Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study.

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.

ACR Appropriateness Criteria® Vascular Claudication-Assessment for Revascularization.

Vascular claudication is a symptom complex characterized by reproducible pain and weakness in an active muscle group due to peripheral arterial disease. Noninvasive hemodynamic tests such as the ankle brachial index, toe brachial index, segmental pressures, and pulse volume recordings are considered the first imaging modalities necessary to reliably establish the presence and severity of arterial obstructions. Vascular imaging is consequently used for diagnosing individual lesions and triaging patients for medical, percutaneous, or surgical intervention. Catheter angiography remains the reference standard for imaging the peripheral arteries, providing a dynamic and accurate depiction of the peripheral arteries. It is particularly useful when endovascular intervention is anticipated. When combined with noninvasive hemodynamic tests, however, noninvasive imaging, including ultrasound, CT angiography, and MR angiography, can also reliably confirm or exclude the presence of peripheral arterial disease. All modalities, however, have their own technical limitations when classifying the location, extent, and severity of disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Normal ventricular diameter ratio on CT provides adequate assessment for critical right ventricular strain among patients with acute pulmonary embolism.

There is variability in guideline recommendations for assessment of the right ventricle (RV) with imaging as prognostic information after acute pulmonary embolism (PE). The objective of this study is to identify a clinical scenario for which normal CT-derived right-to-left ventricular (RV/LV) ratio is sufficient to exclude RV strain or PE-related short-term death. This retrospective cohort study included 579 consecutive subjects (08/2003-03/2010) diagnosed with acute PE with normal CT-RV/LV ratio (<0.9), 236 of whom received subsequent echocardiography. To identify a clinical scenario for which CT-RV/LV ratio was considered sufficient to exclude RV strain or PE-related short-term death, a multivariable logistic model was created to detect factors related to subjects for whom subsequent echocardiography detected RV strain or those who did not receive echocardiography and died of PE within 14 days (n = 55). The final model included five variables (c-statistic = 0.758, over-fitting bias = 2.52 %): congestive heart failure (adjusted odds ratio, OR 4.32, 95 % confidence interval, CI 1.88-9.92), RV diameter on CT >45 mm (OR 3.07, 95 % CI 1.56-6.03), age >60 years (OR 2.59, 95 % CI 1.41-4.77), central embolus (OR 1.96, 95 % CI 1.01-3.79), and stage-IV cancer (OR 1.94, 95 % CI 0.99-3.78). If these five factors were all absent (37.1 % of the population), the probability that "CT-RV/LV ratio is sufficient to exclude RV strain/PE-related short-term death" was 0.97 (95 % CI = 0.95-0.99). Normal CT-RV/LV ratio plus readily obtained five clinical predictors were adequate to exclude RV strain or PE-related short-term mortality.

Comparative Effectiveness of Carotid Artery Stenting Versus Carotid Endarterectomy Among Medicare Beneficiaries.

BACKGROUND: Effectiveness of carotid artery stenting (CAS) relative to carotid endarterectomy (CEA) among Medicare patients has not been established. We compared effectiveness of CAS versus CEA among Medicare beneficiaries. METHODS AND RESULTS: We linked Medicare data (2000-2009) to the Society for Vascular Surgery's Vascular Registry (2005-2008) and the National Cardiovascular Data Registry's (NCDR) Carotid Artery Revascularization and Endarterectomy Registry (2006-2008/2009). Medicare patients were followed up from procedure date until death, stroke/transient ischemic attack, periprocedural myocardial infarction, or a composite end point for these outcomes. We derived high-dimensional propensity scores using registry and Medicare data to control for patient factors and adjusted for provider factors in a Cox regression model comparing CAS with CEA. Among 5254 Society for Vascular Surgery's Vascular Registry (1999 CAS; 3255 CEA) and 4055 Carotid Artery Revascularization and Endarterectomy Registry (2824 CAS; 1231 CEA) Medicare patients, CAS patients had a higher comorbidity burden and were more likely to be at high surgical risk (Society for Vascular Surgery's Vascular Registry: 96.7% versus 44.5%; Carotid Artery Revascularization and Endarterectomy Registry: 71.3% versus 44.7%). Unadjusted outcome risks were higher for CAS. Mortality risks remained elevated for CAS after adjusting for patient-level factors (hazard ratio, 1.24; 95% confidence interval, 1.06-1.46). After further adjustment for provider factors, differences between CAS and CEA were attenuated or no longer present (hazard ratio for mortality, 1.13; 95% confidence interval, 0.94-1.37). Performance was comparable across subgroups defined by sex and degree of carotid stenosis, but there was a nonsignificant trend suggesting a higher risk of adverse outcomes in older (>80) and symptomatic patients undergoing CAS. CONCLUSIONS: Outcomes after CAS and CEA among Medicare beneficiaries were comparable after adjusting for both patient- and provider-level factors.

