Transcatheter aortic valve replacement achieves similar predicted effective orifice area to surgical aortic valve replacement in bicuspid aortic stenosis.

BACKGROUND: Studies comparing transcatheter and surgical aortic valve replacement (TAVR and SAVR) for patients with trileaflet aortic stenosis (AS) have found similar or larger effective orifice area (EOA) for TAVR prostheses. To our knowledge, no studies have compared EOA in patients undergoing TAVR versus SAVR for bicuspid AS. METHODS: We retrospectively compared prosthetic valvular sizing and predicted EOA for patients with bicuspid AS undergoing TAVR or SAVR at our institution between January 1, 2016, and December 31, 2021. We excluded patients undergoing procedures for indications other than AS and those without a pre-procedural gated Chest CT. Comparisons included demographics, comorbidities, annular size, prosthetic valve size, predicted EOA and prosthesis-patient mismatch (PPM) for TAVR (N = 78) and SAVR (N = 74) cohorts. RESULTS: TAVR patients had smaller pre-procedural annular area (501.7 mm2 vs. 571.8 mm2, p < 0.05) and annular perimeter (80.6 mm vs. 86.5 mm, p < 0.05), but larger mean implanted prosthetic valve size (26.4 mm vs 24.2 mm, p < 0.001) compared to SAVR patients. No differences were observed in predicted EOA, predicted EOA indexed to patient body surface area (EOAi), or predicted PPM grade between TAVR and SAVR groups, including in cohorts sorted by pre-procedural annular size. CONCLUSIONS: For bicuspid AS patients undergoing aortic valve replacement, TAVR achieves similar predicted EOA to SAVR. These data support the use of TAVR in selected patients with bicuspid AS and can inform heart team discussions.

Contemporary Management and Outcomes of Patients With High-Risk Pulmonary Embolism.

BACKGROUND: Contemporary care patterns/outcomes in high-risk pulmonary embolism (PE) patients are unknown. OBJECTIVES: This study sought to characterize the management of high-risk PE patients and identify factors associated with poor outcomes. METHODS: A retrospective analysis of the PERT (Pulmonary Embolism Response Team) Consortium Registry was performed. Patients presenting with intermediate-risk PE, high-risk PE, and catastrophic PE (those with hemodynamic collapse) were identified. Patient characteristics were compared with chi-square testing for categorical covariates and Student's t-test for continuous covariates. Multivariable logistic regression was used to assess associations between clinical characteristics and outcomes in the high-risk population. RESULTS: Of 5,790 registry patients, 2,976 presented with intermediate-risk PE and 1,442 with high-risk PE. High-risk PE patients were more frequently treated with advanced therapies than intermediate-risk PE patients (41.9% vs 30.2%; P < 0.001). In-hospital mortality (20.6% vs 3.7%; P < 0.001) and major bleeding (10.5% vs. 3.5%; P < 0.001) were more common in high-risk PE. Multivariable regression analysis demonstrated vasopressor use (OR: 4.56; 95% CI: 3.27-6.38; P < 0.01), extracorporeal membrane oxygenation use (OR: 2.86; 95% CI: 1.12-7.30; P = 0.03), identified clot-in-transit (OR: 2.26; 95% CI: 1.13-4.52; P = 0.02), and malignancy (OR: = 1.70; 95% CI: 1.13-2.56; P = 0.01) as factors associated with in-hospital mortality. Catastrophic PE patients (n = 197 [13.7% of high-risk PE patients]) had higher in-hospital mortality (42.1% vs 17.2%; P < 0.001) than those presenting with noncatastrophic high-risk PE. Extracorporeal membrane oxygenation (13.3% vs. 4.8% P < 0.001) and systemic thrombolysis (25% vs 11.3%; P < 0.001) were used more commonly in catastrophic PE. CONCLUSIONS: In the largest analysis of high-risk PE patients to date, mortality rates were high with the worst outcomes among patients with hemodynamic collapse.

Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications.

BACKGROUND: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. OBJECTIVES: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications. METHODS: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis. RESULTS: The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients. CONCLUSIONS: There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775).

Advanced Treatment of Hemodynamically Unstable Acute Pulmonary Embolism and Clinical Follow-up.

