Comparison of mortality and amputation after lower extremity bypass versus peripheral vascular intervention in patients with chronic limb-threatening ischemia and comorbid chronic kidney disease.

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. METHODS: Individuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. CONCLUSIONS: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

Prevalence and Prognostic Importance of Abnormal Positron Emission Tomography Among Asymptomatic Patients With Diabetes Mellitus.

BACKGROUND: Ischemia and reduced global myocardial blood flow reserve (MBFR) are associated with high cardiovascular risk among symptomatic patients with diabetes mellitus (DM). OBJECTIVES: This study aimed to assess the prevalence and prognostic importance of silent ischemia and reduced MBFR among asymptomatic patients with DM. METHODS: This study included 2,730 consecutive patients with DM, without known coronary artery disease (CAD) or cardiomyopathy, who underwent rubidium-82 rest/stress positron emission tomography (PET) myocardial perfusion imaging (MPI) from 2010 to 2016. These patients were followed up for all-cause mortality (n = 461) for a median follow-up of 3 years. Patients were considered asymptomatic if neither chest pain nor dyspnea was elicited. Rates of ischemia, reduced MBFR, and coronary microvascular dysfunction on PET were assessed in both groups. Cox regression was used to define the independent association of abnormal MPI markers with mortality. RESULTS: One-quarter of patients with DM (23.7%; n = 647) were asymptomatic; ischemia was present in 30.5% (n = 197), reduced MBFR in 62.3% (n = 361), and coronary microvascular dysfunction in 32.7% (n = 200). In adjusted analyses, reduced MBFR (HR per 0.1 unit decrease in MBFR: 1.08 [95% CI: 1.03-1.12]; P = 0.001) and reduced ejection fraction (HR per 5% decrease: 1.10 [95% CI: 1.01-1.18]; P = 0.02) were independently prognostic of mortality among asymptomatic patients, but ischemia was not. This was comparable to DM patients with symptoms. Insulin use and older age were significant predictors of reduced MBFR among asymptomatic patients with DM. CONCLUSIONS: In both symptomatic and asymptomatic patients with DM, impairment in MBFR is common and associated with greater mortality risk.

Coronary vascular dysfunction is associated with increased risk of death in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) and coronary vascular dysfunction are common in patients with cardiometabolic disease. Neither the prevalence of coronary vascular dysfunction among patients with PAD nor the prognostic impact with these two conditions present together has been well studied. METHODS: Consecutive patients who underwent PET MPI were analyzed for presence of coronary vascular dysfunction [myocardial blood flow reserve (MBFR) < 2]. Cox regression was used to examine the association of reduced MBFR with mortality in patients with PAD, as well as the association of comorbid MBFR < 2 and PAD with all-cause death. RESULTS: Among 13,940 patients, 1936 (14%) had PAD, 7782 (56%) had MBFR < 2 and 1346 (10%) had both PAD and MBFR < 2. Reduced MBFR was very common (69.5%) and was associated with increased risk of all-cause death (HR 1.69, 95%CI 1.32, 2.16, p < 0.01) in patients with PAD. Patients with both PAD and MBFR < 2, and those with either PAD or reduced MBFR had increased risk of death compared to those with neither condition: PAD + MBFR < 2 [(HR 95%CI), 2.30; 1.97-2.68], PAD + MBFR ≥ 2 (1.37; (1.08-1.72), PAD - MBFR < 2 (1.98; 1.75-2.25), p < 0.001 for all). CONCLUSION: Coronary vascular dysfunction was common in patients with PAD and was associated with increased risk of death.

Obesity prevalence and variability in management practices for patients with symptomatic peripheral artery disease.

