Long-term cardiac computed tomography follow-up after left atrial appendage occlusion.

BACKGROUND: Left atrial appendage occlusion (LAAO) is performed increasingly, but long-term follow-up imaging data are lacking. AIMS: The aim of this study was to evaluate the safety and durability of the Amplatzer Amulet device >4 years after LAAO. METHODS: This was a prospective observational cohort study including 52 patients implanted with the Amplatzer Amulet device at Aarhus University Hospital, Denmark. A >4-year follow-up cardiac computed tomography (CT) scan after LAAO was performed and compared with the results from the 2-month and 12-month scans. The primary outcome was left atrial appendage (LAA) sealing based on distal LAA contrast patency and peridevice leakage (PDL), stratified into complete occlusion (grade 0 [G0]) and grade 1-3 leakage (G1-3), respectively. Secondary outcomes were low- and high-grade hypoattenuated thickening (HAT), device-related thrombosis (DRT) and device durability. RESULTS: The median (interquartile range [IQR]) follow-up time from LAAO to the latest CT scan was 5.8 years (4.5; 6.3). At 2-month (n=52), 12-month (n=27) and >4-year CT follow-ups (n=52), rates of both complete occlusion (33%, 37%, 35%) and G2 leaks (52%, 52%, 48%) remained stable. Rates of G1 leaks varied (14%, 4%, 6%) and G3 leaks rose (2%, 7%, 12%) from earliest to latest follow-up. The median left atrial (LA) volume increased from 127 mL (96; 176) to 144 mL (108; 182) and 147 mL (107; 193). No DRT was found. The structural device integrity was preserved. CONCLUSIONS: This study indicates a stable LAA sealing status throughout the follow-up period, emphasising the importance of the procedural result in avoiding PDL. Few patients displayed PDL progression, which might partly be related to LA remodelling with increasing volume. The long-term device durability appears excellent. Larger studies are warranted to confirm these findings.

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study.

BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

First-in-human left atrial appendage closure using the WATCHMAN FLX Pro device: a case report.

Background: Device-related thrombosis (DRT) is a known complication to left atrial appendage closure (LAAC). The surface of a LAAC device should ideally have antithrombotic properties. The novel WATCHMAN FLX Pro (WFP) incorporates a fluoropolymer-coated fabric membrane designed to increase thromboresistance and facilitate endothelialization. Such features could potentially allow for a minimal post-procedural antithrombotic regimen. Radiopaque platinum markers at the device shoulders and a large 40 mm device are other novel features of the WFP. Case summary: A 75-year-old man with atrial fibrillation was referred for LAAC due to prior subdural haemorrhage during direct-acting anticoagulation treatment. He underwent the first-in-human WFP implantation as part of the WATCHMAN FLX Pro CT study (NCT05567172). Computed tomography (CT) was used for pre-planning, and the procedure was performed under local analgesia guided by intracardiac echocardiography from the left atrium (LA) without any complications. Post-procedural antithrombotic treatment consisted of acetylsalicylic acid 75 mg/day only, and 45-day CT, transoesophageal echocardiography (TEE), and magnetic resonance imaging demonstrated optimal device position with complete LAAC. Hypoattenuated thickening (6 mm) appeared on the device as a smooth surface in continuity with the left atrial wall on CT and TEE. A specific magnetic resonance T1-weighted scan, used for visualization of fresh thrombus, suggested this to represent tissue ingrowth rather than thrombus. Discussion: The advanced follow-up imaging protocol suggested a good WFP implantation result with signs of tissue ingrowth at 45 days. The added radiopaque markers facilitated optimal deployment, evaluation of device stability during tug test, and assessment of device protrusion into the LA.

Changes in Pulmonary Vascular Resistance and Obstruction Score Following Acute Pulmonary Embolism in Pigs.

OBJECTIVES: To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN: Controlled, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (-284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (-8 ± 27 dynes; p = 0.4827) or day 2 (-18 ± 32 dynes; p = 0.0923). CONCLUSIONS: Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.

