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.

Association of sleep apnea with outcomes in peripheral artery disease: Insights from the PORTRAIT study.

BACKGROUND: Sleep apnea is a predictor of adverse cardiovascular outcome in many cardiovascular diseases but whether it is associated with worse health status outcomes or mortality in peripheral artery disease (PAD) is unknown. METHODS: PORTRAIT is an international (US, Netherlands, Australia) prospective PAD registry that consecutively enrolled patients who presented with new-onset or recent exacerbations of PAD symptoms to any of 16 vascular specialty clinics. Health status was assessed upon presentation and at 12 months with the disease-specific Peripheral Artery Questionnaire (PAQ). Higher PAQ scores indicate better health status. A sequentially-adjusted hierarchical linear regression model examined the association between sleep apnea and 1-year PAQ symptoms, quality of life, and summary scores. Five-year survival curves by comorbid sleep apnea status for US patients were compared using the log-rank test. RESULTS: The mean age of the 1204 PORTRAIT participants was 67.6 ± 9.4 years with 37.5% women and 8.3% (n = 100) having sleep apnea. Patients with sleep apnea were more likely to be from the US, more sedentary, and to have diabetes, obesity, coronary disease, more depressive symptoms and a history of prior peripheral interventions. Paradoxically, they also had higher ankle-brachial indices, but lower PAQ Summary scores at presentation and 12 months (41.2 ± 22.0 vs. 49. 9± 21.6 and 58.6 ± 27.9 vs. 71.3 ± 24.9, respectively, p = <0.05). The association between sleep apnea and 1-year health status persisted after multivariable adjustment, but there were no differences in all-cause mortality over 5 years (28.0% vs. 23.4%, p = 0.76). CONCLUSION: In patients presenting with PAD, comorbid sleep apnea is independently associated with worse health status over time. Future studies should test whether better treatment of sleep apnea can improve the health status of patients with PAD. CLINICAL TRIAL REGISTRATION: NCT01419080.

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.

The LACE Index: A Predictor of Mortality and Readmission in Patients With Acute Myocardial Infarction.

INTRODUCTION: Improving patient outcomes after acute myocardial infarction (AMI) may be facilitated by identifying patients at a high risk of adverse events before hospital discharge. We aimed to determine the accuracy of the LACE (Length of stay, Acuity, Comorbidities, Emergency presentations within prior 6 months) index score (a prediction tool) for predicting 30-day all-cause mortality and readmission rates (independently and combined) in South Australian AMI patients who had an angiogram. METHODS: All consecutive AMI patients enrolled in the Coronary Angiogram Database of South Australia Registry at two major tertiary hospitals and discharged alive between July 2016 to June 2017. A LACE score was calculated for each patient, and receiver operating characteristic curve analysis was performed. RESULTS: Analysis of registry patients found a 30-day unplanned readmission rate of 11.8% and mortality rate of 0.7%. Moreover, the LACE index was a moderate predictor (C-statistic = 0.62) of readmissions in this cohort, and a score ≥10 indicated moderate discriminatory capacity to predict 30-day readmissions. CONCLUSION: The LACE index shows moderate discriminatory capacity to predict 30-day readmissions and mortality. A cut-off score of nine to optimize sensitivity may assist clinicians in identifying patients at a high risk of adverse outcomes.

Association of perceived stress with health status outcomes in patients with peripheral artery disease.

OBJECTIVE: To assess association of chronic self-perceived stress with health status outcomes of patients with peripheral artery disease. METHODS: The PORTRAIT study is a prospective registry that enrolled 1275 patients with symptoms of peripheral artery disease across 16-sites in US, Netherlands, and Australia from June 2011 to December 2015. Demographics, comorbidities and diagnostic information was abstracted from chart review. Self-perceived stress was assessed using the 4-item perceived stress scale at baseline, 3- and 6-month follow-up. Scores range from 0 to 16 with higher scores indicating greater stress. Sum scores were calculated at each time point and averaged to quantify average exposure to stress from enrollment through 6 months. Disease-specific health status were assessed at baseline and 12-months using the peripheral artery disease questionnaire summary score. RESULTS: The mean age of the analytical cohort (n = 1060) was 67.7 ± 9.3 years, 37.1% were females, and 82.3% were white. Comorbidities were highly prevalent with 80.9% having hypertension, 32.6% having diabetes, and 36.4% being smokers. In models adjusted for demographics, comorbidities, disease severity and socioeconomic status, having a higher average stress score was associated with poorer recovery (from baseline) in peripheral artery disease questionnaire summary score at 12-months (-1.4 points per +1-point increase in averaged 4-point perceived stress score, 95% CI -2.1, -0.6 p < 0.001). CONCLUSION: In patients with peripheral artery disease, experiencing higher chronic stress throughout the 6-months following their diagnosis, was independently associated with poorer recovery in 12-month disease-specific health status outcomes. (ClinicalTrial.gov identifier: NCT01419080).