Obesity has been associated with poor disease outcomes in patients with lower extremity peripheral arterial disease (PAD). Given evolving treatments for obesity, evaluating its prevalence and treatment practices are key to develop a holistic management of PAD. We aimed to examine prevalence of obesity and variability of management strategies in symptomatic PAD patients enrolled in the international multicenter PORTRAIT registry from 2011 to 2015. Obesity management strategies studied included weight and/or dietary counseling and prescription of weight loss medications (orlistat, lorcaserin, phentermine-topiramate, naltrexone-buproprion, and liraglutide). Use frequency of obesity management strategies were calculated by country and compared across centers using adjusted median odds ratios (MOR). Of 1002 patients included, 36 % had obesity. No patients received weight loss medications. Weight and/or dietary counseling was prescribed in only 20 % of patients with obesity with significant variability in practices between centers (range 0.0-39.7 %; MOR 3.6, 95 % CI 2.04-9.95, p = < 0.001). In conclusion, obesity is a prevalent modifiable comorbidity in PAD that is hardly addressed during PAD management, with significant variability across practices. As obesity prevalence rates are growing, along with treatment modalities to treat it, especially in those with PAD, building systems to integrate systematic evidence-based weight and dietary management strategies in PAD are essential to close this gap in care.

Association of country economy and socioeconomic factors on risk factor control for primary prevention of cardiovascular disease in patients with diabetes mellitus: Insights from the DISCOVER study.

BACKGROUND: We sought to describe global patterns in achievement of risk factor control for primary prevention in patients with T2D and explore the association of country's GNI/capita with risk factor control. METHODS: The DISCOVER study is a prospective, observational study of patients with T2D from 38 countries enrolled at initiation of second-line glucose-lowering therapy. We examined achievement of risk factor control (glycosylated hemoglobin <7%, blood pressure <140/90 mmHg, prescription of a statin) at 3 years among those without optimal control at baseline. Countries were stratified by gross national income (GNI)/capita, from 2017). We examined the impact of country GNI/capita with achievement of risk factor control. FINDINGS: Our cohort included 9613 patients with T2D and without baseline cardiovascular disease (mean age 57.2 ± 8.7 years, 47.9% women). At baseline, 6354/7646 patients (83.1%) had suboptimal glucose control, 3449/9200 patients (37.5%) had suboptimal BP control, and 2800/4221 patients (66.7%) were not on an appropriate statin (sample sizes differed due to missing covariate data). Optimal control at 3 years of follow-up was achieved in 41% (glucose), 56% (blood pressure), and 29% (statins) of patients. There was significant variability in achievement of risk factor control across countries but no association between country GNI/capita with achievement of risk factor control (p > 0.08 for all). INTERPRETATION: In a global, prospective study of patients with T2D, we found that cardiovascular risk factor control achievement was suboptimal despite 3 years of follow-up in specialized health care systems. Neither country-level nor patient-level socioeconomic factors fully explained this finding.

Patient-level and external factors in the use of drug-coated balloons and drug-eluting stents in femoropopliteal endovascular interventions.

