Pulmonary Vasodilation by Sildenafil in Acute Pulmonary Embolism—A Randomized Explorative Trial

Abstract Background: To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).Methods: Patients with PE were randomized to a single oral dose of sildenafil 50mg (n=10) or placebo (n=10) as add-on to conventional therapy. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR.Results: Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p=0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p=0.97).Conclusion: A single oral dose of 50 mg sildenafil did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE.Trial Registration: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1

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Pulmonary Vasodilation by Sildenafil in Acute Intermediate-High Risk Pulmonary Embolism – A Randomized Explorative Trial

10.21203/rs.3.rs-17489/v2 ◽

2020 ◽

Author(s):

Asger Andersen ◽

Farhad Waziri ◽

Jacob Gammelgaard Schultz ◽

Sarah Holmboe ◽

Søren Warberg Becker ◽

...

Keyword(s):

Blood Pressure ◽

Pulmonary Embolism ◽

High Risk ◽

Cardiac Index ◽

Oral Dose ◽

Right Ventricular ◽

Single Oral Dose ◽

Ventricular Function ◽

Right Ventricular Function ◽

Pulmonary Vasodilation

Abstract Background: To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE). Methods: Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50mg (n=10) or placebo (n=10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR. Results: Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p=0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p=0.97). Conclusion: A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results.

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Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01440-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Asger Andersen ◽

Farhad Waziri ◽

Jacob Gammelgaard Schultz ◽

Sarah Holmboe ◽

Søren Warberg Becker ◽

...

Keyword(s):

Blood Pressure ◽

Pulmonary Embolism ◽

High Risk ◽

Cardiac Index ◽

Oral Dose ◽

Right Ventricular ◽

Single Oral Dose ◽

Ventricular Function ◽

Right Ventricular Function ◽

Pulmonary Vasodilation

Abstract Background To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE). Methods Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5–1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR. Results Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (− 19 ± 10 mmHg, p < 0.001) which was not observed in the placebo group (0 ± 9 mmHg, p = 0.97). Conclusion A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results. Trial Registration: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1.

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A patient with pulmonary embolism takes a surprising HIT: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab304 ◽

2021 ◽

Author(s):

Yishay Wasserstrum ◽

Aharon Lubetzky ◽

Orly Goitein ◽

Shlomo Matetzky

Keyword(s):

Pulmonary Embolism ◽

High Risk ◽

Right Ventricular ◽

Ventricular Function ◽

Right Ventricular Function ◽

Clinical Investigation ◽

Complete Recovery ◽

Initial Therapy ◽

Fibrinolytic Therapy ◽

Catheter Directed Thrombolysis

Abstract Background Venous thromboembolism (VTE) is a common condition that may manifest as intermediate or high-risk pulmonary embolism (PE), requiring either primary or subsequent fibrinolytic therapy. In these cases, catheter-directed thrombolysis (CTD) has been shown to be beneficial. Case Summary We present the case of a borderline obese but otherwise healthy 43-year-old male individual, who was admitted with acute intermediate-high risk PE requiring treatment with intravenous unfractionated heparin. After initial therapy failure, the patient received CDT, with subsequent clinical worsening, and a mixed result of imaging studies suggesting partial central worsening and partial peripheral improvement of the thrombotic burden and right ventricular function. A after a multidisciplinary pulmonary embolism response team (PERT) consultation, the diagnosis of heparin-induced thrombocytopenia with normal platelet levels was made. Therapy was changed to intravenous Bivalirudin, with an excellent clinical response and complete recovery of right-ventricular function. The patient was discharged with oral Apixaban therapy, and on follow-up was otherwise well. Discussion Apparent failure of thrombolytic therapy for VTE warrants a clinical investigation into possible causes of a pro-thrombotic state. In this case, the diagnosis of HIT was surprising, especially due only a mild decline in platelet levels, that were well within normal range. We also acknowledge the significance of our PERT in the key diagnosis made in this case.

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