Characterization of peripheral artery disease and associations with traditional risk factors, mobility, and biomarkers in the project baseline health study.

BACKGROUND: There is a dearth of research on immunophenotyping in peripheral artery disease (PAD). This study aimed to describe the baseline characteristics, immunophenotypic profile, and quality of life (QoL) of participants with PAD in the Project Baseline Health Study (PBHS). METHODS: The PBHS study is a prospective, multicenter, longitudinal cohort study that collected clinical, molecular, and biometric data from participants recruited between 2017 and 2018. In this analysis, baseline demographic, clinical, mobility, QoL, and flow cytometry data were stratified by the presence of PAD (ankle brachial index [ABI] ≤0.90). RESULTS: Of 2,209 participants, 58 (2.6%) had lower-extremity PAD, and only 2 (3.4%) had pre-existing PAD diagnosed prior to enrollment. Comorbid smoking (29.3% vs 14%, P < .001), hypertension (54% vs 30%, P < .001), diabetes (25% vs 14%, P = .031), and at least moderate coronary calcifications (Agatston score >100: 32% vs 17%, P = .01) were significantly higher in participants with PAD than in those with normal ABIs, as were high-sensitivity C-reactive protein levels (5.86 vs 2.83, P < .001). After adjusting for demographic and risk factors, participants with PAD had significantly fewer circulating CD56-high natural killer cells, IgM+ memory B cells, and CD10/CD27 double-positive B cells (P < .05 for all). CONCLUSIONS: This study reinforces existing evidence that a large proportion of PAD without claudication may be underdiagnosed, particularly in female and Black or African American participants. We describe a novel immunophenotypic profile of participants with PAD that could represent a potential future screening or diagnostic tool to facilitate earlier diagnosis of PAD. GOV IDENTIFIER: NCT03154346, https://clinicaltrials.gov/ct2/show/NCT03154346.

Impact of risk factor control on peripheral artery disease outcomes and health disparities.

BACKGROUND: Peripheral artery disease (PAD) is associated with modifiable atherosclerotic risk factors like hypertension, diabetes, hyperlipidemia, and smoking. However, the effect of risk factor control on outcomes and disparities in achieving control is less well understood. METHODS: All patients in an integrated, regional health system with PAD-related encounters, fee-for-service Medicare, and clinical risk factor control data were identified. Component risk factors were dichotomized into controlled and uncontrolled categories (control defined as low-density lipoprotein < 100 mg/dL, hemoglobin A1c < 7.0%, SBP < 140 mmHg, and current nonsmoker) and composite categories (none, 1, ⩾ 2 uncontrolled RFs) created. The primary outcome was major adverse vascular events (MAVE, a composite of all-cause mortality, myocardial infarction, stroke, and lower-extremity revascularization and amputation). RESULTS: The cohort included 781 patients with PAD, average age 72.5 ± 9.8 years, of whom 30.1% were Black, and 19.1% were Medicaid dual-enrolled. In this cohort, 260 (33.3%) had no uncontrolled risk factors and 200 (25.6%) had two or more uncontrolled risk factors. Patients with the poorest risk factor control were more likely to be Black (p < 0.001), Medicaid dual-enrolled (p < 0.001), and have chronic limb-threatening ischemia (p = 0.009). Significant differences in MAVE by degree of risk factor control were observed at 30 days (none uncontrolled: 5.8%, 1 uncontrolled: 11.5%, ⩾ 2 uncontrolled: 13.6%; p = 0.01) but not at 1 year (p = 0.08). risk factor control was not associated with outcomes at 1 year after adjustment for patient and PAD-specific characteristics. CONCLUSIONS: risk factor control is poor among patients with PAD. Significant disparities in achieving optimal risk factor control represent a potential target for reducing inequities in outcomes.

Contemporary Medical Therapies for Patients with Peripheral Artery Disease and Concomitant Type 2 Diabetes Mellitus: a Review of Current Evidence.