OBJECTIVE: Drug-coated balloons (DCB) and drug-eluting stents (DES) have been rapidly adopted for femoropopliteal endovascular interventions due to their favorable patency rates. It is unclear whether choice of using drug coated devices versus bare metal stents (BMS) or plain balloon angioplasty (POBA) as primary treatment in femoropopliteal disease is mostly associated with patient-level factors, safety concerns, or by operator preferences. This study sought to evaluate factors associated with their use in a contemporary dataset. METHODS: All femoropopliteal lesions treated with endovascular interventions between 2016 and 2019 from the Vascular Quality Initiative registry were included. For each procedure, a primary treatment was identified based on the following hierarchy: DES > DCB > BMS > POBA. A hierarchical logistic regression model predicting DCB or DES use included patient-level characteristics, key events (period after Centers for Medicare and Medicaid Services reimbursement change, January 2018 [vs before] and period after Katsanos meta-analysis December 2018 [vs before]), and random effects for site and operator. Operator-level variability for DCB and DES use was summarized with an adjusted median odds ratio (MOR). RESULTS: A total of 57,753 femoropopliteal endovascular procedures were included. Poor functional status (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.90-0.94), prior anticoagulant use (OR, 0.92; 95% CI, 0.87-0.97), higher Rutherford classification (OR, 0.86; 95% CI, 0.84-0.88), chronic kidney disease stage 4 or 5 (OR, 0.92; 95% CI, 0.86-0.98), and the period after the Katsanos meta-analysis publication (OR, 0.3; 95% CI, 0.29-0.32) were associated with a lower odds of DCB or DES use; whereas female sex (OR, 1.12; 95% CI,1.08-1.17), prior lesion treatment (OR, 1.17; 95% CI, 1.11-1.22), diabetes (OR, 1.07; 95% CI, 1.02-1.12), Trans-Atlantic Inter-Society Consensus class B (OR, 1.16; 95% CI, 1.09-1.24) and C (OR, 1.2; 95% CI, 1.12-1.28), and the period after the Centers for Medicare and Medicaid Services reimbursement change (OR, 1.08; 95% CI, 1.03-1.14) were associated with a higher odds of DCB or DES use. Significant variability in use was found across operators (adjusted MOR, 2.70; 95% CI, 2.55-2.85) and centers (adjusted MOR, 2.89; 95% CI, 2.50-3.27). CONCLUSIONS: DCB or DES use in femoropopliteal disease demonstrates wide variability across operators and is linked strongly with external factors, followed by anatomic lesion characteristics and a history of previous interventions. Future work needs to focus on tailoring DCB or DES use to patient and lesion characteristics and to develop appropriate use guidelines integrating these factors.

Prognostic Relationship Between Coronary Artery Calcium Score, Perfusion Defects, and Myocardial Blood Flow Reserve in Patients With Suspected Coronary Artery Disease.

BACKGROUND: Coronary artery calcium score (CACS) is an anatomic measure of calcified atherosclerosis. Myocardial perfusion defects and reduced myocardial blood flow reserve (MBFR) are physiological measures of ischemia and coronary circulatory health. We aimed to assess the relative prognostic importance of MBFR, perfusion defects, and CACS in patients with suspected coronary artery disease. METHODS: A total of 5983 consecutive patients without known history of coronary artery disease or cardiomyopathy, who underwent a CACS and 82Rb positron emission tomography myocardial perfusion imaging between 2010 and 2016, were followed for all-cause death (n=785) over median of 3 years. Prognostic value was assessed using multivariable Cox regression models, and incremental risk discrimination for imaging variables was evaluated by comparing model c-indices after adjusting for clinical risk factors (RF). RESULTS: Mean age was 67.1 years, 60% were female, and 83% were symptomatic. CACS was 0 in 22%, abnormal perfusion in 19%, and MBFR <2 in 53.3%. When added to RF, the model with MBFR had the best fit (c=0.78, P<0.0001). Addition of CACS to model with RF and perfusion (c=0.77) offered modest improvement in discrimination over the model with RF and perfusion (c=0.76, P=0.02). Adding CACS to a model with RF, perfusion, and MBFR did not provide incremental prognostic value (c=0.785 for both, P=0.16). CACS and MBFR both had independent prognostic value in patients with normal and abnormal myocardial perfusion imaging. Even among patients with CACS of 0, MBFR <2 was present in 37.8%, being associated with higher risk of death (hazard ratio per 0.1↓, 1.10 [1.04-1.15]; P<0.001), but perfusion defects were not. CONCLUSIONS: Use of anatomic testing such as CACS of 0 to avoid myocardial perfusion imaging in symptomatic patients could lead to missing microvascular dysfunction in 4 out of 10 patients, a finding associated with a high mortality risk. Higher CACS was independently associated with the risk of death but did not provide incremental prognostic value over positron emission tomography with MBFR.

Relationship Between Myocardial Perfusion Imaging Abnormalities on Positron Emission Tomography and Anginal Symptoms, Functional Status, and Quality of Life.

