Mechanical Support in High-Risk Pulmonary Embolism: Review Article.

Acute pulmonary embolism (PE) may manifest with mild nonspecific symptoms or progress to a more severe hemodynamic collapse and sudden cardiac arrest. A substantial thrombotic burden can precipitate sudden right ventricular strain and failure. Traditionally, systemic thrombolytics have been employed in such scenarios; however, patients often present with contraindications, or these interventions may prove ineffective. Outcomes for this medically complex patient population are unfavorable, necessitating a compelling argument for advanced therapeutic modalities or alternative approaches. Moreover, patients frequently experience complications beyond hemodynamic instability, such as profound hypoxia and multiorgan failure, necessitating assertive early interventions to avert catastrophic consequences. The existing data on the utilization of mechanical circulatory support (MCS) devices are not exhaustive. Various options for percutaneous MCS devices exist, each possessing distinct advantages and disadvantages. There is an imminent imperative to develop a tailored approach for this high-risk patient cohort to enhance their overall outcomes.

Cannulation Strategies in Type A Aortic Dissection: Overlooked Details and Novel Approaches.

Aortic dissection type A is a life-threatening condition that frequently necessitates surgical intervention. This review focuses on central aortic cannulation, arch branch vessel (ABV) cannulation, and proximal arch cannulation as key techniques during aortic surgery. It discusses innovative solutions for addressing these challenges. The review synthesizes findings from recent studies and emphasizes the significance of meticulous planning and execution of cannulation in aortic dissection repair. This review aims to contribute to the advancement of surgical practices and the enhancement of patient outcomes in the management of type A aortic dissection (AAD) by addressing these frequently overlooked details.

Advancements in Myocardial Infarction Management: Exploring Novel Approaches and Strategies.

In the landscape of healthcare, the management of myocardial infarction (MI) stands as a pivotal challenge and a critical juncture where advancements are reshaping the trajectory of patient care. Myocardial infarction, commonly known as a heart attack, remains a foremost contributor to global morbidity and mortality. Conventional management strategies have historically focused on rapid restoration of blood flow through revascularization techniques. However, the last decade has witnessed a profound transformation, with a burgeoning emphasis on precision medicine and innovative interventions. This contextual backdrop sets the stage for a deep dive into the realm of novel diagnostic modalities, spanning high-sensitivity biomarkers, advanced imaging techniques, and data-driven algorithms. These innovations facilitate not only early detection but also the stratification of patients, paving the way for individualized treatment plans. By targeting the underlying mechanisms of myocardial damage, these interventions hold the promise of attenuating the impact of MI and promoting cardiac regeneration. It examines the integration of telemedicine, wearable devices, and remote monitoring platforms, bridging the gap between patients and caregivers while enabling timely interventions. Additionally, the psychosocial aspects of MI recovery are explored, highlighting the integration of psychological support and lifestyle interventions to enhance long-term well-being. By exploring novel diagnostics, innovative therapies, and holistic patient-centered strategies, it underscores the collaborative efforts of medical practitioners, researchers, and technological pioneers in reshaping the trajectory of MI care. As we stand at the intersection of medical advancement and compassionate patient management, embracing these novel approaches promises a future where the impact of myocardial infarction can be mitigated, and lives can be extended and enriched.

Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial.

OBJECTIVES: This study sought to prospectively evaluate the safety and efficacy of the Indigo aspiration system in submassive acute pulmonary embolism (PE). BACKGROUND: PE treatment with thrombolytics has bleeding risks. Aspiration thrombectomy can remove thrombus without thrombolytics, but data are lacking. METHODS: This study was a prospective, single-arm, multicenter study that enrolled patients with symptomatic acute PE ≤14 days, systolic blood pressure ≥90 mm Hg, and right ventricular-to-left ventricular (RV/LV) ratio >0.9. The primary efficacy endpoint was change in RV/LV ratio from baseline to 48 h post-procedure on core lab-adjudicated computed tomography angiography. The primary safety endpoint was a composite of 48-h major adverse events: device-related death, major bleeding, and device-related serious adverse events (clinical deterioration, pulmonary vascular, or cardiac injury). All sites received Institutional Review Board approval. RESULTS: A total of 119 patients (mean age 59.8 ± 15.0 years) were enrolled at 22 U.S. sites between November 2017 and March 2019. Median device insertion to removal time was 37.0 (interquartile range: 23.5 to 60.0) min. Two (1.7%) patients received intraprocedural thrombolytics. Mean RV/LV ratio reduction from baseline to 48 h post-procedure was 0.43 (95% confidence interval: 0.38 to 0.47; p < 0.0001). Two (1.7%) patients experienced 3 major adverse events. Rates of cardiac injury, pulmonary vascular injury, clinical deterioration, major bleeding, and device-related death at 48 h were 0%, 1.7%, 1.7%, 1.7%, and 0.8%, respectively. CONCLUSIONS: In this prospective, multicenter study the Indigo aspiration system was associated with a significant reduction in the RV/LV ratio and a low major adverse event rate in submassive PE patients. Intraprocedural thrombolytic drugs were avoided in 98.3% of patients. (Evaluating the Safety and Efficacy of the Indigo aspiration system in Acute Pulmonary Embolism [EXTRACT-PE]; NCT03218566).