Relationship Between Physician and Hospital Procedure Volume and Mortality After Carotid Artery Stenting Among Medicare Beneficiaries.

BACKGROUND: Clinical trials demonstrated the efficacy of carotid artery stenting (CAS) relative to carotid endarterectomy when performed by physicians with demonstrated proficiency. It is unclear how CAS performance may be influenced by the diversity in CAS and non-CAS provider volumes in routine clinical practice. METHODS AND RESULTS: We linked Medicare claims to the Centers for Medicare and Medicaid Services' CAS Database (2005-2009). We assessed the association between 30-day mortality and past-year physician (0, 1-4, 5-9, 10-19, ≥20) and hospital (<10, 10-19, 20-39, ≥40) CAS volumes and past-year hospital coronary and peripheral stenting volumes (<200, 200-399, 400-849, ≥850) among beneficiaries at least 66 years of age. Unadjusted 30-day mortality risk was 1.8% (95% confidence interval [CI], 1.6-2.0) for 19 724 patients undergoing CAS by 2045 physicians in 729 hospitals. Median past-year CAS volume was 9 (interquartile range, 4-19) for physicians and 23 (interquartile range, 12-41) for hospitals. Compared to physicians performing ≥20 CAS in the past year, lower CAS volumes were associated with higher adjusted risks of 30-day morality (P value for trend < 0.05): 1.4 (95% CI, 0.9-2.3) for 0 past-year CAS, 1.3 (95% CI, 0.9-1.8) for 1 to 4, 1.1 (95% CI, 0.8-1.6) for 5 to 9, and 0.9 (95% CI, 0.7-1.4) for 10 to 19. An inverse relationship between 30-day mortality and past-year CAS hospital volume as well as past-year hospital non-CAS volume, past-year hospital non-CAS volume, and 30-day mortality was also noted. CONCLUSIONS: Among Medicare patients, an inverse relationship exists between physician and hospital CAS volumes and hospital non-CAS stenting volume and 30-day mortality, even after adjusting for all pertinent patient- and hospital-level factors.

Surgeon case volume and 30-day mortality after carotid endarterectomy among contemporary medicare beneficiaries: before and after national coverage determination for carotid artery stenting.