BACKGROUND: Myocardial perfusion imaging (MPI) identifies abnormalities that occur early in the ischemic cascade leading to angina. Our aim was to study the association between ischemic measures on positron emission tomography MPI and patients' health status; their symptoms, function, and quality of life. METHODS: Health status was collected using the Seattle Angina Questionnaire (SAQ-7, 0-100, higher=better) and Rose Dyspnea Score (RDS) on 1515 outpatients with known or suspected coronary artery disease presenting for clinically indicated pharmacological 82Rb positron emission tomography MPI from July 2018 to July 2019. Adjusted multivariable ordinal regression models were used to assess the association between MPI findings of ischemia and the SAQ physical limitation, angina frequency, quality of life, summary score, and the RDS. RESULTS: The mean SAQ and RDS scores of the cohort (mean age 71.7 years, 55% male, 37.6% prior myocardial infarction or revascularization) were 73.8±28.6 (physical limitation), 87.4±21.7 (angina frequency), 79.0±26.1 (quality of life), 81.3±19.0 (summary score), and 2±2 (RDS). No perfusion, flow or function abnormalities were significantly associated with SAQ angina frequency scores. Low left ventricular ejection fraction reserve (≤0%), low global and regional myocardial blood flow reserve (<2) were independently associated with worse SAQ Physical Limitation score, SAQ summary score, and RDS (30% to 57% greater odds; all P≤0.01), but reversible perfusion defects were not. CONCLUSIONS: Impaired augmentation of left ventricular ejection fraction and myocardial blood flow with stress is associated with significant angina-associated functional limitation, health status, and dyspnea in patients who underwent positron emission tomography MPI, but not the frequency of their angina. Future studies should evaluate whether therapies that improve stress-induced abnormalities in systolic function and myocardial flow may improve patients' health status.

Association of Disease-Specific Health Status With Long-Term Survival in Peripheral Artery Disease.

Background While peripheral artery disease (PAD) is associated with increased cardiovascular morbidity with mortality remaining high and challenging to predict, accurate understanding of serial PAD-specific health status around the time of diagnosis may prognosticate long-term mortality risk. Methods and Results Patients with new or worsening PAD symptoms enrolled in the PORTRAIT Registry across 10 US sites from 2011 to 2015 were included. Health status was assessed by the Peripheral Artery Questionnaire (PAQ) Summary score at baseline, 3-month, and change from baseline to 3-month follow-up. Kaplan-Meier using 3-month landmark and hierarchical Cox regression models were constructed to assess the association of the PAQ with 5-year all-cause mortality. Of the 711 patients (mean age 68.8±9.6 years, 40.9% female, 72.7% white; mean PAQ 47.5±22.0 and 65.9±25.0 at baseline and 3-month, respectively), 141 (19.8%) died over a median follow-up of 4.1 years. In unadjusted models, baseline (HR, 0.90 per-10-point increment; 95% CI, 0.84-0.97; P=0.008), 3-month (HR [95% CI], 0.87 [0.82-0.93]; P<0.001) and change in PAQ (HR [95% CI], 0.92 [0.85-0.99]; P=0.021) were each associated with mortality. In fully adjusted models including combination of scores, 3-month PAQ was more strongly associated with mortality than either baseline (3-month HR [95% CI], 0.85 [0.78-0.92]; P<0.001; C-statistic, 0.77) or change (3-month HR [95% CI], 0.79 [0.72-0.87]; P<0.001). Conclusions PAD-specific health status is independently associated with 5-year survival in patients with new or worsening PAD symptoms, with the most recent assessment being most prognostic. Future work is needed to better understand how this information can be used proactively to optimize care.

Real-world antithrombotic treatment variability in patients undergoing peripheral vascular intervention: Insights from the VQI registry.

For those undergoing peripheral vascular interventions (PVI), guidelines indicate the use of dual antiplatelet therapy (DAPT) is reasonable (Class IIb), but recommendations have not reached the highest level of evidence. In the largest effort to date, we found that antithrombotic prescription was dominated by single antiplatelet therapy (SAPT) (51.4%) before PVI, which switched to DAPT (57.7%) following PVI, with some patients still remaining on no therapy (8%). High site variability in prescription rates (median odds ratio: 1.40, 95% confidence interval: 1.32, 1.48) was not much explained by patient and provider factors, revealing a need for the creation and integration of the newest trial data and for interventions at the health system or practice level to help physicians determine the optimal medical therapy following PVI.