Single antiplatelet therapy following Amplatzer left atrial appendage occlusion.

BACKGROUND: The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) remains debated. Ideally, this therapy should effectively prevent device-related thrombosis (DRT) while minimising the associated bleeding risk. AIMS: We aimed to evaluate the long-term safety and efficacy of a postprocedural single antiplatelet therapy (SAPT) strategy following Amplatzer LAAO in a large consecutive cohort. METHODS: This retrospective, single-centre, observational study included all patients discharged on SAPT after LAAO with the Amplatzer Cardiac Plug (ACP) or Amplatzer Amulet between March 2010 and December 2021 at Aarhus University Hospital, Denmark. Baseline, procedural, and imaging data were obtained locally, while clinical outcomes and medication data were extracted from the Danish national health registries. RESULTS: A total of 553 patients underwent Amplatzer LAAO during the specified time frame. Of these, 431 (77.9%) high bleeding risk patients were discharged on SAPT with either acetylsalicylic acid (n=403, 72.9%) or clopidogrel (n=28, 5.1%). At 6 months, 173 (41.7%) patients were not on any antithrombotic therapy. The mean CHA2DS2-VASc and HAS-BLED scores were 3.9±1.5 and 3.4±1.1, respectively. DRT was detected in 6 (1.5%) patients on 8-week follow-up imaging using cardiac computed tomography (n=386, 89.6%) or transoesophageal echocardiography (n=27, 6.3%). The 1-year ischaemic stroke rate was 2.2% (95% confidence interval [CI]: 1.1-4.2). One-year rates for major bleeding and cardiovascular death were 5.9% (95% CI: 4.0-8.9) and 2.9% (95% CI: 1.6-5.1), respectively. CONCLUSIONS: SAPT following Amplatzer LAAO displayed rates of DRT and stroke comparable to those reported with more intensive antithrombotic regimens. Meanwhile, we observed low rates of major bleeding.

Left Atrial Appendage Occlusion and Post-procedural Antithrombotic Management.

Left atrial appendage occlusion (LAAO) is an established alternative to oral anticoagulation for stroke prevention in atrial fibrillation. Antithrombotic therapy is used in the post-procedural period to prevent device-related thrombosis (DRT). The risk of DRT is considered highest in the first 45-90 days after device implantation, based on animal studies of the device healing process. Clinically applied antithrombotic regimens vary greatly across studies, continents, and centers. This article gives an overview of the evidence behind current antithrombotic regimens, ongoing randomized trials, and future post-procedural management.

Device-Related Thrombus After Left Atrial Appendage Occlusion: Clinical Impact, Predictors, Classification, and Management.

Despite the unprecedented advances in the left atrial appendage occlusion field, device-related thrombus (DRT) remains an unresolved issue with the therapy. This paper aims to provide a state-of-the-art review of the literature on the incidence, clinical impact, predictors and management of DRT and propose a novel classification of DRT and hypoattenuated thickening.

Computed tomography-based device-sizing in Amplatzer Amulet left atrial appendage occlusion.

BACKGROUND: Amplatzer Amulet is a frequently used device for left atrial appendage occlusion (LAAO). The current sizing protocol is based on the maximum diameter of the left atrial appendage (LAA) landing zone. However, mean, perimeter-, or area-derived diameter might be more accurate measures for device sizing. METHODS: Retrospective analysis of 150 consecutive patients undergoing LAAO is guided by pre-procedural cardiac CT. A total of 117 patients were included; 7 were excluded due to renal failure and 26 due to closure with the sandwich technique. The maximum, mean, area-, and perimeter-derived diameters of the landing zone were derived from pre-procedural cardiac CT scans, and their accuracy to predict the implanted device size was investigated. The predicted device size was determined based on the currently recommended sizing algorithm. Peri-device leak (PDL) was assessed (grade 1-3) along with the underlying mechanism. RESULTS: Device-sizing accuracy was superior for mean, area-, and perimeter derived diameters compared with the maximal diameter, especially for eccentric landing zones. Mean difference between predicted and actually implanted device size was 0.08 mm (± 2.77), 0.30 mm (± 2.40), - 0.39 mm (± 2.43), and - 2.55 mm (± 2.57) across mean, area-derived, perimeter-derived, and maximal diameter, respectively. Grade 3 peri-device leak was seen in 8.5% of implants without a significant association to the eccentricity of the landing zone. The leading mechanism for PDL was device malalignment. CONCLUSION: Our results indicate mean, area-, and perimeter-derived diameters of the device landing zone to perform similar and superior in device-sizing accuracy compared with the maximum diameter.