Deploying Mechanical Circulatory Support Via the Axillary Artery in Cardiogenic Shock and High-Risk Percutaneous Coronary Intervention.

We sought to study the feasibility of axillary artery as alternative access for mechanical circulatory support (MCS) in cardiogenic shock and high-risk percutaneous coronary intervention (HR-PCI) patients with severe occlusive peripheral artery disease (PAD). In patients with severe PAD, the iliofemoral artery may be so diseased preventing deployment of MCS, precluding the use of lifesaving therapy. In such circumstances, the axillary artery may be a viable access site. Records of all patients presenting with cardiogenic shock or HR-PCI requiring MCS through axillary artery access at our institution from January 2016 to September 2018 were examined. Demographics, clinical, procedural, and outcomes data were collected on all patients. A total of 48 patients presented with cardiogenic shock (60%) or HR-PCI (40%) requiring MCS via axillary artery due to prohibitive PAD (mean age 66 ± 11 years). Admission diagnoses were non-ST segment elevation myocardial infarction (38%), unstable angina (23%), ST segment elevation myocardial infarction (19%), and cardiac arrest (21%). Time from axillary access to activation of Impella was 11.9 ± 4 minutes. Four patients required concomitant Impella RP for right ventricular support due to biventricular cardiogenic shock. Twenty-two patients died before Impella was explanted due to multiorgan failure, stroke, and infection. None of the patients who died had vascular complications related to axillary access. Axillary artery appears to be a viable alternative access for large bore devices in patients with prohibitive PAD. As experience of the field with this approach grows, it may be the default access for deployment of large bore sheaths in the future.

Sex-related difference in the use of percutaneous left ventricular assist device in patients undergoing complex high-risk percutaneous coronary intervention: Insight from the cVAD registry.

OBJECTIVE: To assess the in-hospital and short-term outcome differences between males and females who underwent high-risk PCI with mechanical circulatory support (MCS). BACKGROUND: Sex differences have been noted in several percutaneous coronary intervention (PCI) series with females less likely to be referred for PCI due increased risk of adverse events. However, data on sex differences in utilization and outcomes of high-risk PCI with MCS is scarce. METHODS: Using the cVAD Registry, we identified 1,053 high-risk patients who underwent PCI with MCS using Impella 2.5 or Impella CP. Patients with cardiogenic shock were excluded. A total of 792 (75.21%) males and 261 (24.79%) females were included in the analysis with median follow-up of 81.5 days. RESULTS: Females were more likely to be African American, older (72.05 ± 11.66 vs. 68.87 ± 11.17, p < .001), have a higher prevalence of diabetes (59.30 vs. 49.04%, p = .005), renal insufficiency (35.41 vs. 27.39%, p = .018), and peripheral vascular disease (31.89 vs. 25.39%, p of .05). Women had a higher mean STS score (8.21 ± 8.21 vs. 5.04 ± 5.97, p < .001) and lower cardiac output on presentation (3.64 ± 1.30 vs. 4.63 ± 1.49, p < .001). Although women had more comorbidities, there was no difference in in-hospital mortality, stroke, MI or need for recurrent revascularization compared to males. Females were more likely to have multivessel revascularization than males. Ejection fraction improved in both males and females at the time of discharge (26.59 to 31.40% and 30.75 to 36.05%, respectively, p < .0001). However, females had higher rate of bleeding requiring transfusion compared with males (9.58 vs. 5.30%, p = .019). CONCLUSION: Female patients undergoing high PCI were older and had more comorbidities but had similar outcomes compared to males.

