Publications

PURPOSE OF REVIEW: Peripheral artery disease (PAD) is a common, debilitating disease that impacts 8.5 million Americans and carries a poor prognosis. The most common manifestation of lower extremity PAD is claudication-a condition which significantly reduces quality of life and functional status. Paclitaxel-coated balloons and stents (PCBs and PESs) represented a breakthrough in the ability to treat medication-refractory patients relative to bare metal stents (BMSs) and percutaneous transluminal angioplasty (PTA) because they improve primary patency rates, reduce target lesion revascularization (TLR), and minimize late-lumen loss for femoropopliteal lesions. As a result, paclitaxel-coated devices (PCDs) were swiftly established as the standard of care for revascularization of femoropopliteal artery disease. A recent meta-analysis of summary-level data demonstrated a late mortality signal for patients treated with paclitaxel-coated devices relative to uncoated devices. This has had a major impact on the vascular community and for the treatment of patients with PAD. Herein, we provide a detailed review of the available data on the late mortality signal associated with paclitaxel.

RECENT FINDINGS: In December of 2018, Katsanos et al. J Am Heart Assoc 7: e011245, 2018) published data from randomized-controlled trials (RCTs) that demonstrated an increase in mortality at 2 and 5 years in patients treated with PCDs involving the femoropopliteal arterial segment relative to patients treated with uncoated devices. As a result of this analysis, randomized trials were stopped and the FDA sent a letter to healthcare providers recommending restriction of use of these devices to patients at the highest risk of restenosis. As additional data emerged supporting the safety of these devices, the FDA organized an advisory committee meeting to review the available data and to determine a pathway forward. The FDA concluded that there were insufficient data to make a final decision regarding the safety of PCDs. They allowed these devices to remain on the market, but with revised safety labeling and updated their letter to healthcare providers to continue to restrict use to patients at highest risk of reintervention. The FDA also called for additional long-term data, including from RCTs and real-world data. To date, an updated patient-level meta-analysis of clinical trial data, RCTs with longer-term follow-up, and large observational studies have been conducted. While meta-analyses conducted using overlapping clinical trial data have found a persistent increase in mortality for those treated with PCDs, individual industry-sponsored RCTs and large observational studies have consistently failed to detect a corresponding mortality increase. To date, no mechanism linking paclitaxel to mortality has been observed. We are currently at an impasse for drawing definitive conclusions regarding the long-term safety of paclitaxel-coated devices. As we await enrollment in ongoing clinical trials, we must proceed with making reasonable decisions for our patients' care from the available data, as these devices have important clinical implications for our patients. A critical lesson that can be learned from this controversy is that, for future device trials, committing to long-term follow-up is crucial.

Background It is unknown whether clinical events identified with administrative claims have similar prognosis compared with trial-adjudicated events in cardiovascular clinical trials. We compared the prognostic significance of claims-based end points in context of trial-adjudicated end points in the DAPT (Dual Antiplatelet Therapy) study. Methods and Results We matched 1336 patients aged ≥65 years who received percutaneous coronary intervention in the DAPT study with the CathPCI registry linked to Medicare claims. We compared death at 21 months post-randomization using Cox proportional hazards models among patients with ischemic events (myocardial infarction or stroke) and bleeding events identified by: (1) both trial adjudication and claims; (2) trial adjudication only; and (3) claims only. A total of 47 patients (3.5%) had ischemic events identified by both trial adjudication and claims, 24 (1.8%) in trial adjudication only, 15 (1.1%) in claims only, and 1250 (93.6%) had no ischemic events, with annualized unadjusted mortality rates of 12.8, 5.5, 14.9, and 1.26 per 100 person-years, respectively. A total of 44 patients (3.3%) had bleeding events identified with both trial adjudication and claims, 13 (1.0%) in trial adjudication only, 65 (4.9%) in claims only, and 1214 (90.9%) had no bleeding events, with annualized unadjusted mortality rates of 11.0, 16.8, 10.7, and 0.95 per 100 person-years, respectively. Among patients with no trial-adjudicated events, patients with events in claims only had a high subsequent adjusted mortality risk (hazard ratio (HR) ischemic events: 31.5; 95% CI, 8.9‒111.9; HR bleeding events 23.9; 95% CI, 10.7‒53.2). Conclusions In addition to trial-adjudicated events, claims identified additional clinically meaningful ischemic and bleeding events that were prognostically significant for death.

