Letter to the Editor

Risk stratification of normotensive pulmonary embolism based on the sPESI — Does it work for all patients?

No se ha aclarado completamente si se debería realizar una ecocardiografía a los pacientes con tromboembolia de pulmón (TEP) de riesgo bajo.

Realizamos un metanálisis de estudios observacionales que incluyeron pacientes con TEP de riesgo bajo para determinar el significado pronóstico de la disfunción ecocardiográfica del ventrículo derecho (VD). El evento primario considerado fue la muerte por cualquier causa a corto plazo. El evento secundario fue la muerte por la propia TEP a corto plazo. Utilizamos un modelo de efectos aleatorios para combinar los resultados, la prueba de correlación de rangos de Begg para estimar el sesgo de publicación y la prueba de la I² para evaluar la heterogeneidad de los estudios incluidos.

Identificamos once estudios observacionales que incluyeron 1.868 pacientes con TEP de riesgo bajo. Diez de los 447 (2,2%) pacientes con TEP de riesgo bajo y disfunción del VD fallecieron, comparado con 10 de los 1.421 (0,7%) pacientes sin disfunción del VD. La presencia de disfunción ecocardiográfica del VD no se asoció con la mortalidad precoz por cualquier causa (odds ratio 2,0; intervalo de confianza del 95%, 0,8-5,1, P = 0,14; I² = 8%), pero se asoció de forma significativa con la muerte por la propia TEP (odds ratio 5,2; intervalo de confianza del 95% 1,7-16, P < 0,01; I² = 0%).

En pacientes con TEP de riesgo bajo, la disfunción ecocardiográfica del VD no se asocia significativamente a la muerte por cualquier causa pero se asocia de forma significativa a la muerte por la propia TEP.

It is unclear whether low-risk patients with acute symptomatic pulmonary embolism (PE) should undergo echocardiogram.

We performed a meta-analysis of studies that enrolled patients with acute low-risk PE to assess the prognostic value of echocardiographic diagnosis of right ventricular (RV) dysfunction for the primary outcome of short-term all-cause mortality, and the secondary outcome of short-term PE-related mortality. We used a random-effects model to pool study results, a Begg rank correlation method to evaluate for publication bias, and I² testing to assess heterogeneity.

The meta-analysis included a total of 11 studies 1,868 patients with low-risk PE. Ten of the 447 (2.2%; 1.1%-4.1%) low-risk patients with echocardiographic RV dysfunction died soon after the diagnosis of PE compared with 10 of 1,421 (0.7%; 0.3-1.3%) patients without RV dysfunction. RV dysfunction was not significantly associated with short-term all-cause mortality (odds ratio 2.0; 95% confidence interval, 0.8-5.1, p = .14; I² = 8%). RV dysfunction was significantly associated with short-term PE-related mortality (odds ratio 5.2; 95% confidence interval, 1.7-16, p < .01; I² = 0%).

In patients with low-risk PE, echocardiographic RV dysfunction is not associated with all-cause mortality, but identifies patients with an increased risk for short-term PE-related mortality.

We report the case of a 61-year-old man who presented at the Emergency Department (ED), complaining of sudden-onset dyspnea and chest pain after a long flight from Tokyo to Houston. Considering his clinical stability and sPESI 0, enoxaparin 1 mg/kg BID was started for 24 h, and the patient was then considered for early discharge with apixaban 10 mg BID. Direct-factor Xa inhibition did not improve extensive thrombus burden and right ventricular dysfunction despite D-dimer measurement reduction. Because of the treatment failure, we considered thrombolysis. Currently, recommendations to use thrombolysis in patients under non-vitamin K antagonist oral anticoagulants (NOACs) do not exist. Hence, the one dose of apixaban was stopped, and 12 h later, we performed successful thrombolysis. A systematic review from 2007 to 2017 did not identify any cases related to NOACs failure to reduce thrombus burdens in patients with PE and persistent right ventricular dysfunction. We also did not find any evidence of cases that reported strategies for urgent thrombolysis in PE patients on NOACs. To the best of our knowledge, apixaban's failure to reduce thrombus burden, persistent right ventricular dysfunction, and a NOACs-thrombolysis bridge in patients with PE on apixaban has not been previously described. Both the bedside risk stratification and the therapeutic failures should alert clinicians in the ED to the potential limitations of low-molecular-weight heparin, NOACs therapy, and sPESI in the setting of intermediate-high-risk PE.