Cardiac computed tomography following Watchman FLX implantation: device-related thrombus or device healing?

AIMS: Cardiac computed tomography (CT) is increasingly utilized during follow-up after left atrial appendage closure (LAAC). Hypoattenuated thickening (HAT) is a common finding and might represent either benign device healing or device-related thrombosis (DRT). The appearance and characteristics of HAT associated with the Watchman FLX have not been previously described. Therefore, we sought to investigate cardiac CT findings during follow-up after Watchman FLX implantation with a focus on HAT and DRT. METHODS AND RESULTS: Retrospective single-centre, observational study including all patients with successful Watchman FLX implantation and follow-up cardiac CT between March 2019 and September 2021 (n = 244). Blinded analysis of CT images was performed describing the localization, extent, and morphology of HAT and correlated to imaging and histology findings in a canine model. Relevant clinical and preclinical ethical approvals were obtained.Overall, HAT was present in 156 cases (64%) and could be classified as either subfabric hypoattenuation (n = 59), flat sessile HAT (n = 78), protruding sessile HAT (n = 16), or pedunculated HAT (n = 3). All cases of pedunculated HAT and five cases of protruding sessile HAT were considered as high-grade HAT (n = 7). Subfabric hypoattenuation and flat sessile HAT correlated with device healing and endothelialization in histological analysis of explanted devices. CONCLUSION: Subfabric hypoattenuation and flat sessile HAT are frequent CT findings for Watchman FLX, likely representing benign device healing and endothelialization. Pedunculated HAT and protruding HAT are infrequent CT findings that might represent DRT.

Left atrial appendage sealing performance of the Amplatzer Amulet and Watchman FLX device.

BACKGROUND: The left atrial appendage (LAA) sealing properties of the Amplatzer Amulet and Watchman FLX devices were compared using cardiac computed tomography (CT) follow-up. METHODS: Single-center cohort study of patients undergoing LAAO between 2017 and 2020. Two consecutive cohorts were enrolled, one treated with the Amplatzer Amulet (n = 150) up till 2019, and a second cohort treated with the Watchman FLX (n = 150) device from 2019. Cardiac CT was performed 2 months postprocedure. The primary outcome was complete LAA occlusion defined as no visible peri-device leak (PDL) and absence of contrast patency in the distal LAA. Secondary outcomes included PDL, contrast patency without visible PDL, PDL area, and periprocedural complications. RESULTS: Complete occlusion was achieved in 39 (30.5%) of the Amulet group, compared to 89 (71.8%) of the FLX group, p < 0.001. A PDL at the Amulet disc was present in 65 (50.8%), at the lobe in 16 (12.5%), and at both the disc and lobe in 13 (10.2%). For FLX, a PDL was present in 20 (16.1%). Contrast patency without visible PDL was observed in 24 (18.8%) and 15 (12.1%) of the Amulet and FLX group, respectively. The PDL area at the Amulet mid-lobe was 92 mm2 (59-158) and 32 mm2 (IQR 28-96) for FLX, p = 0.019. Device-related thrombosis occurred in 1 (0.7%) and 2 (1.3%), respectively (p = 0.99), with periprocedural adverse events occurring in 6 (4%) and 8 (5.3%) of the Amulet and FLX group (p = 0.79). CONCLUSION: Complete LAA occlusion was achieved in a significantly higher proportion treated with the Watchman FLX compared to the Amulet device. PDL was smaller with the FLX than the Amulet. Conceptual device design differences make interpretation of results complex, and additional studies with clinical outcomes are needed.