PURPOSE: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD).

MATERIALS AND METHODS: The LIBERTY trial (ClinicalTrials.gov identifier NCT01855412) was a prospective, observational, core laboratory-assessed, multicenter study of endovascular interventions enrolling >1200 participants treated at 51 sites. Data from 1189 patients were stratified according to Rutherford category (RC) and analyzed [RC 2-3 (n=500), RC 4-5 (n=589), and RC 6 (n=100)]. The primary outcomes were major amputation of the target limb and all-cause death; secondary outcomes were target vessel revascularization (TVR) or target lesion revascularization (TLR); major adverse events (MAEs; death within 30 days, TVR or TLR, and major amputation); death or major amputation combined; and change in self-reported quality of life (QoL) measures (VascuQol-25). The Kaplan-Meier (KM) method was employed to estimate the outcomes; estimates are presented with the 95% confidence intervals (CI). Predictors of 3-year MAE, death, TVR, and major amputation were analyzed using Cox proportional hazard regression modeling.

RESULTS: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients with claudication at baseline were at lower risk for MAEs compared with RC 4-5 and RC 6 patients during the 36-month follow-up. Vascular QoL improved from baseline and persisted up to 36 months in all patients.

CONCLUSION: Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. These results provide important point estimates for midterm outcomes after modern endovascular interventions for PAD.

PURPOSE: To examine nationwide variations in inpatient use of drug-coated balloons (DCBs) for treating femoropopliteal segment occlusive disease and whether DCBs are associated with reduced early out-of-hospital health care utilization.

MATERIALS AND METHODS: The study included 24,022 patients who survived hospitalization for femoropopliteal revascularization using DCB angioplasty (n=7850) or uncoated balloon angioplasty (n=16,172) in the 2016-2017 Nationwide Readmissions Database. Differences in patient, hospitalization, and institutional characteristics were compared between treatment strategies. Adjusted logistic regression models were used to examine differences in 6-month rates of readmission, amputation, and repeat intervention. Results are presented as the odds ratio (OR) and 95% confidence interval (CI).

RESULTS: Patients treated with DCBs had a higher prevalence of chronic limb-threatening ischemia, diabetes, hypertension, and tobacco use. Revascularization with a DCB was associated with shorter hospitalizations, lower median hospitalization costs, and fewer inpatient lower extremity amputations. Readmissions at 6 months were decreased in patients treated with DCBs compared with uncoated balloon angioplasty (OR 0.90, 95% CI 0.83 to 0.98, p=0.014). The most common reasons for readmission were complications related to procedures (15.4%) and diabetes (15.4%). Compared to patients treated with DCBs, patients treated with uncoated balloon angioplasty were more often readmitted with early procedure-related complications (13.3% vs 17.5%). There were no between-group differences in readmission for sepsis, myocardial infarction, or congestive heart failure.

CONCLUSION: DCBs are less often used compared to uncoated balloons during inpatient femoropopliteal procedures. While DCB utilization is associated with more severe comorbidities and advanced peripheral artery disease, readmission rates are decreased through the first 6 months.

BACKGROUND: Whether HIV infection is associated with differences in clinical outcomes among people hospitalized with COVID-19 is uncertain.

OBJECTIVE: To evaluate the impact of HIV infection on COVID-19 outcomes among hospitalized patients.

METHODS: Using the American Heart Association's COVID-19 Cardiovascular Disease registry, we used hierarchical mixed effects models to assess the association of HIV with in-hospital mortality accounting for patient demographics and comorbidities and clustering by hospital. Secondary outcomes included major adverse cardiac events (MACE), severity of illness, and length of stay (LOS).

