Prospective Multicenter International Registry of Ultrasound-Facilitated Catheter-Directed Thrombolysis in Intermediate-High and High-Risk Pulmonary Embolism (KNOCOUT PE).

BACKGROUND: Prior clinical trials have demonstrated the efficacy of ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk pulmonary embolism (PE) using reduced thrombolytic doses and shorter infusion durations. However, utilization and safety of such strategies in broader PE populations remain unclear. The KNOCOUT PE (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) registry is a multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes. METHODS: The KNOCOUT PE prospective cohort included 489 patients (64 sites internationally) with acute intermediate-high or high-risk PE treated with USCDT between March 2018 and June 2020. Principal safety outcomes were independently adjudicated International Society on Thrombosis and Haemostasis major bleeding at 72 hours post-treatment and mortality within 12 months of treatment. Additional outcomes included change in right ventricular/left ventricular ratio and quality of life measures over 12 months. RESULTS: Mean alteplase (r-tPA [recombinant tissue-type plasminogen activator]) infusion duration was 10.5 hours. Mean total r-tPA dose was 18.1 mg, with 31.0% of patients receiving ≤12 mg. Major bleeding events within 72 hours occurred in 1.6% (8/489) of patients. One patient experienced worsening of a preexisting subdural hematoma after USCDT and therapeutic anticoagulation, which ultimately required surgery. All-cause mortality at 30 days was 1.0% (5/489). Improvement in PE quality of life score was observed with a 41.1% (243/489, 49.7%) and 44.2% (153/489, 31.3%) mean relative reduction by 3 and 12 months, respectively. CONCLUSIONS: In a prospective observational cohort study of patients with intermediate-high and high-risk PE undergoing USCDT, mean r-tPA dose was 18 mg, and the rates of major bleeding and mortality were low. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03426124.

Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study.

BACKGROUND: Due to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE). METHODS AND RESULTS: The Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. CONCLUSIONS: Regardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.

One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism.

BACKGROUND: Accelerated tPA (tissue-type plasminogen activator) dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis improve short-term computed tomographic-measured right ventricular (RV)-to-left ventricular diameter ratio in massive and submassive pulmonary embolism. The impact on RV remodeling, functional status, and quality of life over the long-term remains unclear. METHODS: To study 1-year changes in RV remodeling, functional status, and quality of life, we assessed patients with acute submassive pulmonary embolism randomly assigned to 1 of 4 tPA dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis in the OPTALYSE-PE trial (Optimum Duration and Dose of r-tPA With the Acoustic Pulse Thrombolysis Procedure for Intermediate-Risk Pulmonary Embolism; 8 mg/2 hours, 8 mg/4 hours, 12 mg/6 hours, and 24 mg/6 hours). Echocardiographic assessment included RV-to-left ventricular diameter ratio within 4 hours of treatment end, and at 48 hours, 30 days, 90 days, and 1 year. Functional status was assessed by 6-minute walk test at 30 days, 90 days, and 1 year and PROMIS-PF-6b scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Quality of life was evaluated by PEmb-QOL scores at 30 days, 90 days, 180 days, 270 days, and 1 year. RESULTS: Mean RV-to-left ventricular diameter ratio decreased from baseline to 4 hours and further at 48 hours and 30 days, with reductions maintained at 90 days and 1 year in all groups. Mean 6-minute walk distance, PROMIS-PF-6b, and PEmb-QOL scores improved over the course of 1 year in all groups. CONCLUSIONS: Accelerated lower-dose tPA regimens for ultrasound-facilitated, catheter-directed fibrinolysis resulted in sustained recovery of RV-to-left ventricular diameter ratio and tricuspid annular plane systolic excursion and improvements in functional status and quality of life over 1 year. Registration: URL: https://www.ClinicalTrials.gov. Unique Identifier: NCT02396758.

Ultrasound-Accelerated Thrombolysis and Venoplasty for the Treatment of the Postthrombotic Syndrome: Results of the ACCESS PTS Study.

Background Postthrombotic syndrome is a common complication of deep vein thrombosis, with limited treatment options. Methods and Results ACCESS PTS (Accelerated Thrombolysis for Post-Thrombotic Syndrome Using the Acoustic Pulse Thrombolysis Ekosonic Endovascular System) is a multicenter, single-arm, prospective study evaluating patients with chronic deep vein thrombosis and postthrombotic syndrome (Villalta score ≥8) who received minimum 3 months of anticoagulation. Patients underwent percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis, with data collected on clinical characteristics, postthrombotic syndrome, imaging, and quality of life to 1 year. The primary efficacy outcome was a reduction of ≥4 points in the Villalta score 30 days after procedure. The primary safety outcomes were major bleeding episodes within 72 hours and symptomatic pulmonary embolism during the index hospitalization. A total of 82 limbs (78 patients) were treated (age, 54.6±12.7 years; 32.1% women; mean Villalta score, 15.5±5.2). The primary end point was met in 64.6% (51/79). At 1 year, 77.3% (51/66) of limbs continued with a Villalta reduction ≥4. At 365 days, >90% of segments had patency with ultrasound flow present. Baseline to 1-year Physical Component Summary mean score of the Short Form-36 increased from 38.9±9.5 to 45.2±9.8 (P≤0.0001), and mean VEINES-QOL (Venous Insufficiency Epidemiological and Economic Study-Quality of Life) increased from 61.9±19.7 to 82.6±20.8 at 1 year (P<0.0001). Iliofemoral venous stenting was performed in 42 patients, with similar improvements seen in all outcomes, regardless of stenting status. One patient developed severe bleeding within 72 hours of the intervention and died at 32 days after procedure (1.3% mortality rate). Conclusions Percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis resulted in successful recanalization of chronic venous obstruction with improved postthrombotic syndrome severity and quality of life. Results were sustained at 1-year after procedure. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02159521.

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study.

OBJECTIVES: This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND: Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS: Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS: Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS: Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Ultrasound-accelerated catheter-directed thrombolysis for acute submassive pulmonary embolism.

PURPOSE: To evaluate the safety and efficacy of ultrasound-accelerated catheter-directed thrombolysis (USAT) in patients with submassive pulmonary embolism (PE). MATERIALS AND METHODS: This retrospective study comprised 45 consecutive patients (15 prospective, 30 retrospective) who underwent USAT for submassive PE from June 2012-May 2014. Inclusion criteria were right ventricular dysfunction (RVD) as indicated by right ventricle-to-left ventricle (RV:LV) ratio > 0.9, symptoms of < 2 weeks' duration, and absence of absolute contraindication to thrombolysis. All patients underwent pulmonary artery catheterization with a standardized protocol (24 mg recombinant tissue plasminogen activator). Hemodynamic evaluation immediately after USAT, RV:LV ratio evaluation at 48-72 hours after USAT by computed tomography angiography and echocardiography, and adverse event reporting for a minimum of 30 days were performed. Outcomes and complications are reported as per the Society of Interventional Radiology Reporting Standards for Endovascular Treatment of Pulmonary Embolism. RESULTS: USAT was technically successful in 100% (n = 45) of patients. Main pulmonary artery pressure significantly decreased from 49.8 mm Hg to 31.1 mm Hg (P < .0001). RVD significantly improved with mean RV:LV ratios decreasing from 1.59 to 0.93 (P < .0001). There were 6 complications: 4 minor bleeding episodes at access sites and 2 major bleeding complications (flank and arm hematoma). All-cause mortality at 30 days was 0%. There were no readmissions for PE at 30 days after discharge. CONCLUSIONS: Ultrasound-accelerated catheter-directed thrombolysis using a standardized low-dose protocol is a safe and efficacious method of treatment of submassive PE to reduce acute pulmonary hypertension and RVD.

Early results from a United States trial of prostatic artery embolization in the treatment of benign prostatic hyperplasia.