High-risk acute pulmonary embolism (PE), defined as acute PE associated with hemodynamic instability, remains a significant contributor to cardiovascular morbidity and mortality in the United States and worldwide. Historically, anticoagulant therapy in addition to systemic thrombolysis has been the mainstays of medical therapy for the majority of patients with high-risk PE. In efforts to reduce the morbidity and mortality, a wide array of interventional and surgical therapies has been developed and employed in the management of these patients. However, the most recent guidelines for the management of PE have reserved the use of these advanced therapies in scenarios where thrombolytic therapy plus anticoagulation are unsuccessful. This is due largely to the lack of prospective, randomized studies in this population. Stemming from this, the approach to treatment of these patients varies widely depending on institutional experience and resources. Furthermore, morbidity and mortality remain unacceptably high in this population, with estimated 30-day mortality of at least 30%. As such, development of a standardized approach to treatment of these patients is paramount to improving outcomes. Early and accurate risk stratification in conjunction with a multidisciplinary team approach in the form of a PE response team is crucial. With the advent of novel therapies for the treatment of acute PE, in addition to the growing availability of and familiarity with mechanical circulatory support systems, such a standardized approach may now be within reach.

Racial Differences in Presentation and Outcomes After Peripheral Arterial Interventions: Insights From the NCDR-PVI Registry.

BACKGROUND: We assess the rates of device use and outcomes by race among patients undergoing lower extremity peripheral arterial intervention using the American College of Cardiology National Cardiovascular Data Registry-Peripheral Vascular Intervention (PVI) registry. METHODS: Patients who underwent PVI between April 2014 and March 2019 were included. Socioeconomic status was evaluated using the Distressed Community Index score for patients' zip codes. Multivariable logistic regression was used to assess factors associated with utilization of drug-eluting technologies, intravascular imaging, and atherectomy. Among patients with Centers for Medicare and Medicaid Services data, we compared 1-year mortality, rates of amputation, and repeat revascularizations. RESULTS: Of 63 150 study cases, 55 719 (88.2%) were performed in White patients and 7431 (11.8%) in Black patients. Black patients were younger (67.9 versus 70.0 years), had higher rates of hypertension (94.4% versus 89.5%), diabetes (63.0% versus 46.2%), less likely to be able to walk 200 m (29.1% versus 24.8%), and higher Distressed Community Index scores (65.1 versus 50.6). Black patients were provided drug-eluting technologies at a higher rate (adjusted odds ratio, 1.14 [95% CI, 1.06-1.23]) with no difference in atherectomy (adjusted odds ratio, 0.98 [95% CI, 0.91-1.05]) or intravascular imaging (adjusted odds ratio, 1.03 [95% CI, 0.88-1.22]) use. Black patients experienced a lower rate of acute kidney injury (adjusted odds ratio, 0.79 [95% CI, 0.72-0.88]). In Centers for Medicare and Medicaid Services-linked analyses of 7429 cases (11.8%), Black patients were significantly less likely to have surgical (adjusted hazard ratio, 0.40 [95% CI, 0.17-0.96]) or repeat PVI revascularization (adjusted hazard ratio, 0.42 [95% CI, 0.30-0.59]) at 1 year compared with White patients. There was no difference in mortality (adjusted hazard ratio [0.8-1.4]) or major amputation (adjusted hazard ratio, 2.5 [95% CI, 0.8-7.6]) between Black and White patients. CONCLUSIONS: Black patients presenting for PVI were younger, had higher prevalence of comorbidities and lower socioeconomic status. After adjustment, Black patients were less likely to have surgical or repeat PVI revascularization after the index PVI procedure.

Racial, Ethnic, and Socioeconomic Inequities in Access to Left Atrial Appendage Occlusion.