BACKGROUND AND PURPOSE: After the 2005 National Coverage Determination to reimburse carotid artery stenting (CAS) for Medicare beneficiaries, the number of CAS procedures increased and carotid endarterectomy (CEA) decreased. We evaluated trends in surgeons' past-year CEA case-volume and 30-day mortality after CEA, and their association before and after the National Coverage Determination. METHODS: In a retrospective cohort study of patients undergoing CEA (2001-2008) and CAS (2005-2008) using Medicare data, we described yearly trends of CEA and CAS rates, patient characteristics, and 30-day mortality after CEA. We used logistic regression adjusting for patient- and surgeon-level factors to assess the effect of surgeon case volume on 30-day mortality after CEA. RESULTS: We identified 454 717 CEA and 27 943 CAS patients. Patients undergoing CEA in recent years were older and had more comorbidities than earlier years. CEA rates per 10 000 beneficiaries declined from 18.1 in 2002 to 12.7 in 2008, whereas median surgeon past-year case-volume declined from 27 to 21. The CAS rates peaked at 2.3 per 10 000 beneficiaries in 2006 but declined to 1.8 in 2008, resulting in declining overall revascularization procedure rates during 2005 to 2008. Thirty day post-CEA mortality was 1.40% (95% confidence interval, 1.34-1.47) in 2001 to 2002 and 1.17% (1.10-1.24) in 2007 to 2008. Surgeon's past-year case-volume of <10 was associated with higher 30-day mortality consistently during 2001 to 2008. CONCLUSIONS: The rate of CEA procedures decreased substantially during 2001 to 2008, as did surgeon past-year case-volume. The postprocedural mortality in Medicare beneficiaries was high compared with trial patients but somewhat improved over time. Those operated by lower past-year case-volume surgeons had increased mortality.

Outcomes after carotid artery stenting in Medicare beneficiaries, 2005 to 2009.

IMPORTANCE: Despite increased carotid artery stenting (CAS) dissemination following the 2005 National Coverage Determination, to our knowledge, periprocedural and long-term outcomes have not been described among Medicare beneficiaries. OBJECTIVE: To describe the incidence of outcomes during and after the periprocedural period among Medicare beneficiaries undergoing CAS. DESIGN, SETTING, AND PARTICIPANTS: Observational study with a mean follow-up time of approximately 2 years among 22,516 fee-for-service Medicare beneficiaries at least 66 years old undergoing CAS (2005-2009) who were linked to the Centers for Medicare & Medicaid Services' CAS database. Database procedure dates were required to fall during a Medicare hospitalization for CAS. MAIN OUTCOMES AND MEASURES: Periprocedural (30-day) and long-term risks of mortality and stroke or transient ischemic attack, as well as periprocedural myocardial infarction. Subgroups were based on sociodemographic, clinical, and center-level factors, as well as the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial or Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) enrollment criteria. RESULTS: The mean patient age was 76.3 years, 60.5% were male, 93.8% were of white race, 91.2% were at high surgical risk, 47.4% were symptomatic, and 97.4% had carotid stenosis of at least 70%. Crude 30-day mortality, stroke or transient ischemic attack, and myocardial infarction risks were 1.7% (95% CI, 1.5%-1.8%), 3.3% (95% CI, 3.0%-3.5%), and 2.5% (95% CI, 2.3%-2.7%), respectively. Mortality during a mean follow-up time of 2 years was 32.0% (95% CI, 31.0%-33.0%), with rates of 37.3% (95% CI, 35.8%-38.7%) among symptomatic patients and 27.7% (95% CI, 26.4%-28.9%) among asymptomatic patients. Older age, symptomatic carotid stenosis, and nonelective hospital admission were associated with increased adjusted hazards of mortality and stroke or transient ischemic attack during and after the periprocedural period. The presence of a stroke center, government ownership, and a hospital bed capacity of 500 or more were associated with increased adjusted hazards of periprocedural mortality and stroke or transient ischemic attack. Few patients met the SAPPHIRE trial or CREST enrollment criteria primarily because physicians did not meet proficiency requirements either due to exceeding periprocedural complication trial thresholds or not meeting minimum CAS volume requirements. CONCLUSIONS AND RELEVANCE: Competing risks may limit the benefits of CAS in certain Medicare beneficiaries, particularly among older and symptomatic patients who have higher periprocedural and long-term mortality risks. The generalizability of trials like the SAPPHIRE or CREST to the Medicare population may be limited, underscoring the need to evaluate real-world effectiveness of carotid stenosis treatments.

Choosing wisely for syncope: low-value carotid ultrasound use.

