 0.71; 95% CI, 0.45 to 1.10; P = 0.12), and significantly reduced 30-day PE-related mortality (HR 0.56; 95% CI, 0.31 to 0.99; P = 0.04). When limiting the adjusted analyses to unstable patients with right ventricular dysfunction, the difference was significant for both all-cause (HR 0.65; 95% CI, 0.42 to 1.00; P = 0.05) and PE-related mortality (HR 0.52; 95% CI, 0.30 to 0.92; P = 0.02). CONCLUSIONS In a multinational registry of patients with PE, prevalence of hemodynamic instability was 3.5%, with high associated 30-day mortality rates. Although use of reperfusion was associated with lower mortality rates, particularly in patients with right ventricular dysfunction, it was used in only a fifth of patients.

Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study

BACKGROUND The inflammatory response associated with acute pulmonary embolism (PE) contributes to the development of right ventricular (RV) dysfunction. Nonsteroidal anti-inflammatory drugs (NSAIDs) may facilitate the reversal of PE-associated RV dysfunction. METHODS We randomly assigned normotensive patients who had acute PE associated with echocardiographic RV dysfunction and normal systemic blood pressure to receive intravenous (IV) diclofenac (two doses of 75mg in the first 24h after diagnosis) or IV placebo. All patients received standard anticoagulation with subcutaneous low-molecular-weight heparin (LMWH) and an oral vitamin K antagonist. RV dysfunction was defined by the presence of, at least, two of the following criteria: i) RV diastolic diameter>30mm in the parasternal window; ii) RV diameter>left ventricle diameter in the apical or subcostal space; iii) RV free wall hypokinesis; and iv) estimated pulmonary artery systolic pressure>30mmHg. Persistence of RV dysfunction at 48h and 7days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7days after randomization. RESULTS Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48h in 59% (95% confidence interval [CI], 33-82%) of the diclofenac group and in 76% (95% CI, 50-93%) of the placebo group (difference in risk [diclofenac minus standard anticoagulation], -17 percentage points; 95% CI, -47 to 17). Similar proportions (35%) of patients in the diclofenac and placebo groups had persistent RV dysfunction at 7days. Major bleeding occurred in none of patients in the diclofenac group and in 5.9% (95% CI, 0.2-29%) of patient in the placebo group. CONCLUSIONS Due to slow recruitment, our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in normotensive patients with acute PE. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342.