Background Inequitable access to high-technology therapeutics may perpetuate inequities in care. We examined the characteristics of US hospitals that did and did not establish left atrial appendage occlusion (LAAO) programs, the patient populations those hospitals served, and the associations between zip code-level racial, ethnic, and socioeconomic composition and rates of LAAO among Medicare beneficiaries living within large metropolitan areas with LAAO programs. Methods and Results We conducted cross-sectional analyses of Medicare fee-for-service claims for beneficiaries aged 66 years or older between 2016 and 2019. We identified hospitals establishing LAAO programs during the study period. We used generalized linear mixed models to measure the association between zip code-level racial, ethnic, and socioeconomic composition and age-adjusted rates of LAAO in the most populous 25 metropolitan areas with LAAO sites. During the study period, 507 candidate hospitals started LAAO programs, and 745 candidate hospitals did not. Most new LAAO programs opened in metropolitan areas (97.4%). Compared with non-LAAO centers, LAAO centers treated patients with higher median household incomes (difference of $913 [95% CI, $197-$1629], P=0.01). Zip code-level rates of LAAO procedures per 100 000 Medicare beneficiaries in large metropolitan areas were 0.34% (95% CI, 0.33%-0.35%) lower for each $1000 zip code-level decrease in median household income. After adjustment for socioeconomic markers, age, and clinical comorbidities, LAAO rates were lower in zip codes with higher proportions of Black or Hispanic patients. Conclusions Growth in LAAO programs in the United States had been concentrated in metropolitan areas. LAAO centers treated wealthier patient populations in hospitals without LAAO programs. Within major metropolitan areas with LAAO programs, zip codes with higher proportions of Black and Hispanic patients and more patients experiencing socioeconomic disadvantage had lower age-adjusted rates of LAAO. Thus, geographic proximity alone may not ensure equitable access to LAAO. Unequal access to LAAO may reflect disparities in referral patterns, rates of diagnosis, and preferences for using novel therapies experienced by racial and ethnic minority groups and patients experiencing socioeconomic disadvantage.

Surgical Management and Mechanical Circulatory Support in High-Risk Pulmonary Embolisms: Historical Context, Current Status, and Future Directions: A Scientific Statement From the American Heart Association.

Acute pulmonary embolism is the third leading cause of cardiovascular death, with most pulmonary embolism-related mortality associated with acute right ventricular failure. Although there has recently been increased clinical attention to acute pulmonary embolism with the adoption of multidisciplinary pulmonary embolism response teams, mortality of patients with pulmonary embolism who present with hemodynamic compromise remains high when current guideline-directed therapy is followed. Because historical data and practice patterns affect current consensus treatment recommendations, surgical embolectomy has largely been relegated to patients who have contraindications to other treatments or when other treatment modalities fail. Despite a selection bias toward patients with greater illness, a growing body of literature describes the safety and efficacy of the surgical management of acute pulmonary embolism, especially in the hemodynamically compromised population. The purpose of this document is to describe modern techniques, strategies, and outcomes of surgical embolectomy and venoarterial extracorporeal membrane oxygenation and to suggest strategies to better understand the role of surgery in the management of pulmonary embolisms.

Characteristics of Clinical Trial Sites for Novel Transcatheter Mitral and Tricuspid Valvular Therapies.

Importance: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials. Objective: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies. Design, Setting, and Participants: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022. Exposures: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals. Main Outcome and Measures: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies. Results: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials. Conclusions and Relevance: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

Identifying Racial, Ethnic, and Socioeconomic Inequities in the Use of Novel P2Y12 Inhibitors After Percutaneous Coronary Intervention.

BACKGROUND: Novel P2Y12 inhibitors prasugrel and ticagrelor were approved for patients with acute coronary syndrome (ACS) in 2009 and 2011, respectively. We assessed the association of racial, ethnic, and socioeconomic factors with initiation of and adherence to novel P2Y12 inhibitors in a commercially insured population. METHODS: We performed a retrospective cohort analysis of adults undergoing percutaneous coronary intervention with placement of a drug-eluting stent, stratified by ACS status, between January 2008 and December 2016 using Clinformatics Data Mart (OptumInsight). We estimated multivariable logistic regression models to identify factors associated with the initiation of clopidogrel vs novel P2Y12 inhibitors as well as subsequent 6-month medication adherence, assessed via pharmacy records. RESULTS: A total of 55,664 patients were included in the analysis. Hispanic ethnicity was independently associated with the initiation of clopidogrel compared with novel P2Y12 inhibitors among ACS patients (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04-1.36; P<.01). ACS patients with an annual median household income of over $100,000 were less likely to be started on clopidogrel when compared with those who earned less than $40,000 (OR, 0.67; 95% CI, 0.61-0.75; P<.01). Black race, Hispanic ethnicity, and lower household income were each associated with significantly reduced odds of P2Y12 inhibitor adherence. CONCLUSION: Hispanic ethnicity and lower household income were associated with novel P2Y12 inhibitor initiation, and non-White race and ethnicity were associated with lower P2Y12 inhibitor adherence over 6-month follow-up. These findings highlight continued inequity of care, even in an insured population, and point to a need for new strategies to close these gaps.