Usefulness of a novel sizing chart for left atrial appendage occlusion with the Amplatzer Amulet.

PURPOSE: The present article aims to compare a novel sizing chart based on both maximum and minimum diameters (novel MATRIX) with the current sizing recommendation instructions for use (IFU) based on the maximum diameter. BACKGROUND: Current IFU with the Amulet device are still based on the maximum left atrial appendage (LAA) diameter, which might lead to inappropriate oversizing, especially in elliptic appendages. METHODS: This was a retrospective analysis of patients undergoing LAA occlusion in two high-volume centers. Two hundred patients were included (100 patients with baseline cardiac computed tomography angiography [CCTA] and 100 with baseline 2D and 3D-transesophageal echocardiography [TEE]). The degree of concordance between the predicted device size recommendation and the actual device selection was the primary outcome. RESULTS: The novel MATRIX showed a higher level of concordance between the predicted and implanted device size, regardless of imaging modalities. CCTA showed the strongest, and 2D-TEE the weakest concordance between the predicted and implanted device for both MATRIX and IFU charts. The percentage of patients in whom the disagreement among the predicted and implanted device represented >1 size was higher when using the IFU chart. In elliptical LAA anatomies, the differences favoring the use of MATRIX compared to the IFU in terms of predicted/implanted agreement were higher. Finally, no significant differences in clinical or imaging endpoints were observed between the two different sizing charts. CONCLUSIONS: Incorporating both the LAA maximum and minimum diameters, as opposed to just maximum diameter, appears to improve sizing accuracy. The proposed MATRIX sizing chart offered a higher level of concordance between predicted and implanted device compared to the current IFU.

Predicting factors for pulmonary embolism response team activation in a general pulmonary embolism population.

Pulmonary embolism response teams (PERT) aim to improve treatment of acute pulmonary embolism (PE). PERT focus on intermediate- and high-risk PE patients, but recent multicenter studies show that low-risk PE patients compose one in five of all PERT cases. Conversely, not all intermediate- and high-risk PE patients elicit a PERT activation. The factors leading to PERT activations remain unknown. This study aims to describe the patient characteristics associated with PERT activation for low-risk PE patients and characteristics precluding PERT activation for intermediate/high-risk PE patients. We analysed data from all patients with confirmed PE diagnosed in the Massachusetts General Hospital Emergency Department from August 2013 to February 2017 and cross-referred these data with patients who received a PERT activation and patients who did not. Patients were stratified into low-risk or intermediate/high-risk PE. Univariate analyses were performed within each risk group comparing patients with a PERT activation and patients without. Fifteen percent (56/374) of low-risk PE patients triggered a PERT activation. Patient characteristics associated with PERT activation were: (1) vascular disease, (2) pulmonary diseases, (3) thrombophilia, (4) current use of anticoagulants, (5) central PE and (6) concurrent DVT. Thirty-five percent (110/283) of intermediate/high-risk PE patients did not elicit a PERT activation. Patient characteristics precluding a PERT activation were: (1) vascular disease, (2) malignancies and (3) asymptomatic presentation. Low-risk PE patients with PERT activations had more extensive clot burden, complex comorbidities, or had failed anticoagulation treatment. Intermediate/high-risk PE patients without PERT activations tended to have malignancies or vascular disease.

Left atrial appendage occlusion in haemophilia patients with atrial fibrillation.