Risk stratification of normotensive patients with acute pulmonary embolism (PE) includes the assessment of right ventricular dysfunction (RVD), biomarker levels, and a clinical score as suggested by the 2014 guidelines of the European Society of Cardiology (ESC). We performed an external validation of the prognostic performance of Heart-type Fatty Acid Binding Protein (H-FABP) and incorporated it into the new ESC algorithm.

H-FABP was measured by fully-automated immunoturbidimetry in 716 patients from the PROTECT study (PROgnosTic valuE of CT scan in haemodynamically stable patients with acute symptomatic PE).

H-FABP ranged from 0.7 to 123.6 ng/ml (median 4.13; IQR, 2.53–6.61) and was above the cut-off of 6 ng/ml in 209 patients (29.2%). A complicated course within 30 days (death, catecholamine administration, mechanical ventilation, resuscitation) occurred in 1.1% (n = 3) of the 271 low risk patients with a simplified Pulmonary Embolism Severity Index (sPESI) of 0 and was particular low (0.4%), if H-FABP levels were normal. In the case of elevated H-FABP, 4.3% of patients suffered complications despite sPESI of 0. The risk for an adverse 30-day outcome increased for patients of the intermediate-low and intermediate-high risk group and was highest for the combination of sPESI ≥1 with RVD on MDCT and elevated H-FABP (odds ratio 12.3, 95% confidence interval, 3.49–43.32; P < 0.001).

H-FABP is suitable for risk stratification of normotensive PE patients if integrated in the new ESC algorithm and may help to identify patients with higher risk for adverse clinical events.

Right ventricular (RV) dysfunction has proved to be an important predictor of morbidity and mortality in patients with pulmonary embolism (PE). Tricuspid annular plane systolic excursion (TAPSE) is one of the parameters that have been validated as predictor of outcomes. The aim of our study was to evaluate the performance (sensitivity and specificity) of high-sensitivity cardiac troponin T (hs-cTnT) to predict RV dysfunction defined as TAPSE < 16 mm.

We conducted a single-center retrospective analysis of 40 patients prospectively included. Median age was 66 years (59–76) and PESI score was 81 (67–100).

Right ventricular dysfunction was present in 30% of the patients and was associated with higher median troponin values (33.5 ng/L vs 16 ng/L; P= .03). A logarithmic relation was observed between hs-cTnT and lower TAPSE values (r²= 0.36; P< .0001). The area under the ROC curve of hs-cTnT to predict RV dysfunction was 0.77 (0.63–0.92).

hs-cTnT is a biomarker with good performance to identify RV dysfunction in PE.

Pulmonary embolism (PE) remains a major contributor to global disease burden. Risk-adapted treatment and follow-up contributes to a favorable outcome. Age-adjusted cutoff levels increase D-dimer specificity and may decrease overuse of imaging procedures and overdiagnosis of PE. Primary systemic fibrinolysis has an unfavorable risk–benefit ratio in intermediate-risk PE; catheter-directed techniques are an option for patients with hemodynamic decompensation and high bleeding risk. New oral anticoagulant agents are effective and safe alternatives to standard anticoagulation regimens. Recent trial data do not support insertion of cava filters in patients who can receive anticoagulant treatments. Remaining areas of uncertainty include the therapeutic implications of subsegmental PE, the optimal diagnostic approach to the pregnant patient with suspected PE, and the efficacy and safety of new oral anticoagulant agents in patients with cancer. Campaigns to increase awareness combined with strategies to implement guideline recommendations will be crucial steps towards further optimizing management of acute PE.