Current interventional therapies in acute pulmonary embolism.

Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality. The management of PE is currently evolving given the development of new technologies and team-based approaches. This document will focus on risk stratification of PEs, review of the current interventional therapies, the role of clinical endpoints to assess the effectiveness of different interventional therapies, and the role for mechanical circulatory support in the complex management of this disease.

Plasma biomarkers associated with adverse outcomes in patients with calcific aortic stenosis.

AIMS: Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS. METHODS AND RESULTS: We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure-related hospital admission (DHFA). We also utilized machine-learning methods (a tree-based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow-up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)-α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)-23 (HR 1.22, P < 0.0001), N-terminal pro B-type natriuretic peptide (NT-proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase-7 (HR 1.24, P = 0.0002), syndecan-1 (HR 1.27, P = 0.0002), suppression of tumorigenicity-2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)-8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)-3 (HR 1.17, P = 0.001), neutrophil gelatinase-associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF-23 (HR 1.36, P < 0.0001), TNF-α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin-2 (HR 1.26, P < 0.0001), syndecan-1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL-8 (HR 1.18, P = 0.0009), PTX-3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT-proBNP (HR 1.63, P < 0.0001). Machine-learning multimarker models were strongly associated with adverse outcomes (mean 1-year probability of death of 0%, 2%, and 60%; mean 1-year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL-6 (a biomarker of inflammation) and FGF-23 (a biomarker of calcification) emerged as the biomarkers of highest importance. CONCLUSIONS: Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis.

Snare-Assisted Valve Positioning of Self-Expanding Valves for Transcatheter Aortic Valve Replacement.

We describe 4 cases in which technical challenges were anticipated in delivering a self-expanding TAVR valve due to challenging aortic anatomy or a previous placed surgical aortic valve. An upfront snare strategy is described which facilitates valve centralization and atraumatic valve delivery. (Level of Difficulty: Advanced.).

Initial Findings From the North American COVID-19 Myocardial Infarction Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). OBJECTIVES: The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. METHODS: A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. RESULTS: As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients). CONCLUSIONS: COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

Evolution and Outcomes of Premature Coronary Artery Disease.

PURPOSE OF REVIEW: The purpose of this review is to explore the evolution and outcomes of premature coronary artery disease (PCAD) while reviewing strategies for effective screening of those at high risk for developing this disease. RECENT FINDINGS: Premature coronary artery disease (PCAD) affects a population of patients not typically identified as high risk by current risk stratification guidelines or traditional risk calculation tools. Not only does PCAD represent a large proportion of overall cardiovascular disease, it also afflicts a population in which the rate of mortality from cardiovascular disease has plateaued despite an overall declining population-wide cardiovascular mortality rate. There is ample opportunity for behavioral change strategies, screening tools, adapted imaging modalities, and precision pharmacotherapies to be more precisely targeted toward those at highest risk for premature coronary artery disease. Premature coronary artery disease (PCAD) is pervasive and not frequently represented within contemporary risk calculation models. Providers should pursue proactive screening and aggressive risk factor modification and deploy appropriate preventative therapies in caring for younger populations.

Management of Acute Pulmonary Embolism.

PURPOSE OF THE REVIEW: Over 100,000 cardiovascular-related deaths annually are caused by acute pulmonary embolism (PE). While anticoagulation has historically been the foundation for treatment of PE, this review highlights the recent rapid expansion in the interventional strategies for this condition. RECENT FINDINGS: At the time of diagnosis, appropriate risk stratification helps to accurately identify patients who may be candidates for advanced therapeutic interventions. While systemic thrombolytics (ST) is the mostly commonly utilized intervention for high-risk PE, the risk profile of ST for intermediate-risk PE limits its use. Assessment of an individualized patient risk profile, often via a multidisciplinary pulmonary response team (PERT) model, there are various interventional strategies to consider for PE management. Novel therapeutic options include catheter-directed thrombolysis, catheter-based embolectomy, or mechanical circulatory support for certain high-risk PE patients. Current data has established safety and efficacy for catheter-based treatment of PE based on surrogate outcome measures. However, there is limited long-term data or prospective comparisons between treatment modalities and ST. While PE diagnosis has improved with modern cross-sectional imaging, there is interest in improved diagnostic models for PE that incorporate artificial intelligence and machine learning techniques. SUMMARY: In patients with acute pulmonary embolism, after appropriate risk stratification, some intermediate and high-risk patients should be considered for interventional-based treatment for PE.