PURPOSE: Advanced targeted therapy has resulted in increasing life expectancy and incidence of age-related cardiovascular diseases like atrial fibrillation in patients with haemophilia. Oral anticoagulation constitutes a significant dilemma in this patient category as the risks of stroke and bleeding are difficult to balance. We sought to demonstrate the feasibility of left atrial appendage occlusion (LAAO) in patients with haemophilia and atrial fibrillation. METHODS: All patients with haemophilia treated with LAAO at Aarhus University Hospital, Denmark, were identified from a local prospective database comprising all consecutive LAAO procedures from 2010 up to November 2020. Based on review of the medical records, a retrospective descriptive analysis was performed. RESULTS: Seven patients with haemophilia A and atrial fibrillation underwent LAAO after multidisciplinary conference. Peri-procedural coagulation management was guided by factor VIII activity and treated with repeated bolus administrations of recombinant factor VIII targeting an activity of 100%. The implantation was successful in all patients with only minor bleeding complications post-procedurally. Based on these experiences, a suggested regime has been formulated. CONCLUSIONS: LAAO is feasible in haemophilia patients with concurrent atrial fibrillation. However, special care including intravenous substitution with coagulation factors must be given in the periprocedural management.

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model.

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

Patient and operational factors that influence the decision to place an inferior vena cava filter in a pulmonary embolism response team.

OBJECTIVE: The use of inferior vena cava (IVC) filters is controversial. However, the procedure is widely performed for secondary prophylaxis in patients with severe pulmonary embolism (PE), including those treated by a PE response team (PERT). In this study, we analyzed patient factors associated with the clinical decision to place an IVC filter in PERT patients. METHODS: Data were collected on all Massachusetts General Hospital patients who had a PERT activation from October 1, 2012, to January 29, 2019. Data describing demographics, medical history, PE characteristics and treatment were collected at the time of PERT activation and prospectively for one year after PERT activation. Univariate and multivariable regression analyses were performed to determine factors associated with IVC filter placement. RESULTS: We identified 834 patients, of whom 91 (10.9%) had an IVC filter placed in the first 7 days after PERT activation. The majority of patients receiving an IVC filter were male (55/91 [60.4%]; P =.096) with a mean age of 65 ± 15.0 years. Patients who received an IVC filter were less likely to have had a PERT referral from the Emergency Department (ED) (41/544 [7.5%]; P < .001) and more likely to have been referred from the intensive care unit (24/107 [22.43%]; P ≤ .001) compared with a floor referral. Patients who presented with syncope (15/86 [17.4%]; P = .040), a history of recent trauma (12/41 [29.3%]; P < .001), intracranial hemorrhage (11/39 [28.2%]; P = .002), a recent surgery or invasive procedure (30/188 [16.0%]; P = .012), a recent surgery (29/160 [18.1%]; P = .001) and a recent hospitalization (38/250 [15.2%]; P = .009) were more likely to have an IVC filter placed. Patients receiving an IVC filter were also more likely to have evidence of right heart dysfunction on a computed tomography pulmonary angiogram (61/359 [17.0%]; P < .001) and an echocardiogram (26/144 [18.1%]; P = .003). Compared with patients without an IVC filter, the 30-day venous thromboembolism recurrence rate was higher (4.7% vs 11.0%) in patients with IVC filters (10/45 [22.2%]; P = .023). CONCLUSIONS: Factors associated with venous thromboembolism severity (eg, PERT referral from intensive care unit and right ventricular dysfunction) and an increased bleeding risk (eg, recent surgery or trauma) were associated with IVC filter placement among PERT patients.

Impact of Preload on Right Ventricular Hemodynamics in Acute Pulmonary Embolism.