Relative Prognostic Significance of Positron Emission Tomography Myocardial Perfusion Imaging Markers in Cardiomyopathy.

BACKGROUND: Rubidium-82 positron emission tomography myocardial perfusion imaging provides measurements of perfusion, myocardial blood flow and reserve (MBFR), and changes in left ventricular ejection fraction (LVEF) at rest and peak stress. Although all of these variables are known to provide prognostic information, they have not been well studied in patients with heart failure due to reduced LVEF. METHODS: Between 2010 and 2016, 1255 consecutive unique patients with LVEF≤40% were included in this study who underwent rubidium-82 positron emission tomography myocardial perfusion imaging and did not have subsequent revascularization within 90 days. Perfusion assessment was scored semiquantitatively, and LVEF reserve (stress-rest LVEF) and global MBFR (stress/rest MBF) were quantified using automated software. Cox proportional hazards models adjusted for 14 clinical and 7 test characteristics were used to define the independent prognostic significance of MBFR on all-cause mortality. RESULTS: Of 1255 patients followed for a mean of 3.2 years, 454 (36.2%) died. After adjusting for clinical variables, the magnitude of fixed and reversible perfusion defects was prognostic of death (P=0.02 and 0.01, respectively), while the rest LVEF was not (P=0.18). The addition of LVEF reserve did not add any incremental value, while the addition of MBFR revealed incremental prognostic value (hazard ratio per 0.1 unit decrease in MBFR=1.08 [95% CI, 1.05-1.11], P<0.001) with fixed and reversible defects becoming nonsignificant (P=0.07 and 0.29, respectively). There was no interaction between MBFR and cause of cardiomyopathy (ischemic versus nonischemic). CONCLUSIONS: In patients with a known cardiomyopathy who did not require early revascularization, reduced MBFR as obtained by positron emission tomography myocardial perfusion imaging is associated with all-cause mortality while other positron emission tomography myocardial perfusion imaging measures were not.

Differential effects of eplerenone versus amlodipine on muscle metaboreflex function in hypertensive humans.

Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post-exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p < .01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post-exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.

Establishing Thresholds for Minimal Clinically Important Differences for the Peripheral Artery Disease Questionnaire.

BACKGROUND: Understanding minimum clinically important differences (MCID) in patient-reported outcomes is essential in interpreting the magnitude of changes in these measures. No MCID from patients' perspectives has ever been published for peripheral artery disease-specific health status assessment tools. The Peripheral Artery Questionnaire (PAQ) is a commonly used, validated peripheral artery disease-specific health status instrument for which we sought to prospectively establish its MCID from patients' perspectives. METHODS AND RESULTS: Patients presenting to vascular clinics with new or worsened claudication in the US cohort of the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry who completed baseline and follow-up PAQ assessments along with the Global Assessment of Functioning scale were included. Mean change in PAQ summary scores from 3- to 6-month follow-up was calculated according to Global Assessment of Functioning category. MCID was defined as the mean difference in scores between those with small improvement or deterioration and those with no change. Multivariable linear regression was used to provide an MCID estimate after adjusting for patients' 3-month PAQ score. Of the 483 patients who completed the Global Assessment of Functioning score at 6 months and who had available 3- and 6-month PAQ assessments, the mean age was 69 years, 42% were female, and 71% were White. The MCIDs for PAQ summary scale improvement and worsening were 8.7 (2.9-14.5) and -11.0 (-18.6 to -3.3), respectively. After multivariable adjustment, these were 8.9 (3.0-14.8) and -11.2 (-18.2 to -4.2), respectively. There was no significant interaction between treatment (invasive versus noninvasive) and Global Assessment of Functioning response (P=0.75). CONCLUSIONS: In patients with new or worsened claudication, a 10-point change in PAQ summary score represents an MCID. This estimate needs external validation and may inform the interpretation of PAQ scores when used as outcomes in clinical trials or in routine clinical care. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01419080.

