Modern Treatment of Pulmonary Embolism (USCDT vs MT): Results From a Real-World, Big Data Analysis (REAL-PE).

Background: Advanced therapies are increasingly utilized to treat pulmonary embolism (PE). A unique data platform allows access to electronic health record data for comparison of the safety of PE therapies. Methods: All data from Truveta (Truveta, Inc) were analyzed (16 systems, 83,612,413 patients, 535,567 with PE). All patients treated with ultrasound-assisted catheter-directed thrombolysis (USCDT) (Boston Scientific) or mechanical thrombectomy (MT) (Inari Medical) for PE were identified. The primary analysis was based on index procedures performed from January 2009 to May 2023, and contemporary analysis on those performed from January 2018 to May 2023. Bleeding was assessed via direct laboratory analysis and transfusion administration documentation. International Society for Thrombosis and Hemostasis (ISTH) and Bleeding Academic Research Consortium (BARC) 3b definitions were recreated. Multiple logistic regression analysis of major bleeding was performed. In-hospital death and median length of stay were measured. Results: For the primary analysis, 2259 patients (N = 1577 USCDT, N = 682 MT) and for the contemporary analysis 1798 patients (N = 1137 USCDT, N = 661 MT) met the criteria. Incidence of hemoglobin reduction (>2 and >5 g/dL) and transfusions received were significantly higher among MT-treated patients in both analyses, as was ISTH and BARC 3b major bleeding (primary: ISTH MT 17.3% vs USCDT 12.4% P = .002; BARC 3b MT 15.4% vs USCDT 11.8% P = .019) (contemporary: ISTH MT 17.2% vs USCDT 11.0% P = .0002; BARC 3b MT 15.4% vs USCDT 10.6% P = .002). Regression analysis demonstrated that MT is associated with major bleeding. Median length of stay, all-cause 30-day readmission and in-hospital mortality were similar between groups. Intracranial hemorrhage was more common with MT. Conclusions: Major bleeding derived from direct laboratory and transfusion data occurred more frequently with MT vs USCDT. Intracranial hemorrhage was more common among MT-treated patients. In the absence of randomized data, these results provide guidance regarding the bleeding risk and safety of strategies for advanced PE therapy.

Clinical Outcomes of Non-Stent-Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry.

For endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent-based balloon angioplasty (percutaneous transluminal angioplasty) and adjunctive treatments with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. A total of 1,060 patients from the multicenter XLPAD registry who underwent non-stent-based BTK PAD intervention between 2006 and 2021 were included. The primary outcome was the 1-year incidence of major adverse limb events (MALEs), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. A total of 566 patients underwent BTK and 494 BTK + FP interventions; 72% were men, with a mean age of 68.4 ± 10.9 years. Diabetes mellitus was more prevalent in the BTK-only group (76.5% vs 69%, p = 0.006). Mean Rutherford class was 4.2 ± 1.18; chronic limb-threatening ischemia was more frequent in the BTK group (55.3% vs 49%, p = 0.040). Moderate to severe calcification was more frequent in the BTK + FP group (21.2% vs 27.1%, p = 0.024), as was lesion length (110.6 ± 77.3 vs 135.4 ± 86.3 mm, p <0.001). Nearly 81% of lesions were treated with percutaneous transluminal angioplasty. Drug-coated balloon (1.6% vs 14%, p <0.001) and atherectomy (38% vs 58.5%, p <0.001) use was more frequent in the BTK + FP group. The rate of procedural success was higher in the BTK + FP group (86% vs 91%, p = 0.009), with amputation being the most common complication at 3.3% within 30 days after the procedure. The rates of 1-year MALE (21.2% vs 22.3%, p = 0.675) and mortality (4.6% vs 3.4%, p = 0.3) were similar between the BTK and BTK + FP groups. Nonstent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. Condensed Abstract: The vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal PAD in patients who undergo BTK interventions can affect the outcome of the procedure. This report explores immediate procedural success and major adverse limb events at 1 year after balloon angioplasty treatment for isolated BTK PAD and in patients who underwent an additional femoropopliteal PAD intervention.

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants.

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD. Fifty-eight patients completed walking performance testing and muscle biopsy before and 6 months after revascularization procedures. Muscle fiber morphology, desmin structure, and mitochondria respiration assessments before and after the revascularization were evaluated. Revascularization improved limb hemodynamics, walking function, and muscle morphology. Qualitatively not all participants recovered normal structural architecture of desmin in the myopathic myofibers after revascularization. Heterogenous responses in the recovery of desmin structure following revascularization may be caused by other underlying factors not reversed with hemodynamic improvements. Revascularization interventions clinically improve patient walking ability and can reverse the multiple subcellular functional and structural abnormalities in muscle cells. Further study is needed to characterize desmin structural remodeling with improvements in skeletal muscle morphology and function.