PURPOSE OF REVIEW: The purpose of this review is to highlight the evidence behind landmark trials involving these two novel drug classes in conjunction with a review of long-standing therapies used to improve cardiovascular (CV) outcomes among patients with peripheral artery disease (PAD) patients and type 2 diabetes mellitus (T2DM). RECENT FINDINGS: Recently, societal guideline recommendations have expanded the management of T2DM to incorporate therapies with CV risk factor modification. This is due to CV outcome trials (CVOT) uncovering advantageous cardioprotective effects of several novel therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Providers who manage high-risk patients with T2DM, such as those with concomitant PAD, are expected to incorporate these novel medical therapies into routine patient care. The body of evidence surrounding GLP-1 RA demonstrates a strong benefit in mitigating the innate heightened CV risk among patients with T2DM. Furthermore, SGLT2i not only have a favorable CV profile but also reduce the risk of HF hospitalizations and progression of renal disease. Patients with T2DM and PAD are known to be at a heightened risk for major adverse cardiac and lower extremity events, heart failure, and chronic kidney disease. As such, the use of novel therapies such as GLP-RA and SGLT2i should be strongly considered to minimize morbidity and mortality in this vulnerable population.

The association of healthcare disparities and patient-specific factors on clinical outcomes in peripheral artery disease.

BACKGROUND: PAD increases the risk of cardiovascular mortality and limb loss, and disparities in treatment and outcomes have been described. However, the association of patient-specific characteristics with variation in outcomes is less well known. METHODS: Patients with PAD from Duke University Health System (DUHS) between January 1, 2015 and March 31, 2016 were identified. PAD status was confirmed through ground truth adjudication and predictive modeling using diagnosis codes, procedure codes, and other administrative data. Symptom severity, lower extremity imaging, and ankle-brachial index (ABI) were manually abstracted from the electronic health record (EHR). Data was linked to Centers for Medicare and Medicaid Services data to provide longitudinal follow up. Primary outcome was major adverse vascular events (MAVE), a composite of all-cause mortality, myocardial infarction (MI), stroke, lower extremity revascularization and amputation. RESULTS: Of 1,768 patients with PAD, 31.6% were asymptomatic, 41.2% had intermittent claudication (IC), and 27.3% had chronic limb-threatening ischemia (CLTI). At 1 year, patients with CLTI had higher rates of MAVE compared with asymptomatic or IC patients. CLTI and Medicaid dual eligibility were independent predictors of mortality. CLTI and Black race were associated with amputation. CONCLUSIONS: Rates of MAVE were highest in patients with CLTI, but patients with IC or asymptomatic disease also had high rates of adverse events. Black and Medicaid dual-eligible patients were disproportionately present in the CLTI subgroup and were at higher risk of amputation and mortality, respectively. Future studies must focus on early identification of high-risk patient groups to improve outcomes in patients with PAD.

Case Volumes and Outcomes Among Early-Career Interventional Cardiologists in the United States.

BACKGROUND: Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non-early-career interventional cardiologists in the United States. OBJECTIVES: This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022. METHODS: Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated. RESULTS: A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non-early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non-early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non-early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non-early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non-early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status. CONCLUSIONS: Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

Patient-Reported Outcome Measures in Symptomatic, Non-Limb-Threatening Peripheral Artery Disease: A State-of-the-Art Review.

Patient-reported outcome measures (PROMs) are health outcomes directly reported by the patient that can be used to measure the effect of disease and treatments on patient perceived well-being. This review summarizes current evidence regarding the validation of PROMs in people with symptomatic, nonlimb-threatening peripheral artery disease. A literature search was conducted to identify studies of symptomatic peripheral artery disease without limb-threatening ischemia that included PROMs and had sample sizes ≥25. PROMs were summarized along a continuum of validation using classical test theory framework and according to whether they fulfilled defined criteria for (1) content validity; (2) psychometric validation; and (3) further validation evidence base expansion. Of 2198 articles identified, 157 (7.1%) met inclusion criteria. Twenty-four PROMs in patients with symptomatic peripheral artery disease were reviewed. Among disease-specific PROMs, 8 of 15 had excellent reliability as measured by a Cronbach alpha ≥0.80. Based on established criteria for PROM responsiveness, 6 of 15 disease-specific PROMs demonstrated excellent sensitivity to change. Of these, the disease-specific peripheral artery questionnaire, vascular quality of life questionnaire, and walking impairment questionnaire met criteria for validation at each stage of the continuum. For generic (nondisease specific) PROMs, the European Quality of Life 5-Dimension and SF-36 had the most extensive evidence of validation. Evidence from this review can inform selection of PROMs aligned with scientific and clinical goals, given the variable degree of validation and potential complementary nature of the measures.