Frequency, trends and institutional variation in 30-day all-cause mortality and unplanned readmissions following hospitalisation for heart failure in Australia and New Zealand.

AIMS: National 30-day mortality and readmission rates after heart failure (HF) hospitalisations are a focus of US policy intervention and yet have rarely been assessed in other comparable countries. We examined the frequency, trends and institutional variation in 30-day mortality and unplanned readmission rates after HF hospitalisations in Australia and New Zealand. METHODS AND RESULTS: We included patients >18 years hospitalised with HF at all public and most private hospitals from 2010-15. The primary outcomes were the frequencies of 30-day mortality and unplanned readmissions, and the institutional risk-standardised mortality rate (RSMR) and readmission rate (RSRR) evaluated using separate cohorts. The mortality cohort included 153 592 patients (mean age 78.9 ± 11.8 years, 51.5% male) with 16 442 (10.7%) deaths within 30 days. The readmission cohort included 148 704 patients (mean age 78.6 ± 11.9 years, 51.7% male) with 33 158 (22.3%) unplanned readmission within 30 days. In 392 hospitals with at least 25 HF hospitalisations, the median RSMR was 10.7% (range 6.1-17.3%) with 59 hospitals significantly different from the national average. Similarly, in 391 hospitals with at least 25 HF hospitalisations, the median RSRR was 22.3% (range 17.7-27.1%) with 24 hospitals significantly different from the average. From 2010-15, the adjusted 30-day mortality [odds ratio (OR) 0.991/month, 95% confidence interval (CI) 0.990-0.992, P < 0.01] and unplanned readmission (OR 0.998/month, 95% CI 0.998-0.999, P < 0.01) rates declined. CONCLUSION: Within 30 days of a HF hospitalisation, one in 10 patients died and almost a quarter of those surviving experienced an unplanned readmission. The risk of these outcomes varied widely among hospitals suggesting disparities in HF care quality. Nevertheless, a substantial decline in 30-day mortality and a modest decline in readmissions occurred over the study period.

The Association between Sleep Duration and Quality with Readmissions: An Exploratory Pilot-Study among Cardiology Inpatients.

Background: Readmissions within 30 days of discharge are prominent among patients with cardiovascular disease. Post hospital syndrome hypothesizes that sleep disturbance during the index admission contributes to an acquired transient vulnerability, leading to increased risk of readmission. This study evaluated the association of in-hospital sleep (a) duration and (b) quality with 30-day all-cause unplanned readmission. Methods: This prospective observational cohort study included patients admitted to the coronary care unit of a South Australian hospital between 2016-2018. Study participants were invited to wear an ActiGraph GT3X+ for the duration of their admission and for two weeks post-discharge. Validated sleep and quality of life questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), were administered. Readmission status and questionnaires were assessed at 30 days post-discharge via patient telephone interview and a review of hospital records. Results: The final cohort consisted of 75 patients (readmitted: n = 15, non-readmitted: n = 60), of which 72% were male with a mean age 66.9 ± 13.1 years. Total sleep time (TST), both in hospital (6.9 ± 1.3 vs. 6.8 ± 2.9 h, p = 0.96) and post-discharge (7.4 ± 1.3 h vs. 8.9 ± 12.6 h, p = 0.76), was similar in all patients. Patient's perception of sleep, reflected by PSQI scores, was poorer in readmitted patients (9.13 ± 3.6 vs. 6.4 ± 4.1, p = 0.02). Conclusions: Although an association between total sleep time and 30-day readmission was not found, patients who reported poorer sleep quality were more likely to be readmitted within 30 days. This study also highlighted the importance of improving sleep, both in and out of the hospital, to improve the outcomes of cardiology inpatients.

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.

Mental health concerns in patients with symptomatic peripheral artery disease: Insights from the PORTRAIT registry.