BACKGROUND: The United States spends more than $750 billion annually on tests and procedures that do not benefit patients. Although there is no physiological indication for carotid ultrasound in "simple" syncope in the absence of focal neurological signs or symptoms suggestive of stroke, there is concern that this practice remains common for routine syncope workups. METHODS AND RESULTS: We used a 5% random-sample Medicare claims database to evaluate large-scale national trends in utilization of low-value carotid ultrasound imaging for simple syncope. We found that 16.5% of all Medicare beneficiaries with simple syncope underwent carotid imaging and 6.5% of all carotid ultrasounds ordered in 2009 were for this low-value indication. These findings were complemented by a manual chart review of 313 patients at a large academic medical center who underwent carotid ultrasound for simple syncope over a 5-year period. For the 48 (15.4%) of 313 patients with stenosis ≥50%, carotid ultrasound did not yield a causal diagnosis. Only 2% of the 313 patients imaged experienced a change in medications after a positive study, and <1% of patients underwent a carotid revascularization procedure. CONCLUSIONS: These data suggest that carotid ultrasound for patients with uncomplicated syncope are still commonly ordered and may be an easy target for institutions striving to curtail low-value care.

Guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology.

Accompanying the rapid growth of interest in percutaneous vascular interventions, there has been increasing interest among cardiologists in performing noninvasive vascular testing using ultrasound. In an attempt to provide recommendations on the best practices in vascular laboratory testing, this report has been prepared by a writing group from the American Society of Echocardiography (ASE) and the Society for Vascular Medicine and Biology. The document summarizes principles integral to vascular duplex ultrasound--including color Doppler, spectral Doppler waveform analysis, power Doppler, and the use of contrast. Appropriate indications and interpretation of carotid artery, renal artery, abdominal aorta, and peripheral artery ultrasound imaging are described. A dedicated section summarizes noninvasive techniques for physiologic vascular testing of the lower extremity arteries--including measurement of segmental pressures and pulse volume plethysmography. The use of exercise testing in the evaluation of peripheral artery disease, ultrasound evaluation of the lower extremities after percutaneous revascularization, and the diagnosis and management of iatrogenic pseudoaneurysm (PSA) is also discussed. A section on the important topic of vascular laboratory accreditation is included. Finally, additional details regarding proper technique for performance of the various vascular tests and procedures are included in the Appendix.

Abnormal cytology predicts poor prognosis in cancer patients with pericardial effusion.

PURPOSE: Pericardial tamponade is a life-threatening disorder caused by varying medical conditions. Malignancy and complications of its treatment are a common cause of pericardial effusion. The natural history of pericardial effusion remains largely unknown. We investigated the association of malignancy with adverse outcomes after pericardiocentesis. PATIENTS AND METHODS: Consecutive patients undergoing pericardiocentesis at a single institution between January 1, 1999, and January 31, 2003, were included. Death was confirmed with the Social Security Death Index. Survival estimates were obtained by the Kaplan-Meier method. Cox regression was performed to determine the clinical characteristics associated with death. RESULTS: Two hundred nineteen patients underwent pericardiocentesis during the study period. The effusion was cancer-related in 43.8% of cases. Median survival was 59.6 weeks (95% CI, 24.3 to 94.8 weeks). During the follow-up period, 47.9% of patients died. Cancer-related pericardial effusion was associated with decreased survival (median, 15.1 weeks). Abnormal fluid cytology was further associated with poor prognosis among patients with malignancy (median survival, 7.3 v 29.7 weeks; P = .022). Patients with cancer-related pericardial effusion were more likely to require repeat pericardiocentesis (OR = 6.0; P = .001) and pericardial surgery (odds ratio [OR] OR = 5.7; P < .001). Cancer-related effusion and abnormal cytology were independent predictors of death in a multivariate model. CONCLUSION: Malignancy is the most common cause of pericardial effusion in a tertiary care center. Cancer-related pericardial effusion is associated with adverse outcomes, and abnormal cytology further worsens prognosis. The poor survival among cancer patients with pericardial effusion and abnormal fluid cytology may have important implications for management.

Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.

Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology.