Echocardiographic diagnosis, management and monitoring of pulmonary embolism with right heart thrombus in a patient with myotonic dystrophy: a case report

Acute pulmonary embolism (PE) is a common disease which frequently results in life-threatening right ventricular (RV) failure. High-risk PE, presenting with hypotension, shock, RV dysfunction or right heart thrombus is associated with a high mortality, particularly during the first few hours. Accordingly, it is important to commence effective therapy as soon as possible. In the case described in this report, a 49-year-old woman with myotonic dystrophy type 1 presented with acute respiratory failure and hypotension. Transthoracic echocardiography showed signs of right heart failure and a mobile right heart mass highly suspicious of a thrombus. Based on echocardiographic findings, acute thrombolysis was performed resulting in hemodynamic stabilization of the patient and complete resolution of the right heart thrombus. This case underscores the important role of transthoracic echocardiography for the diagnosis, management and monitoring of PE and underlines the efficacy and safety of thrombolysis in the treatment of PE associated with right heart thrombus

Assessment right atrial thrombus by real-time three dimensional transthoracic echocardiography in patient with dilated cardiomyopathy

We report a case of a 52-year-old patient with dilated cardiomyopathy who presented with worsening heart failure. Two-dimensional transthoracic echocardiography and real-time three dimensional transthoracic echocardiography showed severe dilated cardiac chambers, impaired ejection fraction and a mobile right atrial thrombus 2.6 × 1.0 cm in size, traversing the right atrial cavity during the whole cardiac cycle. After one week therapeutic anticoagulation, echocardiography confirmed no evidence of residual thrombus

Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension

Introduction: In SERAPHIN, a long-term, event-driven, double-blind randomised controlled trial in pulmonary arterial hypertension (PAH), macitentan 10 mg significantly reduced the risk of morbidity/mortality compared with placebo. Its open-label extension study (SERAPHIN OL) further assessed long-term safety and tolerability of macitentan 10 mg in PAH patients. Methods: Patients in SERAPHIN who completed the double-blind treatment period or experienced a morbidity event during the study could enter SERAPHIN OL. Patients received macitentan 10 mg once daily, and safety and survival were assessed until end of treatment (+ 28 days). Two overlapping sets were analysed for safety: (1) all patients in SERAPHIN OL (OL safety set); (2) patients randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Survival was evaluated as an exploratory endpoint in the latter set. Results: Of 742 patients randomised in SERAPHIN, 550 (74.1%) entered SERAPHIN OL (OL safety set); 242 patients were randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Median (min, max) exposure to macitentan 10 mg was 40.1 (0.1, 130.5) months (2074.7 patient-years; OL safety set) and 54.7 (0.1, 141.3) months (1151.0 patient-years; long-term safety/survival set). Safety in both analysis sets was comparable to the known safety profile of macitentan. Kaplan-Meier survival estimates (95% CI) at 1, 5, 7 and 9 years were 95.0% (91.3, 97.1), 73.3% (66.6, 78.9), 62.6% (54.6, 69.6) and 52.7% (43.6, 61.0), respectively (long-term safety/survival set; median follow-up: 5.9 years). Conclusions: This analysis provides the longest follow-up for safety and survival published to date for any PAH therapy. The safety profile of macitentan 10 mg over this extensive treatment period was in line with that observed in SERAPHIN. As the majority of patients were receiving other PAH therapy at macitentan initiation, our study provides additional insight into the long-term safety of macitentan, including as part of combination therapy. Trial Registration: ClinicalTrials.gov Identifiers: NCT00660179 and NCT00667823

Use of bivalirudin for heparin-induced thrombocytopaenia after thrombolysis in massive pulmonary embolism: a case report

A 68-year-old man was referred to the emergency department 6 h after onset of sudden acute dyspnoea. Immediate ECG showed sinus tachycardia with the typical S1-Q3-T3 pattern and incomplete right bundle branch block. The echocardiogram showed the presence of mobile thrombus in the right atrium, a distended right ventricle with free wall hypokinesia and displacement of the interventricular septum towards the left ventricle. Lung spiral computed tomography (CT) showed bilateral pulmonary involvement and confirmed the picture of a thrombotic system in the right atrium and caval vein. Thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) and heparin (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Six hours after thrombolysis bleeding gums and significant reduction in platelet count (around 50,000) were observed. Heparin was discontinued and bivalirudin (0.1 mg/kg bolus and 1.75 mg/kg per h infusion) plus warfarin was initiated and continued for 5 days until the international normalised ratio (INR) was within the therapeutic range (2.0–3.0) for 2 consecutive days, with concomitant platelet count normalisation. Lung spiral and lower abdominal CT before discharge did not show the presence of clots in the pulmonary arteries of the right and left lung. This case suggests that bivalirudin could offer promise for use in patients with heparin-induced thrombocytopaenia (HIT) after thrombolysis for massive pulmonary embolism

Effect of macitentan in pulmonary arterial hypertension and the relationship between echocardiography and cMRI variables: REPAIR echocardiography sub-study results

INTRODUCTION The aim of this sub-study was to evaluate the relationship between echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) variables and to utilize echo to assess the effect of macitentan on right ventricle (RV) structure and function. METHODS REPAIR (NCT02310672) was a prospective, multicenter, single-arm, open-label, 52-week, phase 4 study in pulmonary arterial hypertension (PAH) patients, which investigated the effect of macitentan 10 mg as monotherapy, or in combination with a phosphodiesterase 5 inhibitor, on RV structure, function, and hemodynamics using cMRI and right heart catheterization. In this sub-study, patients were also assessed by echo at screening and at weeks 26 and/or 52. Post hoc correlation analyses between echo and cMRI variables were performed using Pearson's correlation coefficient, Spearman's correlation coefficient, and Bland-Altman analyses. RESULTS The Echo sub-study included 45 patients. Improvements in echo-assessed RV stroke volume (RVSV), left ventricular SV (LVSV), LV end-diastolic volume (LVEDV), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and in 2D global longitudinal RV strain (2D GLRVS) were observed at weeks 26 and 52 compared to baseline. There was a strong correlation between echo (LVSV, 2D GLRVS, and LVEDV) and cMRI variables, with a moderate correlation for RVSV. Bland-Altman analyses showed a good agreement for LVSV measured by echo versus cMRI, whereas an overestimation in echo-assessed RVSV was observed compared to cMRI (bias of - 15 mL). Hemodynamic and functional variables, as well as safety, were comparable between the Echo sub-study and REPAIR. CONCLUSIONS A good relationship between relevant echo and cMRI parameters was shown. Improvements in RV structure and function with macitentan treatment was observed by echo, consistent with results observed by cMRI in the primary analysis of the REPAIR study. Echo is a valuable complementary method to cMRI, with the potential to non-invasively monitor treatment response at follow-up. TRIAL REGISTRATION NUMBER: REPAIR NCT02310672

The REPAIR Study : effects of macitentan on RV structure and function in pulmonary arterial hypertension

Objectives The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC). Background RV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials. Methods REPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints. Results At a prespecified interim analysis in 42 patients, both primary endpoints were met, enrolment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials. Conclusions In the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672

Thrombolysis for massive pulmonary embolism in pregnancy: a case report

Mortality from pulmonary embolism (PE) in pregnancy might be related to challenges in targeting the right population for prevention. Such targeting could help ensure that the correct diagnosis is suspected and adequately investigated, and allow the initiation of the timely and best possible treatment of this disease. In the literature to date only 18 case reports of thrombolysis in pregnant women with PE have been reported, and showed beneficial effects for both mother and fetus in terms of mortality and complications with acceptable bleeding risks. We present here the case of a pregnant patient with massive PE who underwent successful thrombolysis. A 26-year-old pregnant (at 24 weeks) woman was admitted 4 h after onset of sudden acute dyspnea and chest pain. An immediate electrocardiogram showed a typical S1-Q3-T3 pattern. The echocardiogram showed a distended right ventricle with free-wall hypokinesia and displacement of the interventricular septum toward the left ventricle. Thrombolysis with recombinant tissue plasminogen activator (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Pelvic examination and ultrasound showed regular fetal heart beat, and regular placental and liquid presence. No problems developed for the mother or fetus in the subsequent days or at discharge. In conclusion, in pregnant patients with life-threatening massive PE, thrombolytic therapy can be administered, and the use of echocardiographic, laboratory, and clinical data can be useful tools to achieve a rapid diagnosis and make a therapeutic decision, but additional studies need to be performed to further define its use