Clinician Specialty, Access to Care, and Outcomes Among Patients with Peripheral Artery Disease.

BACKGROUND: Understanding the relationship between patterns of peripheral artery disease and outcomes is an essential step toward improving care and outcomes. We hypothesized that clinician specialty would be associated with occurrence of major adverse vascular events (MAVE). METHODS: Patients with at least 1 peripheral artery disease-related encounter in our health system and fee-for-service Medicare were divided into groups based on the specialty of the clinician (ie, cardiologist, surgeon, podiatrist, primary care, or other) providing a plurality of peripheral artery disease-coded care in the year prior to index encounter. The primary outcome was MAVE (a composite of all-cause mortality, myocardial infarction, stroke, lower extremity revascularization, and lower extremity amputation). RESULTS: The cohort included 1768 patients, of whom 30.0% were Black, 23.9% were Medicaid dual-enrollment eligible, and 31.1% lived in rural areas. Patients receiving a plurality of their care from podiatrists had the highest 1-year rates of MAVE (34.4%, P <.001), hospitalization (65.9%, P <.001), and amputations (22.6%, P <.001). Clinician specialty was not associated with outcomes after adjustment. Patients who were Medicaid dual-eligible had higher adjusted risks of mortality (adjusted hazard ratio [HRadj] 1.54, 95% confidence interval [CI] 1.11-2.14) and all-cause hospitalization (HRadj 1.20, 95% CI 1.03-1.40) and patients who were Black had a higher adjusted risk of amputation (HRadj 1.49, 95% CI 1.03-2.15). CONCLUSIONS: Clinician specialty was not associated with worse outcomes after adjustment, but certain socioeconomic factors were. The effects of clinician specialty and socioeconomic status were likely attenuated by the fact that all patients in this study had health insurance; these analyses require confirmation in a more representative cohort.

Characteristics and Outcomes of Patients With Diabetes Mellitus Undergoing Peripheral Vascular Intervention for Infrainguinal Symptomatic Peripheral Artery Disease.

PURPOSE: Patients with diabetes mellitus (DM) are known to be at higher risk for peripheral artery disease (PAD), amputations, and major adverse cardiovascular events, though it is unclear whether they are at any higher risk for repeat intervention. LIBERTY 360 offered an opportunity to study a real-world cohort of patients who underwent distal superficial femoral artery endovascular revascularizations. We aimed to describe patients with DM, their outcomes following peripheral vascular intervention, and the effect of DM on outcomes in the LIBERTY 360 cohort. METHODS: LIBERTY 360 is a prospective, multi-center, non-randomized, mono-industry funded observational study of patients undergoing endovascular revascularization. Outcomes included 30-day and 1-year all-cause mortality, major amputation, target vessel/lesion revascularization, and a composite of those events. A multivariable regression model including DM was constructed to examine the effect of DM on outcomes. Multivariable survival estimates were made using Cox proportional hazards models. RESULTS: A total of 1,204 patients were enrolled, of whom 727 had DM (60.4%). Patients with DM had significantly more comorbidities and a third required insulin for DM management. Patients with DM had more severe disease based on Rutherford classification at baseline. After adjusting for comorbidities and disease severity, DM patients had more frequent major amputations at 1 year (5.2% versus 1.2%; HR 2.71, 95%CI 1.05-6.98, p = 0.040). The 1-year rates of all-cause mortality and target vessel/lesion revascularization were not significantly higher for patients with DM. CONCLUSIONS: Diabetes mellitus was associated with increased major amputations at 1 year following endovascular revascularization after accounting for demographics, comorbidities, and PAD-related characteristics. Further research is needed to determine which aspects of PAD and DM are most strongly associated with poor outcomes following lower extremity revascularization.

The impact of chronic kidney disease on outcomes following peripheral vascular intervention.