Treatment of a Child With Submassive Pulmonary Embolism Associated With Hereditary Spherocytosis Using Ultrasound-Assisted Catheter-Directed Thrombolysis.

Background: The clinical presentation of hereditary spherocytosis varies from no symptoms to severe hemolytic anemia requiring splenectomy. Splenectomy imposes the risk of hypercoagulability and acute pulmonary embolism. Catheter-directed thrombolysis is an established treatment for submassive pulmonary embolism in adults. However, the literature regarding its use in children is limited. Case Report: We present the case of a 12-year-old male with hereditary spherocytosis who was diagnosed with pulmonary embolism and successfully treated with catheter-directed thrombolysis. The patient was initially treated with 10.5 mg of recombinant tissue plasminogen activator (r-tPA) delivered over 8 hours. However, because of minimal clinical and hemodynamic improvement, a second course of thrombolytic was administered for an additional 24 hours (25 mg of r-tPA), and the treatment resulted in marked clinical and hemodynamic improvement. Clot resolution was confirmed via angiography. The patient was discharged on enoxaparin and with regular follow-up. One year later, the patient was asymptomatic on enoxaparin. Conclusion: This case demonstrates that catheter-based treatment of submassive pulmonary embolism restores hemodynamic stability and thus is an alternative to surgery or systemic thrombolysis, even in the pediatric setting. While catheter-directed thrombolysis is a safe and effective alternative to systemic thrombolysis, further research is needed to establish appropriate dosing and indications in the adolescent population.

Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium.

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients.

Axillary Artery Access for Mechanical Circulatory Support Devices in Patients With Prohibitive Peripheral Arterial Disease Presenting With Cardiogenic Shock.

In patients with severe peripheral vascular disease, the common femoral artery may be so diseased as to not allow for deployment of mechanical circulatory support (MCS) such as in the setting of cardiogenic shock (CS). We sought to study the feasibility of axillary artery as alternative access for MCS in CS patients with severe occlusive peripheral artery disease (PAD). Records of all patients who presented with CS requiring MCS through axillary artery access from January 2016 to October 2017 were examined. Demographics, clinical, procedural, and outcomes data were collected on all patients. A total of 17 patients (mean age 68 ± 14years, 95% men) were identified. This was due to severe PAD in the iliac and/or common femoral arteries prohibiting large bore sheath access in allcases. Of the 17 patients, 9 required percutaneous coronary intervention. Time from axillary access to activation of Impella was 14.8 ± 4 minutes. Three patients required concomitant Impella RP for right ventricular support due to biventricular CS. Twelve patients died before Impella was explanted due to multiorgan failure, stroke, and infection. None of the patients who died had vascular complications related to axillary access. All 5 patients who survived to Impella explant were discharged from the hospital without major complication. Axillary artery is a safe and feasible alternative access for large bore devices in patients with prohibitive PAD. The meticulous technique described assures a very low rate of access related complications.

Large bore occlusive sheath management.

The field of interventional cardiology has evolved in its ability to carry out complex procedures. Procedures such as transcatheter aortic valve replacement (TAVR), endovascular aneurysm repair (EVAR), and mechanical circulatory support (MCS) devices require large bore access for successful deployment. With the use of large bore-access, comes with it an increased risk for vascular complications, such as thrombosis and limb ischemia. It is paramount for the interventional cardiologist to know how to manage such complications. In this manuscript, we describe our strategies for the management of occlusive sheaths increasingly encountered with large bore accesses in the upper and lower extremities. Strategies such as peeling away of the introducer sheath and the creation of internal and external bypass circuits are described. By using the described techniques, one can provide prolonged hemodynamic support and maintain large bore sheath access, without jeopardizing perfusion to the extremity.

Impact and Outcomes of Patients with Congestive Heart Failure Complicating Non-ST-Segment Elevation Myocardial Infarction,Results from a Nationally-Representative United States Cohort.

INTRODUCTION: Congestive heart failure (CHF) is seen in up to 13-25% of patients with NSTEMI. Recent data describing the impact of congestive heart failure (CHF) on in-hospital outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) in the United States is limited. We sought to examine the in-hospital outcomes, and management of CHF in patients admitted to the hospital with NSTEMI. METHODS: National Inpatient Sample (NIS) database (2010-2014) was analyzed to identify patients with NSTEMI using ICD-9-CM codes. The primary outcome was in-hospital mortality. Propensity score-matching analysis compared mortality in CHF patients to matched controls without CHF. RESULTS: Of 247,624 patients with NSTEMI, 84,115 (34%) had CHF. Patients with CHF were less likely to receive percutaneous coronary intervention (PCI) [20.48% vs. 40.9%, P < 0.001] or coronary artery bypass grafting (CABG) [8.2% vs 9.6%, P < 0.001] during hospitalization. Also, they had longer lengths of stay and higher risk for in-hospital adverse outcomes. CHF was the strongest predictor of in-hospital death. The increased mortality risk was persistent after propensity matching (RR 1.27; 95% CI 1.22 to 1.33). CONCLUSION: CHF among patients with NSTEMI is associated with increased risk for in-hospital mortality and adverse outcomes.

Clinical impact of advanced chronic kidney disease on outcomes and in-hospital complications of Takotsubo Syndrome (broken-heart-syndrome): Propensity-matched national study.

Multiple studies evaluated the outcomes and complications rate of Takotsubo Syndrome (TTS) in patients with and without advanced chronic kidney disease (CKD), revealed conflicting results. This study aims to assess the clinical outcomes and impact of advanced CKD on patients hospitalized with Takotsubo Syndrome. Patients who presented with Takotsubo cardiomyopathy between 2010 and 2014 were identified in the National Inpatient Sample (NIS) database using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), and subsequently were divided into two groups, with advanced CKD and without advanced CKD. NIS is the largest all-payer inpatient stays database in the United States. The primary outcome was the effect of advanced CKD on inpatient mortality in comparison to the non-advanced CKD group. Secondary outcomes were the impact of CKD on TTS in-hospital complications. We also evaluated the length of hospital stay and the cost of hospitalization. Propensity score-matched analysis was performed to address potential confounding. The advanced CKD group had no significant increase in the risk of In-hospital mortality (OR 0.99; 95% CI 0.75-1.31, P = 0.269). However, advanced CKD patients were more likely to develop acute kidney injury (AKI) requiring dialysis (OR: 5.12, 95% CI: 3.16-8.30, P = <0.0001), and were more likely to stay longer at the hospital (OR 1.12; 95% CI 1.03 to 1.22, P 0.010). In conclusion, advanced chronic kidney disease does not increase immediate in-hospital mortality, neither most of the TTS in-hospital complications, apart from AKI and hospital length of stay, in comparison to the patients with non-advanced CKD.

In-hospital outcomes of transcatheter mitral valve repair with Mitraclip in patients with pulmonary hypertension: Insights from the National Inpatient Sample.

BACKGROUND: Periprocedural outcomes of transcatheter mitral valve repair (TMVR) with Mitraclip in patients with pulmonary hypertension (PH) are not well studied. METHODS: Patients who underwent TMVR with Mitraclip between 2011 and 2015 were identified using the National Inpatient Sample (NIS). All missing variables were excluded from the analysis and therefore, complete case analysis was performed. RESULTS: A total of 1,037 patients underwent TMVR with Mitraclip between 2011 and 2015. The prevalence of PH in these patients was 32.6%. In-hospital outcomes were compared between PH group and non-PH group. Inpatient mortality after TMVR was similar between the two groups (3.2% vs. 2.1%, OR 1.57, P = 0.335). There was no statistical significance between the two groups in the rates of hemorrhage requiring transfusion (8.5% vs. 7.2%, OR 1.17, P = 0.587), cardiogenic shock (4.4% vs. 4.5%, OR 0.98, P = 0.951), acute respiratory failure (15.2% vs. 13.1%, OR 1.23, P = 0.460), postoperative sepsis (2.75% vs. 3.9%, OR 0.66, P = 0.340), postoperative deep vein thrombosis or pulmonary embolism (2.7% vs. 3.9%, OR 1.98, P = 0.348). In addition, non-routine home discharge, median hospital cost and length of stay were similar between the two groups. CONCLUSION: Pre-existing PH in patients undergoing TMVR with Mitraclip does not adversely affect in-hospital outcomes in this cohort of patients. Therefore, PH does not carry a prohibitive risk in selecting patients for Mitraclip procedure.