Acute ECG ST-segment elevation mimicking myocardial infarction in a patient with pulmonary embolism

Pulmonary embolism is a common cardiovascular emergency, but it is still often misdiagnosed due to its unspecific clinical symptoms. Elevated troponin concentrations are associated with greater morbidity and mortality in patients with pulmonary embolism. Right ventricular ischemia due to increased right ventricular afterload is believed to be underlying mechanism of elevated troponin values in acute pulmonary embolism, but a paradoxical coronary artery embolism through opened intra-artrial communication is another possible explanation as shown in our case report

Initial combination therapy with macitentan and tadalafil in patients with pulmonary arterial hypertension, with and without cardiac comorbidities

Aims According to current guidelines, initial monotherapy should be considered for pulmonary arterial hypertension (PAH) patients with cardiopulmonary comorbidities. This analysis of combined data from the TRITON and REPAIR clinical trials, assesses efficacy and safety of initial double combination therapy in patients without vs. with 1–2 cardiac comorbidities. Methods and results Data were combined for patients from TRITON (NCT02558231) and REPAIR (NCT02310672) on initial macitentan and tadalafil double combination therapy (overall set, n = 148) and two subgroups defined as patients without cardiac comorbidities (n = 62) and those with 1–2 cardiac comorbidities (n = 78). Patients with ≥3 comorbidities were excluded from these studies. For the overall set, the median (Q1–Q3) duration of combined macitentan and tadalafil exposure was 513.0 (364.0–778.0) days, and was similar between subgroups. Change from baseline to Week 26 for pulmonary vascular resistance was −55% and −50% for patients without and with 1–2 cardiac comorbidities, respectively; marked improvements in other hemodynamic and functional parameters were also observed, although functional parameters improved to a lesser extent in patients with comorbidities. At Week 26, the majority of patients had improved PAH risk status, according to the non-invasive four-strata and REVEAL Lite 2.0 methods. The safety profile of initial macitentan plus tadalafil combination therapy was consistent with the known profiles of the two drugs, and similar between the subgroups. Conclusions Initial double combination therapy with macitentan plus tadalafil is efficacious in patients with PAH with 1–2 cardiac comorbidities and those without, with similar safety and tolerability profiles between the two groups

Computed tomographic pulmonary angiography and pulmonary embolism: predictive value of a d-dimer assay

<p>Abstract</p> <p>Background</p> <p>Computed tomographic pulmonary angiography (CTPA) is increasingly being used as first investigation for suspected pulmonary embolism (PE). The investigation has high predictive value, but is resource and time intensive and exposes patients to considerable radiation. Our aim was to assess the potential value of a negative d-dimer assay to exclude pulmonary emboli and reduce the number of performed CTPAs.</p> <p>Methods</p> <p>All CTPAs performed in a Scottish secondary care hospital for a fourteen month period were retrospectively reviewed. Collected data included the presence or absence of PE, d-dimer results and patient demographics. PE positive CTPAs were reviewed by a specialist panel.</p> <p>Results</p> <p>Pulmonary embolisms were reported for 66/405 (16.3%) CTPAs and d-dimer tests were performed for 216 (53%). 186/216 (86%) patients had a positive and 30 (14%) a negative d-dimer result. The panel agreed 5/66 (7.6%) false positive examinations. The d-dimer assay's negative predictive value was 93.3% (95% CI = 76.5%-98.8%) based on the original number of positive CTPAs and 100% (95% CI = 85.9%-100%) based on expert review. Significant non-PE intrapulmonary pathology was reported for 312/405 (77.0) CTPAs, including 13 new diagnoses of carcinoma.</p> <p>Conclusions</p> <p>We found that a low d-dimer score excluded all pulmonary embolisms, after a further specialist panel review identified initial false positive reports. However, current evidence-based guidelines still recommend that clinicians combine a d-dimer result with a validated clinical risk score when selecting suitable patients for CTPA. This may result in better use of limited resources, prevent patients being exposed to unnecessary irradiation and prevent potential complications as a result of iodinated contrast.</p