Physical Activity After Treatment for Symptomatic Peripheral Artery Disease.

The association of invasive versus noninvasive treatment and physical activity level in patients with claudication remains unclear. Participants with claudication were enrolled from US vascular clinics. Treatment was categorized as invasive (surgical or endovascular treatment <3 months of initial visit) versus noninvasive. Self-reported leisure time (LTPA) and work related physical activity (WRPA) (sedentary, mild, moderate/strenuous), and health status (peripheral artery questionnaire summary score [PAQ SS]) was measured at baseline and 12 months. Change in PA was also categorized as increased, decreased, persistent sedentary [reference] and persistent active based on activity status at baseline and 12 months. Multivariable logistic regression assessed the association of treatment with 12-month LTPA and WRPA. Multivariable linear regression examined the association between 12-month change in PA with a 12-month change in PAQ. A total of 196of 656 patients (29.9%) underwent invasive treatment. There was no association between treatment and 12-month LTPA (p = 0.77) or WRPA (p = 0.26). Compared with being persistently sedentary, increased LTPA was associated with increased PAQ SS (OR 11.1 95% CI [4.4 to 17.7], p <0.01). In conclusion, there was no association between invasive treatment and physical activity at follow up despite a greater health status change in the invasive group. As increased physical activity was associated with more health status gains than remaining sedentary, additional ways to improve physical activity levels could potentially improve PAD outcomes.

Stress myocardial perfusion imaging in patients presenting with syncope: Comparison of PET vs. SPECT.

BACKGROUND: The role of myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD) presenting with syncope is controversial. We aimed to determine diagnostic yield of MPI for evaluation of syncope in patients without known CAD, as a function of pre-test patient risk and test modality (PET vs SPECT). METHODS: Between 1/2010 and 12/2016, 1324 consecutive patients presenting with syncope without known CAD underwent MPI with PET (n = 640) or SPECT (n = 684). Rates of abnormal MPI (summed difference score (SDS) > 2 or left ventricular ejection fraction (LVEF) reserve ≤ 0 for PET and SDS > 2 or post-stress LVEF ≤ 45% for SPECT) were determined among patients stratified by pre-test risk. In patients who were referred for coronary angiography, diagnostic yield of obstructive CAD was calculated in the overall cohort as well as in a propensity-matched cohort compared to patients without syncope. RESULTS: Abnormal MPI was noted in 36.5% (201/551) of patients who had PET compared with 13.0% (87/671) who had SPECT (P < 0.001), which is largely related to higher comorbidity burden and greater pre-test CAD risk in the PET population. Among patients who had an abnormal MPI, 8.5% (47/551) with PET and 0.7% (5/671) with SPECT were found to have obstructive CAD if referred for coronary angiography. Patients at intermediate-high pre-test risk had a higher proportion of abnormal MPIs and obstructive CAD as compared to those at low risk in both the PET and SPECT cohorts. The rate of abnormal testing and diagnostic yield of PET MPI was similar and proportionate to pre-test likelihood among matched patients with and without syncope. CONCLUSIONS: Among patients referred for PET MPI with syncope at an intermediate-high pre-test CAD risk, 1 in 3 had an abnormal MPI and 1 in 10 had obstructive CAD. The value of MPI was related to pre-test risk as opposed to the presence of syncope, and MPI testing with PET or SPECT in the low-risk population was low value.

Association of Diabetes Mellitus With Health Status Outcomes in Patients With Peripheral Artery Disease: Insights From the PORTRAIT Registry.