Sex in cardiovascular disease: Why this biological variable should be considered in in vitro models.

Cardiovascular disease (CVD), the world's leading cause of death, exhibits notable epidemiological, clinical, and pathophysiological differences between sexes. Many such differences can be linked back to cardiovascular sexual dimorphism, yet sex-specific in vitro models are still not the norm. A lack of sex reporting and apparent male bias raises the question of whether in vitro CVD models faithfully recapitulate the biology of intended treatment recipients. To ensure equitable treatment for the overlooked female patient population, sex as a biological variable (SABV) inclusion must become commonplace in CVD preclinical research. Here, we discuss the role of sex in CVD and underlying cardiovascular (patho)physiology. We review shortcomings in current SABV practices, describe the relevance of sex, and highlight emerging strategies for SABV inclusion in three major in vitro model types: primary cell, stem cell, and three-dimensional models. Last, we identify key barriers to inclusive design and suggest techniques for overcoming them.

Evidence-Based Update on Transcatheter Therapies for Pulmonary Embolism.

PURPOSE OF REVIEW: Pulmonary embolism (PE) remains a leading cause of cardiovascular morbidity and mortality. Multiple new therapies are in development and under study to improve our contemporary care of patients with PE. We review and compare here these novel therapeutics and technologies. RECENT FINDINGS: Multiple novel therapeutic devices have been developed and are under active study. This work has advanced the care of patients with intermediate and high-risk PE. Novel therapies are improving care of complex PE patients. These have inspired large multicenter international randomized controlled trials that are actively recruiting patients to advance the care of PE. These studies will work towards advancing guidelines for clinical care of patients with PE.

SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks.

With new daily discoveries about the long-term impacts of COVID-19, there is a clear need to develop in vitro models that can be used to better understand the pathogenicity and impact of COVID-19. Here, we demonstrate the utility of developing a model of endothelial dysfunction that utilizes human induced pluripotent stem cell-derived endothelial progenitors encapsulated in collagen hydrogels to study the effects of COVID-19 on the endothelium. These cells form capillary-like vasculature within 1 week after encapsulation and treating these cell-laden hydrogels with SARS-CoV-2 spike protein resulted in a significant decrease in the number of vessel-forming cells as well as vessel network connectivity quantified by our computational pipeline. This vascular dysfunction is a unique phenomenon observed upon treatment with SARS-CoV-2 SP and is not seen upon treatment with other coronaviruses, indicating that these effects were specific to SARS-CoV-2. We show that this vascular dysfunction is caused by an increase in inflammatory cytokines, associated with the COVID-19 cytokine storm, released from SARS-CoV-2 spike protein treated endothelial cells. Following treatment with the corticosteroid dexamethasone, we were able to prevent SARS-CoV-2 spike protein-induced endothelial dysfunction. Our results highlight the importance of understanding the interactions between SARS-CoV-2 spike protein and the endothelium and show that even in the absence of immune cells, the proposed 3D in vitro model for angiogenesis can reproduce COVID-19-induced endothelial dysfunction seen in clinical settings. This model represents a significant step in creating physiologically relevant disease models to further study the impact of long COVID and potentially identify mitigating therapeutics.

Outcomes of atherectomy in patients undergoing lower extremity revascularisation.

BACKGROUND: There is a paucity of real-world data on the in-hospital (IH) and post-discharge outcomes in patients undergoing lower extremity peripheral vascular intervention (PVI) with adjunctive atherectomy. AIMS: In this retrospective, registry-based study, we evaluated IH and post-discharge outcomes among patients undergoing PVI, treated with or without atherectomy, in the National Cardiovascular Data Registry PVI Registry. METHODS: The IH composite endpoint included procedural complications, bleeding or thrombosis. The primary out-of-hospital endpoint was major amputation at 1 year. Secondary endpoints included repeat endovascular or surgical revascularisation and death. Multivariable regression was used to identify predictors of atherectomy use and its association with clinical endpoints. RESULTS: A total of 30,847 patients underwent PVI from 2014 to 2019, including 10,971 (35.6%) treated with atherectomy. The unadjusted rate of the IH endpoint occurred in 524 (4.8%) of the procedures involving atherectomy and 1,041 (5.3%) of non-atherectomy procedures (p=0.07). After adjustment, the use of atherectomy was not associated with an increased risk of the combined IH endpoint (p=0.68). In the 6,889 (22.4%) patients with out-of-hospital data, atherectomy was associated with a reduced risk of amputation (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI]: 0.51-0.85; p<0.01) and surgical revascularisation (aHR 0.63, 95% CI: 0.44-0.89; p=0.017), no difference in death rates (p=0.10), but an increased risk of endovascular revascularisation (aHR 1.21, 95% CI: 1.06-1.39; p<0.01) at 1 year. CONCLUSIONS: The use of atherectomy during PVI is common and is not associated with an increase in IH adverse events. Longitudinally, patients treated with atherectomy undergo repeat endovascular reintervention more frequently but experience a reduced risk of amputation and surgical revascularisation.