OBJECTIVES: To document the prevalence and patient profiles of mental health concerns in patients with peripheral artery disease (PAD) seen in the vascular specialty setting. METHODS: In a cohort of 1275 patients presenting to 16 specialty clinics with new or worsening claudication, symptoms of depression, anxiety, and stress were quantified in 957 patients. The Patient Health Questionnaire-8 (PHQ-8), Generalized Anxiety Disorder scale-2 (GAD-2), and Perceived Stress Scale-4 (PSS-4) were assessed for mental health concerns at the initial PAD work-up and repeated 12 months later. PHQ-8 ≥ 10, GAD-2 ≥ 3 and PSS-4 ≥ 6 were considered significant for depression, anxiety and stress respectively. Patient characteristics were compared in groups divided by presence of 0, 1, 2 or all 3 mental health concerns. RESULTS: On the initial office visit, 336/957 (35%) of patients had high levels of at least one of the three mental health concerns. At both baseline and 12 months, high levels of perceived stress were most often reported (28.7% and 17.5% respectively), followed by symptoms of depression (14.1% and 8.9%) and then anxiety (8.3% and 5.7%). Patients with mental health concerns were more often female, younger, had more financial strain, less social support, and worse perceived health status. CONCLUSIONS: Mental health concerns, particularly stress, are highly prevalent in patients with PAD, especially upon first presenting with new or worsening symptoms. The role of stress and how it may impede successful PAD management and impact subsequent outcomes warrants further investigation.

Readmissions following hospitalisations for cardiovascular disease: a scoping review of the Australian literature.

Objective International studies suggest high rates of readmissions after cardiovascular hospitalisations, but the burden in Australia is uncertain. We summarised the characteristics, frequency, risk factors of readmissions and interventions to reduce readmissions following cardiovascular hospitalisation in Australia. Methods A scoping review of the published literature from 2000-2016 was performed using Medline, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases and relevant grey literature. Results We identified 35 studies (25 observational, 10 reporting outcomes of interventions). Observational studies were typically single-centre (11/25) and reported readmissions following hospitalisations for heart failure (HF; 10/25), acute coronary syndrome (7/25) and stroke (6/25), with other conditions infrequently reported. The definition of a readmission was heterogeneous and was assessed using diverse methods. Readmission rate, most commonly reported at 1 month (14/25), varied from 6.3% to 27%, with readmission rates of 10.1-27% for HF, 6.5-11% for stroke and 12.7-17% for acute myocardial infarction, with a high degree of heterogeneity among studies. Of the 10 studies of interventions to reduce readmissions, most (n=8) evaluated HF management programs and three reported a significant reduction in readmissions. We identified a lack of national studies of readmissions and those assessing the cost and resource impact of readmissions on the healthcare system as well as a paucity of successful interventions to lower readmissions. Conclusions High rates of readmissions are reported for cardiovascular conditions, although substantial methodological heterogeneity exists among studies. Nationally standardised definitions are required to accurately measure readmissions and further studies are needed to address knowledge gaps and test interventions to lower readmissions in Australia. What is known about the topic? International studies suggest readmissions are common following cardiovascular hospitalisations and are costly to the health system, yet little is known about the burden of readmission in the Australian setting or the effectiveness of intervention to reduce readmissions. What does this paper add? We found relatively high rates of readmissions following common cardiovascular conditions although studies differed in their methodology making it difficult to accurately gauge the readmission rate. We also found several knowledge gaps including lack of national studies, studies assessing the impact on the health system and few interventions proven to reduce readmissions in the Australian setting. What are the implications for practitioners? Practitioners should be cautious when interpreting studies of readmissions due the heterogeneity in definitions and methods used in Australian literature. Further studies are needed to test interventions to reduce readmissions in the Australians setting.

Institutional Variation in Quality of Cardiovascular Implantable Electronic Device Implantation: A Cohort Study.