BACKGROUND: Patients with chronic kidney disease (CKD) have worsened clinical outcomes following percutaneous coronary intervention; however, limited evidence exists in patients undergoing peripheral vascular intervention (PVI). PURPOSE: We aimed to assess the effect of CKD on outcomes following PVI for symptomatic peripheral artery disease. METHODS: Using patients from the LIBERTY 360 study, we compared the rates of 30 day and 1 year major adverse vascular events (MAVE), a composite of all-cause mortality, major amputation, and target vessel/lesion revascularization, between patients with and without CKD (estimated glomular filtration rate less than 60) following PVI. Multivariable adjustment was performed to assess for independent association between CKD and outcomes. RESULTS: Among 1189 patients enrolled, 378 patients (31.8%) had CKD. At 1 year, patients with CKD had higher rates of MAVE (34.6% vs 25.6%), all-cause mortality (11.9% vs 5.5%), and major amputation (5.9% vs 2.6%) when compared with patients without CKD (all P < .05). After adjustment, patients with CKD had higher risks of 1-year MAVE (HR 1.30, 95% CI 1.04-1.64; P = .023) and all-cause mortality (HR 1.88, 95% CI 1.22-2.91; P = .005) when compared with patients without CKD. There was no statistically significant difference in risk of major amputations (HR 1.70, 95% CI 0.91-3.17; P = .094). CONCLUSIONS: Despite high procedural success and low amputation rates, patients with CKD remain at greater risk for MAVE and all-cause mortality after PVI. Further research is needed to determine treatment strategies to mitigate substantial mortality risk in this vulnerable population.

Association of Disease Progression With Cardiovascular and Limb Outcomes in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

BACKGROUND: Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association of changes in symptom classification with subsequent cardiovascular disease events. METHODS: In this analysis of the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease), we examined the changes in Rutherford classification (RC) of patients over 12 months. We examined the baseline characteristics of patients by change in symptom classification at 12 months (improved=decreased RC, no change, or worsened=increased RC), and the association between changes in symptom classification (RC) at 12 months and subsequent cardiovascular disease events. RESULTS: Among 12 759 patients, 3240 (25%) were classified as improved by RC at 12 months, 8132 (64%) as no change, and 1387 (11%) as worsened. At 12 months, many patients who were asymptomatic or had mild/moderate claudication at enrollment had no change in symptom classification over 12 months (73.7% and 70.9%). Patients who worsened over 12 months were more likely to have comorbidities (diabetes mellitus and prior myocardial infarction) and more events (myocardial infarction, amputation, and major bleeding) by 12 months postrandomization, all P<0.001. Worsened symptom classification over 12 months was associated with increased risk of all-cause death (adjusted hazard ratio, 1.29 [95% CI, 1.03-1.62]), major amputation (adjusted hazard ratio, 4.12 [95% CI, 2.46-6.88]), and a composite of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio, 1.30 [95% CI, 1.05-1.62]), all P<0.05 after 12 months postrandomization. CONCLUSIONS: Patients with comorbidities and prior history of cardiovascular disease events at baseline and within the first 12 months of the trial were more likely to have worsened symptom classification at 12 months. Worsening symptom classification over 12 months was associated subsequently with an increased risk of all-cause death, amputation, and a composite of cardiovascular death, myocardial infarction, or stroke. Graphic Abstract: A graphic abstract is available for this article.

Wearable Cardioverter Defibrillator "The Lifevest": Device Design, Limitations, and Areas of Improvement.

Sudden cardiac death is a potentially fatal clinical event demanding use of emergent intervention such as defibrillation. Over the last 1 decade, development of devices such as implantable and wearable cardioverter defibrillators (WCD) has provided new avenues in the management of sudden cardiac death. Several clinical studies have commented on the therapeutic and preventive aspect of WCD, however, literature describing the device functioning and limitations is limited. In this review study, we describe the technical aspects and limitations of WCD with a focus on identifying potential areas of improvement and framework for future research studies.

A Rare Case of Transient Proximal Renal Tubular Acidosis in Pregnancy.

Renal tubular acidosis (RTA) is a disorder that has improper function of renal acid-base regulation and is rarely encountered during pregnancy. Currently, there is no clear evidence on management and outcomes in patients with this condition. We report a case of a previously healthy 23-year-old female at 30 weeks of gestation who presented with proximal RTA and had spontaneous resolution of the condition shortly after delivery.

A rare case of emphysematous pyelonephritis in a renal transplant patient.

Emphysematous pyelonephritis (EPN) is a rare life-threatening complication of a properly functioning renal allograft leading to potential graft loss and hemodialysis. Currently, no clear management guidelines exist in these clinically challenging immunosuppressed renal transplant recipients. We report a case of a 62-year-old woman who presented with class 4 EPN and was managed with intravenous antibiotics and nephrectomy at our medical center.