Practical solutions for implementation of blood cholesterol guidelines in clinical practice.

Underutilization of lipid-lowering therapy (LLT) and failure to attain guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals are important quality gaps in cardiovascular risk optimization, especially among patients with atherosclerotic cardiovascular disease (ASCVD). Large database analyses demonstrate an unmet need for improved LDL-C measurement, and that nearly 75% of patients with ASCVD have an LDL-C level above guideline-recommended levels, and greater than 50% are not treated with statins or ezetimibe. Proposed solutions for overcoming these obstacles to optimal lipid management include provider- and patient-facing educational interventions, health information technology strategies, implementation of incentive-based care, advocacy efforts, and systems-based process innovations. While individual interventions may not be enough to overcome the totality of barriers to optimal LLT, comprehensive multifaceted approaches that address barriers at the provider, patient, and healthcare delivery level are likely to offer the greatest likelihood of success and improved patient outcomes.

SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks.

With new daily discoveries about the long-term impacts of COVID-19 there is a clear need to develop in vitro models that can be used to better understand the pathogenicity and impact of COVID-19. Here we demonstrate the utility of developing a model of endothelial dysfunction that utilizes induced pluripotent stem cell-derived endothelial progenitors encapsulated in collagen hydrogels to study the effects of COVID-19 on the endothelium. We found that treating these cell-laden hydrogels with SARS-CoV-2 spike protein resulted in a significant decrease in the number of vessel-forming cells as well as vessel network connectivity. Following treatment with the anti-inflammatory drug dexamethasone, we were able to prevent SARS-CoV-2 spike protein-induced endothelial dysfunction. In addition, we confirmed release of inflammatory cytokines associated with the COVID-19 cytokine storm. In conclusion, we have demonstrated that even in the absence of immune cells, we are able to use this 3D in vitro model for angiogenesis to reproduce COVID-19 induced endothelial dysfunction seen in clinical settings.

Endovascular Treatment and Outcomes for Femoropopliteal In-Stent Restenosis: Insights from the XLPAD Registry.

Background: There is limited "real-world" evidence examining treatment modalities and outcomes in patients with symptomatic peripheral arterial disease undergoing endovascular treatment of femoropopliteal (FP) in-stent restenosis (ISR). Materials and Methods: We compared outcomes in 2,895 patients from the XLPAD registry (NCT01904851) between 2006 and 2019 treated for FP ISR (n = 347) and non-ISR (n = 2,548) lesions. Primary endpoint included major adverse limb events (MALE) at 1 year, a composite of all-cause death, target limb repeat revascularization, or major amputation. Results: ISR patients were more frequently on antiplatelet (94.5% vs 89.4%, p=0.007) and statin (68.9% vs 60.3%, p=0.003) therapies. Lesion length was similar (ISR: 145 ± 99 mm vs. non-ISR: 142 ± 99 mm, p=0.55). Fewer treated ISR lesions were chronic total occlusions (47.3% vs. 53.7%, p=0.02) and severely calcified (22.4% vs. 44.7%, p < 0.001). Atherectomy (63.5% vs. 45.0%, p < 0.001) and drug-coated balloons (DCB; 4.7% vs. 1.7%, p < 0.001) were more frequently used in ISR lesions. The distal embolization rate was higher in ISR lesions (2.4% vs. 0.9%, p=0.02). Repeat revascularization (21.5% vs. 16.7%, p=0.04; Figure) was higher and freedom from MALE at 1 year was significantly lower (87% vs. 92.5%, p < 0.001) in the ISR group. Conclusion: Atherectomy and DCB are more frequently used to treat FP ISR lesions. Patients with FP ISR have more intraprocedural distal embolization, higher repeat revascularization procedures, and lower freedom from MALE at 1 year.

Safety and Efficacy of Ultra Short-duration Dual Antiplatelet Therapy After Percutaneous Coronary Interventions: A Meta-analysis of Randomized Controlled Trials.

Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention (PCI) to reduce stent thrombosis, but DAPT increases bleeding risks. The optimal duration of DAPT that provides the maximum protective ischemic effect along with the minimum bleeding risk is unclear. This is the first meta-analysis comparing outcomes for 1-month versus longer DAPT strategies following PCI.We searched PubMed, Cochrane, and ClinicalTrials.gov databases (from inception to October 2021) for randomized controlled trials that compared 1-month duration vs > 1-month duration of DAPT following PCI. We used a random-effects model to calculate risk ratio (RR) with 95% confidence interval (CI). The co-primary outcomes for study selection were all-cause mortality, major bleeding, and stent thrombosis. Secondary outcomes included myocardial infarction (MI), cardiovascular mortality, ischemic stroke and target vessel revascularization. A total of five randomized controlled trials were included [n = 29,355; 1-month DAPT(n = 14,662) vs > 1-month DAPT (n = 14,693)]. There was no statistically significant difference between the two groups in terms of all-cause mortality (RR 0.89; 95% CI 0.78-1.03; P = 0.12) and stent thrombosis (RR 1.07; 95% CI 0.80-1.43; P = 0.65). Similarly, there were no significant differences in MI, cardiovascular mortality, ischemic stroke, and target vessel revascularization. The rate of major bleeding was significantly lower in the group treated with DAPT for 1-month (RR 0.74; 95% CI 0.56-0.99, P = 0.04).There is no difference in all-cause mortality, cardiovascular mortality, MI, stent thrombosis, ischemic stroke, and target vessel revascularization with 1-month of DAPT following PCI with contemporary drug eluting stents compared to longer DAPT duration.

ACGME Interventional Cardiology Milestones 2.0-an overview: Endorsed by the Accreditation Council for Graduate Medical Education.

This document provides an overview of the rationale, development, interpretation, and practical suggestions for implementation of the new Accreditation Council for Graduate Medical Education (ACGME) Interventional Cardiology (IC) Milestones 2.0. Previously, IC programs used the general ACGME Milestones for internal medicine. The IC Milestones version 2.0 updates the ACGME competencies to be specific to training in IC. In 2019 an ACGME working group consisting of IC program directors, a lay representative, and representatives from the American Board of Internal Medicine met to develop the IC Milestones version 2.0. The ACGME IC Milestones 2.0 establishes a framework for formative feedback for trainees within domains of patient care, medical knowledge, systems-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills. The 2021 IC Milestones 2.0 provides a framework for IC mentors and trainees to identify areas for improvement or commendation help stimulate meaningful educational discussions, and provide the basis for self-reflection and self-improvement.

Differences Between Patients With Intermittent Claudication and Critical Limb Ischemia Undergoing Endovascular Intervention: Insights From the Excellence in Peripheral Artery Disease Registry.

BACKGROUND: There are limited data on differences in angiographic distribution of peripheral artery disease and endovascular revascularization strategies in patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). We aimed to compare anatomic features, treatment strategies, and clinical outcomes between patients with IC and CLI undergoing endovascular revascularization. METHODS: We examined 3326 patients enrolled in the Excellence in Peripheral Artery Disease registry from 2006 to 2019 who were referred for endovascular intervention for IC (n=1983) or CLI (n=1343). The primary outcome was 1-year major adverse limb events, which included death, repeat target limb revascularization, or target limb amputation. RESULTS: Patients with CLI were older and more likely to have diabetes and chronic kidney disease and less likely to receive optimal medical therapy compared with IC. Patients with IC had higher femoropopliteal artery interventions (IC 87% versus CLI 65%; P<0.001), while below the knee interventions were more frequent in CLI (CLI 47% versus IC 12%; P<0.001). Patients with CLI were more likely to have multilevel peripheral artery disease (CLI 32% versus IC 15%, P<0.001). Patients with IC were predominantly revascularized with stents (IC 48% versus CLI 37%; P<0.001) while balloon angioplasty was more frequent in CLI (CLI 37% versus IC 25%; P<0.001). All-cause mortality was higher in patients with CLI (CLI 4% versus IC 2%; P=0.014). Major adverse limb event rates for patients with IC and CLI were 16% and 26%, respectively (P<0.001) and remained higher in CLI after multivariable adjustment of baseline risk factors. CONCLUSIONS: Patients with IC and CLI have significant anatomic, lesion, and treatment differences with significantly higher mortality and adverse limb outcomes in CLI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01904851. Graphic Abstract: A graphic abstract is available for this article.