OBJECTIVES: To compare the hemodynamic effects of increased versus decreased preload in a porcine model of acute intermediate-risk pulmonary embolism. DESIGN: Randomized, controlled animal study. SETTING: Tertiary medical center, animal research laboratory. SUBJECTS: Female, Danish slaughter pigs (n = 22, ~ 60 kg). INTERVENTIONS: Acute pulmonary embolism was induced by large emboli made from clotting of autologous blood. Sixteen animals were randomized to either fluid loading (n = 8, isotonic saline, 1 L/hr for 2 hr) or diuretic treatment (n = 8, furosemide, 40 mg every 30 min, total 160 mg) and compared with a vehicle group (n = 6, no treatment). MEASUREMENTS AND MAIN RESULTS: Hemodynamics were evaluated at baseline, after pulmonary embolism and after each dose by biventricular pressure-volume loops, invasive pressures, diuretic output, respiratory variables, and blood analysis. Pulmonary embolism increased mean pulmonary arterial pressure (p < 0.0001), pulmonary vascular resistance (p = 0.008), right ventricular arterial elastance (p = 0.003), and right ventricular end-systolic volume (p = 0.020) while right ventricular stroke volume and right ventricular ejection fraction were decreased (p = 0.047 and p = 0.0003, respectively) compared with baseline. Fluid loading increased right ventricular end-diastolic volume (+31 ± 13 mL; p = 0.004), right ventricular stroke volume (+23 ± 10 mL; p = 0.009), cardiac output (+2,021 ± 956 mL; p = 0.002), and right ventricular ejection fraction (+7.6% ± 1.5%; p = 0.032), whereas pulmonary vascular resistance decreased (-202 ± 65 dynes; p = 0.020) compared with vehicle. Diuretic treatment decreased right ventricular end-diastolic volume (-84 ± 11 mL; p < 0.001), right ventricular stroke volume (-40 ± 6 mL; p = 0.001), cardiac output (-3,327 ± 451 mL; p = 0.005), and mean pulmonary arterial pressure (-7 ± 1 mm Hg; p < 0.001) and increased right ventricular end-systolic elastance (+0.72 ± 0.2 mm Hg/mL; p < 0.001) and systemic vascular resistance (+1,812 ± 767 dynes; p < 0.001) with no effects on mean arterial pressure. CONCLUSIONS: In a porcine model of acute intermediate-risk pulmonary embolism, fluid loading increased right ventricular preload and right ventricular stroke volume, whereas diuretics decreased right ventricular preload and right ventricular stroke volume without affecting mean arterial pressure.

Inhaled nitric oxide has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute pulmonary embolism.

BACKGROUND: Inhaled nitric oxide (iNO) effectively reduces right ventricular afterload when administered in the immediate phase of acute pulmonary embolism (PE) in preclinical animal models. In a porcine model of intermediate-risk PE, we aimed to investigate whether iNO has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute PE. METHODS: Anesthetized pigs (n = 18) were randomized into three subgroups. An acute PE iNO-group (n = 6) received iNO at 40 ppm at one, three, six, nine and 12 hours after onset of PE. Vehicle animals (n = 6) received PE, but no active treatment. A third group of sham animals (n = 6) received neither PE nor treatment. Animals were evaluated using intravascular pressures, respiratory parameters, biochemistry and intracardiac pressure-volume measurements. RESULTS: The administration of PE increased mean pulmonary artery pressure (mPAP) (vehicle vs sham; 33.3 vs 17.7 mmHg, p < 0.0001), pulmonary vascular resistance (vehicle vs sham; 847.5 vs 82.0 dynes, p < 0.0001) and right ventricular arterial elastance (vehicle vs sham; 1.2 vs 0.2 mmHg/ml, p < 0.0001). Significant mPAP reduction by iNO was preserved at 12 hours after the onset of acute PE (vehicle vs iNO; 0.5 vs -3.5 mmHg, p < 0.0001). However, this response was attenuated over time (p = 0.0313). iNO did not affect the systemic circulation. CONCLUSIONS: iNO is a safe and effective pulmonary vasodilator both in the immediate and prolonged phase of acute PE in an in-vivo porcine model of intermediate-risk PE.

Right ventricular adaptation in the critical phase after acute intermediate-risk pulmonary embolism.