Outcomes of catheter-directed versus systemic thrombolysis for the treatment of pulmonary embolism: A real-world analysis of national administrative claims.

Catheter-directed thrombolysis (CDT) and systemic thrombolysis (ST) are used to treat intermediate/high-risk pulmonary embolism (PE) in the absence of comparative safety and effectiveness data. We utilized a large administrative database to perform a comparative safety and effectiveness analysis of catheter-directed versus systemic thrombolysis. From the Optum® Clinformatics® Data Mart private-payer insurance claims database, we identified 100,744 patients hospitalized with PE between 2004 and 2014. We extracted demographic characteristics, high-risk PE features, components of the Elixhauser Comorbidity Index, and outcomes including intracranial hemorrhage (ICH), all-cause bleeding, and mortality among all patients receiving CDT and ST. We used propensity score methods to compare outcomes between matched cohorts adjusted for observed confounders. A total of 1915 patients (1.9%) received either CDT (n = 632) or ST (n = 1283). Patients in the CDT group had fewer high-risk features including less shock (5.4 vs 11.1%; p < 0.001) and cardiac arrest (6.8 vs 11.0%; p = 0.004). In 1:1 propensity-matched groups, ICH rates were 1.9% in both the CDT and ST groups (p = 1.0). All-cause bleeding was higher in the CDT group (15.9 vs 8.7%; p < 0.001), while in-hospital mortality was lower (6.5 vs 10.0%; p = 0.02). Among a nationally representative cohort of patients with PE at higher risk for mortality, CDT was associated with similar ICH rates, increased all-cause bleeding, and lower short and intermediate-term mortality when compared with ST. The competing risks and benefits of CDT in real-world practice suggest the need for large-scale randomized clinical trials with appropriate comparator arms.

Interventional Therapies in Acute Pulmonary Embolism.

Treatment of acute pulmonary embolism (PE) historically included anticoagulation and systemic thrombolytic therapy. More recently, catheter guided interventions provided promise of mitigating bleeding risks usually associated with systemic thrombolysis in intermediate to high risk PE patients. Catheter based interventions can broadly be divided into catheter directed thrombolysis and catheter based embolectomy. Both modalities are currently undergoing active research and each has their respective risks and benefits. The decision to administer these advanced therapies for acute PE can be challenging but can be accomplished via a multi-disciplinary PE response team.

Prospective CYP2C19 Genotyping to Guide Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Pragmatic Randomized Clinical Trial.

BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after percutaneous coronary intervention, but the clinical impact of implementing CYP2C19 genotyping in a real-world setting is unknown. The purpose of the study was to determine whether returning CYP2C19 genotype results along with genotype-guided pharmacotherapy recommendations using a rapid turnaround test would change antiplatelet prescribing following percutaneous coronary intervention.The primary outcome was the rate of prasugrel or ticagrelor prescribing in each arm. Secondary outcomes included agreement to the genotype-guided recommendations. METHODS: At the time of percutaneous coronary intervention, participants were randomly assigned to prospective rapid point-of-care genotyping of CYP2C19 major alleles (*2, *3, *17) via salivary swab (genotyped group) or no genotyping (usual care) to guide antiplatelet drug selection. Interventional cardiologists at 2 cardiac catheterization laboratories within the same health system were provided genotype information along with genotype-guided pharmacotherapy recommendations. RESULTS: A total of 504 participants were randomized, 249 to the genotyped and 255 to the usual care group. The participants were primarily men (73%); age, 63±10 years; and 50% had acute coronary syndromes. In the genotyped group, 28% were carriers of loss-of-function alleles (*2, *3). The use of prasugrel or ticagrelor was significantly higher in the genotyped group compared with the usual care group (30% versus 21%; odds ratio, 1.60 [95% CI, 1.07-2.42]; P=0.03). Within the genotyped group, 53% of loss-of-function allele carriers were started on prasugrel/ticagrelor, while 47% were started on clopidogrel. CONCLUSIONS: In a randomized controlled trial of clinical CYP2C19 genotyping implementation, pharmacogenetic test results significantly influenced antiplatelet drug prescribing; however, almost half of CYP2C19 loss-of-function carriers continued to receive clopidogrel. Interventional cardiologists consider both clinical and genetic factors when selecting antiplatelet therapy following percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02508116.