Background: Cardiovascular implantable electronic devices (CIEDs) are associated with procedure-related complications, yet little is known about variation in complication rates among institutions that may suggest disparities in care quality. Objective: To assess institutional variation in risk-standardized complication rates (RSCRs) for CIED. Design: Cohort study. Setting: 174 hospitals in Australia and New Zealand, 98 of which implanted at least 25 CIEDs during the study period. Participants: 81 304 patients older than 18 years (mean, 74.7 years [SD, 12.4]; 37.9% female) who received a new CIED (65 711 permanent pacemakers [PPMs] and 15 593 implantable cardioverter-defibrillators [ICDs]) in 2010 to 2015. Measurements: RSCRs and frequencies of major device-related complications during hospitalization or within 90 days of discharge. Results: Of the cohort, 6664 patients (8.2%) had a major complication. Although complication rates were higher for ICDs than PPMs (10.04% vs. 7.76%), 76.5% of all complications were attributable to PPMs (5098 vs. 1566 for ICDs). Among hospitals that implanted at least 25 CIEDs, the median RSCR was 8.1%; however, rates varied from 5.3% to 14.3%, with 22 hospitals identified as having RSCRs that differed significantly from the national average. Similar variation was observed when RSCRs for PPM implantation (n = 96 hospitals) (median RSCR, 7.6% [range, 5.4% to 12.9%]) were considered separately from those for ICD placement (n = 68 hospitals) (median RSCR, 9.7% [range, 6.2% to 16.9%]) and persisted when only elective procedures were assessed (n = 88 hospitals) (median RSCR, 7.4% [range, 4.7% to 13.0%]). Limitation: Possible unmeasured confounding from the use of administrative data. Conclusion: CIED complications are common and vary among hospitals, suggesting institutional variation in CIED care quality. Concerted clinical and policy interventions are needed to address CIED-related complications. These efforts should preferentially target PPMs, because most CIED complications are attributable to these devices. Primary Funding Source: The Hospitals Contribution Fund Research Foundation.

Sex Differences in Acute Complications of Cardiac Implantable Electronic Devices: Implications for Patient Safety.

Background To date, limited population-level studies have examined the impact of sex on the acute complications of cardiac implantable electronic devices ( CIED) , including permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy devices. Methods and Results We studied all patients aged >18 years from 2010 to 2015 who were a resident of Australia or New Zealand, undergoing a new permanent pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy implant. Standardized variables were collected including patient demographic characteristics, primary and secondary diagnoses, procedures performed and discharge status. Diagnoses and procedures were coded as per the International Classification of Diseases, Tenth Revision ( ICD-10) and the Australian Classification of Health Interventions. The primary end point was the incidence of major CIED -related complications in-hospital or within 90 days of discharge, with the effect of sex evaluated using multiple logistic regression. A total of 81 304 new CIED (61 658 permanent pacemakers, 12 097 implantable cardioverter defibrillators, 7574 cardiac resynchronization therapy) implants were included (38% women). Overall, 8.5% of women and 8.0% of men experienced a CIED complication ( P=0.008). Differences between women and men remained significant after adjustment for age, procedural acuity, and comorbidities (odds ratio 1.10, 95% CI: 1.04-1.16, P<0.001). Differences in CIED complication rates were primarily driven by excess rate of in-hospital pleural drainage (1.2% women versus 0.6% men, P<0.001; adjusted odds ratio 1.86, 95% CI: 1.59-2.17, P<0.001) and pericardial drainage (0.3% women versus 0.1% men, P<0.001; adjusted odds ratio 2.17, 95% CI: 1.48-3.18, P<0.001). Conclusions Women are at higher risk of acute CIED complications. Improvements in implant technique and technologies are required to minimize the risk of implant-related complications in women.

PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories): Overview of Design and Rationale of an International Prospective Peripheral Arterial Disease Study.

BACKGROUND: Health status outcomes, including symptoms, functional status, and quality of life, are critically important outcomes from patients' perspectives. The PORTRAIT study (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) was designed to prospectively define health status outcomes and examine associations between patients' characteristics and care to these outcomes among those presenting with new-onset or worsened claudication. METHODS AND RESULTS: PORTRAIT screened 3637 patients with an abnormal ankle-brachial index and new, or worsened, claudication symptoms from 16 peripheral arterial disease (PAD) specialty clinics in the United States, the Netherlands, and Australia between June 2, 2011, and December 3, 2015. Of the 1608 eligible patients, 1275 (79%) were enrolled. Before treatment, patients were interviewed to obtain their demographics, PAD symptoms and health status, psychosocial characteristics, preferences for shared decision-making, socioeconomic, and cardiovascular risk factors. Patients' medical history, comorbidities, and PAD diagnostic information were abstracted from patients' medical records. Serial information about patients' health status, psychosocial, and lifestyle factors was collected at 3, 6, and 12 months by a core laboratory. Follow-up rates ranged from 84.2% to 91%. Clinical follow-up for PAD-related hospitalizations and major cardiovascular events is ongoing. CONCLUSIONS: PORTRAIT systematically collected serial PAD-specific health status data as a foundation for risk stratification, comparative effectiveness studies, and clinicians' adherence to quality-based performance measures. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01419080.