Catheter-directed therapy for acute pulmonary embolism in children.

BACKGROUND: Acute pulmonary embolism is a life-threatening condition and rarely occurs in children. In adults, catheter-directed therapy emerges as a potentially safer and effective therapeutic option. However, there is a paucity of data on the safety and efficacy of catheter-directed therapy for pulmonary embolism in children. We report a single-centred experience of catheter-directed therapy for acute pulmonary embolism in children. METHODS: This is a retrospective study of children who had no CHD and underwent catheter-directed therapy at Detroit Medical Center during a 12-year period from 2005 to 2017. Demographic and clinical data associated with pulmonary embolism were collected along with the outcome. RESULTS: A total of nine patients of median age 16 years with the range from 12 to 20 received catheter-directed therapy for sub-massive (n = 6) and massive pulmonary embolism (n = 3). Among nine patients, one patient received Angiojet thrombectomy and balloon angioplasty, whereas eight patients received catheter-directed thrombolysis using tissue plasminogen activator through infusion catheters (n = 3) or EkoSonic ultrasound-accelerated thrombolysis system (n = 5). In four out of five patients treated with EkoSonic, significant clinical improvement was noticed within 24 hours. Among seven patients who survived, two patients had minor gastrointestinal bleeding with median hospital stay of 8 days with the range from 5 to 24 days, and two patients with massive pulmonary embolism died possibly due to delayed institution of catheter-directed therapy. CONCLUSION: Catheter-directed therapy with/without EkoSonic is an emerging alternative therapy for sub-massive and massive pulmonary embolism in children. A timely institution of catheter-directed therapy appeared important to improve the outcome.

The impact of atrial fibrillation on transcatheter mitral valve repair outcomes: A propensity-matched analysis.

BACKGROUND: The concomitant presence of atrial fibrillation (AF) in the setting of Transcatheter Mitral Valve Repair (TMVR) represents a clinical challenge. Despite the high AF burden in patients presenting for the TMVR procedure, there are no studies that evaluate the impact of AF on in-hospital outcomes of TMVR in a nationally representative United States sample reflecting real practice. Therefore, we sought to study the outcomes of AF patients undergoing TMVR. METHODS AND RESULTS: The study included 1026 patients from the National Inpatient Sample (NIS) registry. Patients (age ≥18 years) who had undergone TAVR as a primary procedure from 2011 to 2014 were included, using the ICD-9-CM diagnostic codes. We examined patient characteristics and in-hospital outcomes. To account for patient and hospital-level baseline differences, we performed propensity score-matched analysis. The prevalence of AF was approximately 56%. After adjusting for patient-level and hospital-level characteristics, there was no statistical difference regarding in-hospital mortality (odds ratio [OR] 0.72, 95%CI 0.29-1.80, P = 0.487), post-TMVR complications, length of stay (OR 1.15, 95%CI 0.97-1.38, P = 0.111), and cost of hospitalization (OR 1.04, 95%CI 0.94-1.14, P = 0.475) between the group with AF versus without AF. However, patients with AF were more likely to have non-routine hospital discharge (42.94% vs 35.48% P = 0.02). CONCLUSION: AF is a frequently encountered arrhythmia among patients undergoing TMVR with MitraClip. However, TMVR can be performed safely in the vast majority of patients, irrespective of their baseline rhythm.

Access and closure management of large bore femoral arterial access.

Femoral and radial artery access continue to be the standard of care for percutaneous coronary interventions. Cardiac catheterization has progressed to encompass a wide range of diagnostic and interventional procedures including coronary, peripheral, endovascular, and structural heart disease interventions. Despite advanced technology to make these procedures safe, bleeding, and vascular complications continue to be a substantial source of morbidity, especially in patients undergoing large-bore access procedures. New variations of percutaneous devices have reduced complications associated with these procedures. However, safe vascular access with effective hemostasis requires special techniques which have not been well described in the literature. Large-bore femoral artery access is feasible, safe, and associated with low complication rates when a protocol is implemented. Wayne State University, Detroit Medical Center Heart Hospital is a tertiary care, high-volume center for endovascular, structural heart and complex high risk indicated procedures with more 150 procedures involving mechanical circulatory support (MCS) devices per year. In this manuscript, we describe our approach to femoral artery large-bore sheath insertion and management. Our protocol includes proper identification of the puncture site, device selection, insertion, assessment of limb perfusion while on prolong MCS support, and hemostasis techniques after sheath removal.

Impella RP Support and Catheter-Directed Thrombolysis to Treat Right Ventricular Failure Caused by Pulmonary Embolism in 2 Patients.

Right ventricular failure secondary to pulmonary embolism is associated with morbidity and death. The Impella RP System has often been used for percutaneous mechanical circulatory support in patients with right ventricular failure from other causes, including myocardial infarction, cardiac surgery, and left ventricular assist device implantation. We report 2 cases of massive pulmonary embolism in which combined Impella RP use and ultrasound-assisted catheter-directed thrombolysis effectively treated shock caused by right ventricular failure and contributed to successful outcomes. To our knowledge, only one other patient with this indication had been treated with the Impella RP device.

Outcomes and Effects of Hepatic Cirrhosis in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Comparative outcomes of transcatheter aortic valve implantation (TAVI) in patients with and without liver cirrhosis are scarce. This study aimed to assess the clinical outcomes and impact of liver cirrhosis on patients who underwent TAVI. Patient with liver cirrhosis who underwent TAVI 2011 to 2014 were identified in the National Inpatient Sample database using the International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM). The primary outcome was the effect of liver cirrhosis on inpatient mortality. Secondary outcomes were the impact of liver cirrhosis on post-TAVI complications. We also evaluated the length of hospital stay and the cost of hospitalization. Propensity score-matched analysis was performed to address potential confounding. The cirrhotic patients who underwent TAVI had no significant increase in the risk of in-hospital mortality (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.59 to 2.10, p = 0.734) or after procedural complications. Furthermore, cirrhotic patients were less likely to develop vascular complications requiring surgery (OR 0.47, 95% CI 0.23 to 0.98, p = 0.043), to develop after procedural deep vein thrombosis(OR <0.00, 95% CI <0.001 to <0.0001, p <0.0001), and to require pacemaker implantation. However, cirrhotic patients were more likely to undergo nonroutine hospital discharges (OR 1.50, 95% CI 1.15 to 1.96, p = 0.003). In conclusion, TAVI is a safe and reasonable therapeutic option for cirrhotic patients with severe aortic stenosis, requiring aortic valve replacement.

A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial.

OBJECTIVES: The aim of this study was to determine the lowest optimal tissue plasminogen activator (tPA) dose and delivery duration using ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk (submassive) pulmonary embolism. BACKGROUND: Previous trials of USCDT used tPA over 12 to 24 h at doses of 20 to 24 mg for acute pulmonary embolism. METHODS: Hemodynamically stable adults with acute intermediate-risk pulmonary embolism documented by computed tomographic angiography were randomized into this prospective multicenter, parallel-group trial. Patients received treatment with 1 of 4 USCDT regimens. The tPA dose ranged from 4 to 12 mg per lung and infusion duration from 2 to 6 h. The primary efficacy endpoint was reduction in right ventricular-to-left ventricular diameter ratio by computed tomographic angiography. A major secondary endpoint was embolic burden by refined modified Miller score, measured on computed tomographic angiography 48 h after initiation of USCDT. RESULTS: One hundred one patients were randomized, and improvements in right ventricular-to-left ventricular diameter ratio were as follows: arm 1 (4 mg/lung/2 h), 0.40 (24%; p = 0.0001); arm 2 (4 mg/lung/4 h), 0.35 (22.6%; p = 0.0001); arm 3 (6 mg/lung/6 h), 0.42 (26.3%; p = 0.0001); and arm 4 (12 mg/lung/6 h), 0.48 (25.5%; p = 0.0001). Improvement in refined modified Miller score was also seen in all groups. Four patients experienced major bleeding (4%). Of 2 intracranial hemorrhage events, 1 was attributed to tPA delivered by USCDT. CONCLUSIONS: Treatment with USCDT using a shorter delivery duration and lower-dose tPA was associated with improved right ventricular function and reduced clot burden compared with baseline. The major bleeding rate was low, but 1 intracranial hemorrhage event due to tPA delivered by USCDT did occur.