Background Patients with peripheral artery disease (PAD) and coexisting diabetes mellitus (DM) have greater PAD progression and adverse limb events. Our aim was to study whether PAD-specific health status differs by DM. Methods and Results The PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) trial is a 16-center international registry that includes patients with recent exacerbations or new-onset symptomatic PAD presenting to specialty clinics. We assessed PAD-specific health status initially and at 3, 6, and 12 months (Peripheral Artery Questionnaire [PAQ]). We used hierarchical, multivariable, linear regression, and repeated measures analyses to study the association between DM and baseline health status initially and over 3 to 12 months. Models were adjusted for demographics, socioeconomic factors, PAD severity, comorbidities, and psychosocial characteristics. The interaction of DM with PAD revascularization on 3- to 12-month health status was also tested. Of 1204 patients, 398 (33%) had DM (94% type 2). Patients with versus those without DM had lower unadjusted PAQ summary scores at baseline and 3, 6, and 12 months (46.1 versus 50.8, 63.6 versus 68.2, 65.7 versus 71.7, and 65.4 versus 72.6; P≤0.01). In fully adjusted models, the effect of DM on baseline (mean difference, -0.65; 95% CI, -2.86 to 1.56 [P=0.56]) and over 3- to 12-month PAQ summary scores (mean difference, -1.59; 95% CI, -4.06 to 0.88 [P=0.21]) was no longer significant. Twelve-month health status gains following revascularization were similar in both groups (P=0.69). Conclusions Patients with PAD with coexisting DM have poorer health status, mostly explained by the differences in their psychosocial and other comorbidity burden. Patients with PAD and DM versus those without DM experience similar health status benefits following PAD revascularization.

Physical Activity in Patients with Symptomatic Peripheral Artery Disease: Insights from the PORTRAIT Registry.

OBJECTIVE: A physically active lifestyle reduces the risk of cardiovascular events and functional impairment in patients with peripheral artery disease (PAD). There are limited data on the patterns of physical activity in patients with PAD compared between countries. METHODS: Self reported physical activity (sedentary vs. not) was obtained at enrolment, 3, 6, and 12 months in the US and Netherlands' cohorts of the Patient-centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) registry of patients with new or worsening claudication. Multivariable repeated measures using modified Poisson regression analysis compared the proportion of sedentary participants over time between countries to identify factors that attenuate intercountry differences. RESULTS: Of 1 098 participants, 743 (67.7%) and 355 (32.3%) were recruited from the USA and the Netherlands respectively. Compared with the Netherlands, participants from the US were older (mean age 68.6 vs. 65.3 years; p < .001), more obese (41.3% vs. 20.5%; p < .001), and more likely to be female (41.3% vs. 31.4%; p = .002). There were fewer current smokers (30.1% vs. 52.8%; p < .001) and supervised exercise referrals (1.6% vs. 63.9%; p < .001) in the US compared with the Netherlands. US participants were more sedentary at baseline (43.7% vs. 34.1%; p < .001). Sedentary behaviour decreased after three months in both countries, then diverged with an increase in sedentary participants in the USA. Risk of sedentary behaviour was significantly greater in the USA compared with the Netherlands at 12 months, after adjustment of sociodemographic, lifestyle factors, and comorbidities (relative risk [RR] 1.56, 95% confidence interval [CI] 1.08-2.25; p = .020) but was attenuated after accounting for referral to supervised exercise (RR 1.20, 95% CI 0.67-2.16; p = .54). CONCLUSION: Referral to supervised exercise was key in explaining the observed difference in the physical activity levels between patients with PAD in the USA and the Netherlands. Further promotion of supervised exercise for PAD may improve physical activity in patients with PAD and modify cultural norms of inactivity in the US.

Association of Perceived Stress Levels With Long-term Mortality in Patients With Peripheral Artery Disease.