RESULTS: The registry included 21,528 hospitalization records of people with confirmed COVID-19 from 107 hospitals in 2020, including 220 people living with HIV (PLWH). PLWH were younger (56.0+/-13.0 versus 61.3+/-17.9 years old) and more likely to be male (72.3% vs 52.7%), Non-Hispanic Black (51.4% vs 25.4%), on Medicaid (44.5% vs 24.5), and active tobacco users (12.7% versus 6.5%).Of the study population, 36 PLWH (16.4%) had in-hospital mortality compared with 3,290 (15.4%) without HIV (Risk ratio 1.06, 95%CI 0.79-1.43; risk difference 0.9%, 95%CI -4.2 to 6.1%; p=0.71). After adjustment for age, sex, race, and insurance, HIV was not associated with in-hospital mortality (aOR 1.13; 95%CI 0.77-1.6; p 0.54) even after adding body mass index and comorbidities (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91), severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86), or LOS (aOR 1.03; 95% CI 0.76-1.66, p=0.21).

CONCLUSION: HIV was not associated with adverse outcomes of COVID-19 including in-hospital mortality, MACE, or severity of illness.

CONDENSED ABSTRACT: We studied 21,528 patients hospitalized with COVID-19 at 107 hospitals in AHA's COVID-19 registry to examine the association between HIV and COVID-19 outcomes. More patients with HIV were younger, male, non-Hispanic Black, on Medicaid and current smokers. HIV was not associated with worse COVID-19 in-hospital mortality (Risk ratio 1.06, 95%CI 0.79-1.43; p=0.71) even after adjustment (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was also not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91) or severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86. Our findings do not support that HIV is a major risk factor for adverse COVID-19 outcomes.

IMPORTANCE: After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI).

OBJECTIVE: To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a PCI to a nonculprit lesion within 45 days of the index procedure.

EXPOSURES: Multivessel PCI, defined as placement of coronary stents in 2 or more major epicardial vessels or the staged placement of 1 or more coronary stents in a major epicardial vessel distinct from the index culprit vessel, within 45 days of the index PCI.

MAIN OUTCOMES AND MEASURES: Outcomes included the proportional use of MV PCI among STEMI admissions with MV disease, and the timing of MV PCI (an index procedure, a staged procedure during index hospitalization, or a postdischarge procedure within 45 days).

RESULTS: Among 359 879 admissions with STEMI and MV disease, MV PCI was performed in 38.5% (n = 138 380; mean [SD] age of patients, 62.3 [12.3] years; 102 266 men [73.9%]) within 45 days. Of those receiving MV PCIs, 30.8% (n = 42 629) had a procedure performed during the index procedure, 31.6% (n = 43 696) as a staged procedure during the index hospitalization, and 37.6% (n = 52 055) within 45 days of discharge. Complete revascularization of all diseased arteries was performed in 76.2% (n = 105 389). From the third quarter of 2009 to the second quarter of 2013, MV PCI use declined by 10%, from 42.7% (3230 of 7572 cases) to a nadir of 32.7% (3386 of 10 342 cases), followed by an increase to 44.0% (5062 of 11 497 cases) by the fourth quarter of 2017. During this time, there was a 13.6% decline in use of postdischarge staged MV PCI (from 23.4% of STEMI cases [1772 of 7572 cases] in the third quarter of 2009 to 9.9% [1094 of 11 171 cases] in the fourth quarter of 2014) and an 12.5% increase in MV PCI performed during the index admission (from 19.3% [1458 of 7572 cases] in the third quarter of 2009 to 31.8% [3557 of 11 171 cases] in the first quarter of 2018). Multivessel PCI use varied substantially across institutions, with a median use of 37.9% (interquartile range, 30.0%-46.5%).

CONCLUSIONS AND RELEVANCE: In this large, nationwide analysis, MV PCI use for patients with STEMI has been increasing through early 2018 but was used in the minority of patients and with wide variability across US institutions. The adoption of new trial results into guidelines and practice may further promote the growth of MV PCI.

AIMS: Persons living with HIV (PLWH) have increased cardiovascular mortality, which may in part be due to differences in the management of acute coronary syndromes (ACS). The purpose of this study was to compare the in-hospital and post-discharge management and outcomes of ACS among persons with and without HIV.

METHODS AND RESULTS: This was a retrospective cohort study using data from Symphony Health, a data warehouse. All patients admitted between 1 January 2014 and 31 December 2016 with ACS were identified by International Classification of Diseases billing codes. Multivariate logistic regression models were used to examine in-hospital, 30-day and 12-month event rates between groups. A total of 1 125 126 individuals were included, 6612 (0.59%) with HIV. Persons living with HIV were younger (57.4 ± 10.5 vs. 67.4 ± 12.9 years, P< 0.0001) and had more medical comorbidities. Acute coronary syndrome type did not differ significantly with HIV status. Persons living with HIV were less likely to undergo coronary angiography (35.2% vs. 37.2%, adjusted OR 0.87, 95% CI 0.83-0.92, P < 0.0001), and those with both HIV and STEMI underwent fewer drug-eluting stents (60.1% vs. 68.5%, adjusted OR 0.81, 95% CI 0.68-0.96, P = 0.016). Persons living with HIV had higher adjusted rates of inpatient mortality (OR 1.29, 95% CI 1.15-1.44; P < 0.0001), 30-day readmission (OR 1.18, 95% CI 1.09-1.27; P < 0.0001) and 12-month mortality (OR 1.32, 95% CI 1.22-1.44; P < 0.0001). Twelve months following discharge, PLWH filled cardiac medications at lower rates.

CONCLUSION: In a contemporary cohort of persons hospitalized for ACS, PLWH received less guideline-supported interventional and medical therapies and had worse clinical outcomes. Strategies to optimize care are warranted in this unique population.

The desire for an even skin tone pervades all cultures and regions of the world. Uniform skin color is considered a sign of beauty and youth. Pigmentation abnormalities can arise idiopathically with genetic predetermination, with injury and environmental exposures, and with advancing age, and can, therefore, be distressing to patients, leading them to seek a variety of treatments with professional assistance. In this short report, we describe the trends in the use of prescription lightening creams, particularly in patients with darker skin types residing in the US. Amongst 404 participants, skin hyperpigmentation had a moderate effect on patients' quality of life, and the most common diagnosis associated with the use of a prescription product was melasma (60.8%). The most common agent prescribed was hydroquinone (62.9%), followed by triple combination cream (31.4%). It is the dermatologist's duty to gauge the effect of the pigmentation disease on patients' life in order to counsel, tailor, and decide on the most appropriate treatment option.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease associated with high rates of morbidity and mortality. Symptomatic PAD typically presents with claudication, and symptom severity strongly associates with reduced health-related quality of life (HRQoL). Existing treatment strategies for PAD are aimed at reducing symptom severity and improving functional outcomes. However, there is a need to incorporate patient-reported outcome measures (PROMs) into PAD treatment and research in order to provide more patient-centered care. This review will discuss the impact of PAD on HRQoL, existing PROMs available to assess PAD-related HRQoL, utilization of PROMs in research studies and registries, and challenges and solutions related to the integration of PROMs into research and clinical settings.

Patients with peripheral artery disease (PAD) face a range of treatment options to improve survival and quality of life. An evidence-based shared decision-making tool (brochure, website, and recorded patient vignettes) for patients with new or worsening claudication symptoms was created using mixed methods and following the International Patient Decision Aids Standards (IPDAS) criteria. We reviewed literature and collected qualitative input from patients (n = 28) and clinicians (n = 34) to identify decisional needs, barriers, outcomes, knowledge, and preferences related to claudication treatment, along with input on implementation logistics from 59 patients and 27 clinicians. A prototype decision aid was developed and tested through a survey administered to 20 patients with PAD and 23 clinicians. Patients identified invasive treatment options (endovascular or surgical revascularization), non-invasive treatments (supervised exercise therapy, claudication medications), and combinations of these as key decisions. A total of 65% of clinicians thought the brochure would be useful for medical decision-making, an additional 30% with suggested improvements. For patients, those percentages were 75% and 25%, respectively. For the website, 76.5% of clinicians and 85.7% of patients thought it would be useful; an additional 17.6% of clinicians and 14.3% of patients thought it would be useful, with improvements. Suggestions were incorporated in the final version. The first prototype was well-received among patients and clinicians. The next step is to implement the tool in a PAD specialty care setting to evaluate its impact on patient knowledge, engagement, and decisional quality. ClinicalTrials.gov Identifier: NCT03190382.