BACKGROUND: The haemodynamic response following acute, intermediate-risk pulmonary embolism is not well described. We aimed to describe the cardiovascular changes in the initial, critical phase 0-12 hours after acute pulmonary embolism in an in-vivo porcine model. METHODS: Pigs were randomly allocated to pulmonary embolism (n = 6) or sham (n = 6). Pulmonary embolism was administered as autologous blood clots (20 × 1 cm) until doubling of mean pulmonary arterial pressure or mean pulmonary arterial pressure was greater than 34 mmHg. Sham animals received saline. Cardiopulmonary changes were evaluated for 12 hours after intervention by biventricular pressure-volume loop recordings, invasive pressure measurements, arterial and central venous blood gas analyses. RESULTS: Mean pulmonary arterial pressure increased (P < 0.0001) and stayed elevated for 12 hours in the pulmonary embolism group compared to sham. Pulmonary vascular resistance and right ventricular arterial elastance (right ventricular afterload) were increased in the first 11 and 6 hours, respectively, after pulmonary embolism (P < 0.01 for both) compared to sham. Right ventricular ejection fraction was reduced (P < 0.01) for 8 hours, whereas a near-significant reduction in right ventricular stroke volume was observed (P = 0.06) for 4 hours in the pulmonary embolism group compared to sham. Right ventricular ventriculo-arterial coupling was reduced (P < 0.05) for 6 hours following acute pulmonary embolism despite increased right ventricular mechanical work in the pulmonary embolism group (P < 0.01) suggesting right ventricular failure. CONCLUSIONS: In a porcine model of intermediate-risk pulmonary embolism, the increased right ventricular afterload caused initial right ventricular ventriculo-arterial uncoupling and dysfunction. After approximately 6 hours, the right ventricular afterload returned to pre-pulmonary embolism values and right ventricular function improved despite a sustained high pulmonary arterial pressure. These results suggest an initial critical and vulnerable phase of acute pulmonary embolism before haemodynamic adaptation.

Right ventricular adaptation in the critical phase after acute intermediate-risk pulmonary embolism.

BACKGROUND: The haemodynamic response following acute, intermediate-risk pulmonary embolism is not well described. We aimed to describe the cardiovascular changes in the initial, critical phase 0-12 hours after acute pulmonary embolism in an in-vivo porcine model. METHODS: Pigs were randomly allocated to pulmonary embolism (n = 6) or sham (n = 6). Pulmonary embolism was administered as autologous blood clots (20 × 1 cm) until doubling of mean pulmonary arterial pressure or mean pulmonary arterial pressure was greater than 34 mmHg. Sham animals received saline. Cardiopulmonary changes were evaluated for 12 hours after intervention by biventricular pressure-volume loop recordings, invasive pressure measurements, arterial and central venous blood gas analyses. RESULTS: Mean pulmonary arterial pressure increased (P < 0.0001) and stayed elevated for 12 hours in the pulmonary embolism group compared to sham. Pulmonary vascular resistance and right ventricular arterial elastance (right ventricular afterload) were increased in the first 11 and 6 hours, respectively, after pulmonary embolism (P < 0.01 for both) compared to sham. Right ventricular ejection fraction was reduced (P < 0.01) for 8 hours, whereas a near-significant reduction in right ventricular stroke volume was observed (P = 0.06) for 4 hours in the pulmonary embolism group compared to sham. Right ventricular ventriculo-arterial coupling was reduced (P < 0.05) for 6 hours following acute pulmonary embolism despite increased right ventricular mechanical work in the pulmonary embolism group (P < 0.01) suggesting right ventricular failure. CONCLUSIONS: In a porcine model of intermediate-risk pulmonary embolism, the increased right ventricular afterload caused initial right ventricular ventriculo-arterial uncoupling and dysfunction. After approximately 6 hours, the right ventricular afterload returned to pre-pulmonary embolism values and right ventricular function improved despite a sustained high pulmonary arterial pressure. These results suggest an initial critical and vulnerable phase of acute pulmonary embolism before haemodynamic adaptation.