Importance: Identifying modifiable risk factors, such as stress, that could inform the design of peripheral artery disease (PAD) management strategies is critical for reducing the risk of mortality. Few studies have examined the association of self-perceived stress with outcomes in patients with PAD. Objective: To examine the association of high levels of self-perceived stress with mortality in patients with PAD. Design, Setting, and Participants: This cohort study analyzed data from the registry of the Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study, a multicenter study that enrolled patients with new or worsening symptoms of PAD who presented to 16 subspecialty clinics across the US, the Netherlands, and Australia from June 2, 2011, to December 3, 2015. However, the present study included only patients in the US sites because assessments of mortality for patients in the Netherlands and Australia were not available. Data analysis was conducted from July 2019 to March 2020. Exposure: Self-perceived stress was quantified using the 4-item Perceived Stress Scale (PSS-4), with a score range of 0 to 16. A score of 6 or higher indicated high stress in this cohort. Missing scores were imputed using multiple imputation by chained equations with predictive mean matching. Stress was assessed at baseline and at 3-, 6-, and 12-month follow-up. Patients who reported high levels of stress at 2 or more follow-up assessments were categorized as having chronic stress. Main Outcomes and Measures: All-cause mortality was the primary study outcome. Such data for the subsequent 4 years after the 12-month follow-up were obtained from the National Death Index. Results: The final cohort included 765 patients, with a mean (SD) age of 68.4 (9.7) years. Of these patients, 57.8% were men and 71.6% were white individuals. High stress levels were reported in 65% of patients at baseline and in 20% at the 12-month follow-up. In an adjusted Cox proportional hazards regression model accounting for demographics, comorbidities, disease severity, treatment type, and socioeconomic status, exposure to chronic stress during the 12 months of follow-up was independently associated with increased risk of all-cause mortality in the subsequent 4 years (hazard ratio, 2.12; 95% CI, 1.14-3.94; P = .02). Conclusions and Relevance: In thie cohort study of patients with PAD, higher stress levels in the year after diagnosis appeared to be associated with greater long-term mortality risk, even after adjustment for confounding factors. These findings suggest that, given that stress is a modifiable risk factor for which evidence-based management strategies exist, a holistic approach that includes assessment of chronic stress has the potential to improve survival in patients with PAD.

Mobile App to Improve House Officers' Adherence to Advanced Cardiac Life Support Guidelines: Quality Improvement Study.

BACKGROUND: Effective and timely delivery of cardiac arrest interventions during in-hospital cardiac arrest resuscitation is associated with greater survival. Whether a mobile app that provides timely reminders of critical interventions improves adherence to Advanced Cardiovascular Life Support (ACLS) guidelines among house officers, who may lack experience in leading resuscitations, remains unknown. OBJECTIVE: The aim of this study was to assess the impact of a commercially available, dynamic mobile app on house officers' adherence to ACLS guidelines. METHODS: As part of a quality improvement initiative, internal medicine house officers were invited to participate and randomized to lead 2 consecutive cardiac arrest simulations, one with a novel mobile app and one without a novel mobile app. All simulations included 4 cycles of cardiopulmonary resuscitation with different cardiac arrest rhythms and were video recorded. The coprimary end points were chest compression fraction and number of correct interventions in each simulation. The secondary end point was incorrect interventions, defined as interventions not indicated by the 2015 ACLS guidelines. Paired t tests compared performance with and without the mobile app. RESULTS: Among 53 house officers, 26 house officers were randomized to lead the first simulation with the mobile app, and 27 house officers were randomized to do so without the app. Use of the mobile app was associated with a higher number of correct ACLS interventions (out of 7; mean 6.2 vs 5.1; absolute difference 1.1 [95% CI 0.6 to 1.6]; P<.001) as well as fewer incorrect ACLS interventions (mean 0.3 vs 1.0; absolute difference -0.7 [95% CI -0.3 to -1.0]; P<.001). Simulations with the mobile app also had a marginally higher chest compression fraction (mean 90.9% vs 89.0%; absolute difference 1.9% [95% CI 0.6% to 3.4%]; P=.007). CONCLUSIONS: This proof-of-concept study suggests that this novel mobile app may improve adherence to ACLS protocols, but its effectiveness on survival in real-world resuscitations remains unknown.