PURPOSE: To report early findings from a prospective United States clinical trial to evaluate the efficacy and safety of prostatic artery embolization (PAE) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From January 2012 to March 2013, 72 patients were screened and 20 patients underwent treatment. Patients were evaluated at baseline and selected intervals (1, 3, and 6 mo) for the following efficacy variables: American Urological Association (AUA) symptom score, quality of life (QOL)-related symptoms, International Index of Erectile Function score, peak urine flow rate, and prostate volume (on magnetic resonance imaging at 6 mo). Complications were monitored and reported per Society of Interventional Radiology guidelines. RESULTS: Embolization was technically successful in 18 of 20 patients (90%); bilateral PAE was successful in 18 of 19 (95%). Unsuccessful embolizations were secondary to atherosclerotic occlusion of prostatic arteries. Clinical success was seen in 95% of patients (19 of 20) at 1 month, with average AUA symptom score improvements of 10.8 points at 1 month (P < .0001), 12.1 points at 3 months (P = .0003), and 9.8 points at 6 months (P = .06). QOL improved at 1 month (1.9 points; P = .0002), 3 months (1.9 points; P = .003), and 6 months (2.6 points; P = .007). Sexual function improved by 34% at 1 month (P = .11), 5% at 3 months (P = .72), and 16% at 6 months (P = .19). Prostate volume at 6 months had decreased 18% (n = 5; P = .05). No minor or major complications were reported. CONCLUSIONS: Early results from this clinical trial indicate that PAE offers a safe and efficacious treatment option for men with BPH.

Utility of cone-beam CT imaging in prostatic artery embolization.

PURPOSE: To evaluate the utility of cone-beam computed tomography (CT) in patients undergoing prostatic artery (PA) embolization (PAE) for benign prostatic hyperplasia. MATERIALS AND METHODS: From January 2012 to January 2013, 15 patients (age range, 59-81 y; mean, 68 y) with moderate- or severe-grade lower urinary tract symptoms, in whom medical management had failed were enrolled in a prospective United States trial to evaluate PAE. During pelvic angiography, 15 cone-beam CT acquisitions were performed in 11 patients, and digital subtraction angiography was performed in all patients. Cone-beam CT images were reviewed to assess for sites of potential nontarget embolization that impacted therapy, a pattern of enhancement on cone-beam CT suggesting additional PAs, confirmation of prostatic parenchymal perfusion before embolization, and contralateral prostatic parenchymal enhancement. RESULTS: Cone-beam CT was successful in 14 of 15 acquisitions, and PAE was successful in 14 of 15 patients (92%). Cone-beam CT provided information that impacted treatment in five of 11 patients (46%) by allowing for identification of sites of potential nontarget embolization. Duplicated prostatic arterial supply and contralateral perfusion were each identified in 21% of patients (three of 11). Prostatic perfusion was confirmed before embolization in 50% of acquisitions (seven of 14). CONCLUSIONS: Cone-beam CT is a useful technique that can potentially mitigate the risk of nontarget embolization. During treatment, it can allow for the interventionalist to identify duplicated prostatic arterial supply or contralateral perfusion, which may be useful when evaluating a treatment failure.

Geniculate artery embolization in the management of spontaneous recurrent hemarthrosis of the knee: case series.

Spontaneous recurrent hemarthrosis after knee arthroplasty is reported to occur in 0.3%-1% of patients, likely secondary to hypertrophic vascular synovium. Five patients who underwent previous arthroplasty presented with spontaneous hemarthrosis. Selective arterial embolization was performed with spherical embolic particles (diameter range, 100-700 µm). Angiography demonstrated synovial hypervascularity with geniculate artery "tumor blush" appearance in all patients. Average time to resolution of effusion was 2.6 weeks, with no recurrences reported during follow-up (mean, 25.4 mo; range, 16-48 mo). Two patients experienced transient cutaneous ischemia. Selective geniculate artery embolization with spherical embolic particles is an effective treatment for spontaneous recurrent hemarthrosis of the knee.

Uterine artery embolization versus myomectomy: a multicenter comparative study.

OBJECTIVE: To determine whether there is significant quality of life score improvement after uterine artery embolization (UAE) and to compare UAE and myomectomy outcomes. DESIGN: Prospective cohort controlled study. SETTING: Sixteen medical centers in the United States. PATIENT(S): One hundred forty-nine UAE patients and 60 myomectomy patients. Patients were assigned to myomectomy or UAE on the basis of a best treatment decision made by the patient and her physician. All patients were observed for 6 months. The UAE patients also had follow-up examinations at 1 year. INTERVENTION(S): Myomectomy or UAE. MAIN OUTCOME MEASURE(S): Quality of life score changes, menstrual bleeding score changes, uterine size differences, time off, and adverse events. RESULT(S): Both groups experienced statistically significant improvements in the uterine fibroid quality of life score, menstrual bleeding, uterine volume, and overall postoperative quality of life. The mean hospital stay was 1 day for the UAE patients, compared with 2.5 days for the myomectomy patients. The UAE and myomectomy patients returned to their normal activities in 15 days and 44 days, respectively, and returned to work in 10 days and 37 days, respectively. At least one adverse event occurred in 40.1% of the myomectomy patients, compared with 22.1% in the UAE group. CONCLUSION(S): The uterine fibroid quality of life score was significantly improved in both groups. No significant differences were observed in bleeding improvement, uterine volume reduction, uterine fibroid quality of life score improvement, and overall quality of life score improvement between groups. Patients receiving UAE required fewer days off work, fewer hospital days, and experienced fewer adverse events.

I. Uterine fibroid embolization: preprocedure assessment.

Increasing clinical experience with uterine fibroid embolization (UFE) has improved the ability of interventionalist radiologists to discern who is and who is not an appropriate candidate for this procedure. Initial evaluation should be directed at obtaining answers to the following key questions: (1) Does the patient have uterine fibroids that account for her symptoms and are they severe enough to require invasive treatment? (2) Does she desire future childbearing? (3) Are there any clinical indications or imaging signs of uterine malignancy? (4) Are there any medical or anatomic features that would favor a particular therapeutic modality? (5) What are her own preferences regarding treatment? Ultrasound and magnetic resonance imaging are vital elements to the assessment and planning of the appropriate course of action. Given the lack of prospective comparative trials between UFE and surgical treatment, recommendations are often highly influenced by patient preference.

V. Uterine fibroid embolization: management of complications.

Fortunately, the number of complications reported after uterine fibroid embolization (UFE) is extremely low. Angiographic mishap or drug reaction are probably more common than purely UFE-related complications. However, the possibility of infection or necrosis of the uterus, with their significant attendant morbidity, is a sobering reminder that embolotherapy can have a powerful impact on the target organ(s). Knowledge of the expected time course for symptom resolution and the often confusing imaging findings shortly after UFE are critical for avoiding unnecessary delay in surgical intervention or, perhaps more important, an inappropriate rush to surgery when antibiotics alone will suffice. Other complications include alteration of uterine physiology, which may disrupt sexual function, and menstrual irregularity and even premature menopause.

VI. Uterine fibroid embolization: developing a clinical service.

Building a uterine fibroid embolization (UFE) practice can be a complex process. Choices must be made regarding whether to align oneself with a gynecologist or to accept direct referrals. For the interventional radiologist, the responsibilities of evaluation and patient care pose unique and time-consuming administrative and clinical challenges. Physician extenders, either nurse practitioners or physician's assistants, play key roles as clinical coordinators by guiding the patient through the medical system and making certain that she is cleared for the procedure medically and logistically. In some settings, they may also assist in many of the technical aspects of the procedure and postoperative care. Interventional radiologists must be prepared for battles with insurance companies and be willing to go through the appeals process. Business officers must also be trained to properly code for the procedures to insure optimal reimbursement. The success of building a UFE practice may also be bolstered by directly marketing to patients and by providing them with access via the Internet.