Association of Patient Reported Outcomes With Caregiver Burden in Older Patients With Advanced Heart Failure: Insights From the SUSTAIN-IT Study.

BACKGROUND: Caregivers of patients with advanced heart failure may experience burden in providing care, but whether changes in patient health status are associated with caregiver burden is unknown. METHODS: This observational study included older patients (60-80 years old) receiving advanced surgical heart failure therapies and their caregivers at 13 US sites. Patient health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (range, 0-100; higher scores are better). Caregiver burden was assessed using the Oberst Caregiving Burden Scale, which measures time on task (OCBS-time) and task difficulty (OCBS-difficulty; range, 1-5; lower scores are better). Measurements occurred before surgery and 12 months after in 3 advanced heart failure cohorts: patients receiving long-term left ventricular assist device support; heart transplantation with pretransplant left ventricular assist device support; and heart transplantation without pretransplant left ventricular assist device support. Multivariable linear regression was used to identify predictors of change in OCBS-time and OCBS-difficulty at 12 months. RESULTS: Of 162 caregivers, the mean age was 61.0±9.4 years, 139 (86%) were female, and 140 (86%) were the patient's spouse. At 12 months, 99 (61.1%) caregivers experienced improved OCBS-time, and 61 (37.7%) experienced improved OCBS-difficulty (versus no change or worse OCBS). A 10-point higher baseline 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (ß=-0.09 [95% CI, -0.14 to -0.03]; P<0.001) and OCBS-difficulty (ß=-0.08 [95% CI, -0.12 to -0.05]; P<0.001). Each 10-point improvement in the 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (ß=-0.07 [95% CI, -0.12 to -0.03]; P=0.002) and OCBS-difficulty (ß=-0.09 [95% CI, -0.12 to -0.06]; P<0.001). CONCLUSIONS: Among survivors at 12 months, baseline and change in patient health status were associated with subsequent caregiver time on task and task difficulty in dyads receiving advanced heart failure surgical therapies, highlighting the potential for serial 12-item Kansas City Cardiomyopathy Questionnaire assessments to identify caregivers at risk of increased burden. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02568930.

Generalizable Approach to Quantifying Guideline-Directed Medical Therapy.

BACKGROUND: Quantifying guideline-directed medical therapy (GDMT) intensity is foundational for improving heart failure (HF) care. Existing measures discount dose intensity or use inconsistent weighting. METHODS: The Kansas City Medical Optimization (KCMO) score is the average of total daily to target dose percentages for eligible GDMT, reflecting the percentage of optimal GDMT prescribed (range, 0-100). In Change the Management of Patients With HF, we computed KCMO, HF collaboratory (0-7), and modified HF Collaboratory (0-100) scores for each patient at baseline and for 1-year change in established GDMT at the time (mineralocorticoid receptor antagonist, ß-blocker, ACE [angiotensin-converting enzyme] inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor). We compared baseline and 1-year change distributions and the coefficient of variation (SD/mean) across scores. RESULTS: Among 4532 patients at baseline, mean KCMO, HF collaboratory, and modified HF Collaboratory scores were 38.8 (SD, 25.7), 3.4 (1.7), and 42.2 (22.2), respectively. The mean 1-year change (n=4061) for KCMO was -1.94 (17.8); HF collaborator, -0.11 (1.32); and modified HF Collaboratory, -1.35 (19.8). KCMO had the highest coefficient of variation (0.66), indicating greater variability around the mean than the HF collaboratory (0.49) and modified HF Collaboratory (0.53) scores, reflecting higher resolution of the variability in GDMT intensity across patients. CONCLUSIONS: KCMO measures GDMT intensity by incorporating dosing and treatment eligibility, provides more granularity than existing methods, is easily interpretable (percentage of ideal GDMT), and can be adapted as performance measures evolve. Further study of its association with outcomes and its usefulness for quality assessment and improvement is needed.

Variation in Health Status With Invasive vs Conservative Management of Chronic Coronary Disease.

BACKGROUND: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients. OBJECTIVES: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making. METHODS: One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status). RESULTS: Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making. CONCLUSIONS: In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Versus Aspiration for Tissue Sampling Adequacy for Molecular Testing in Pancreatic Ductal Adenocarcinoma.

BACKGROUND AND AIMS: There is limited literature on sample adequacy for molecular testing in pancreatic ductal adenocarcinoma obtained via endoscopic ultrasound (EUS) fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). We aimed to compare these two modalities regarding sample adequacy for molecular and genomic sequencing. METHODS: We reviewed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke's Hospital from 2018 to 2021. The patients were categorized based on the method of EUS tissue acquisition, specifically FNA or FNB. A comprehensive evaluation was conducted for all cases by cytotechnologists. RESULTS: Out of 132 patients who underwent EUS-guided biopsies, 76 opted for FNA, 48 opted for FNB, and 8 opted for a combination of both. The average number of passes required for FNB and FNA was 2.58 ± 1.06 and 2.49 ± 1.07, respectively (p = 0.704), indicating no significant difference. Interestingly, 71.4% (35) of FNB-obtained samples were deemed adequate for molecular testing, surpassing the 32.1% (26) adequacy observed with FNA (p < 0.001). Additionally, 46.4% (26) of FNB-obtained samples were considered adequate for genomic testing, a notable improvement over the 23.8% (20) adequacy observed with FNA (p = 0.005). CONCLUSION: Although the number of passes required for cytologic diagnosis did not differ significantly between EUS-FNB and EUS-FNA, the former demonstrated superiority in obtaining samples adequate for molecular testing. Tumor surface area and cellularity were crucial parameters in determining sample adequacy for molecular testing, irrespective of the chosen tissue acquisition modality.

Early Longitudinal Change in Heart Failure Health Status Following Initiation of Canagliflozin.

BACKGROUND: Sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy improves health status in heart failure (HF). There is insufficient description regarding the timing, rate, and extent of the health status changes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) after initiation of SGLT2is. OBJECTIVES: The authors sought to model the association of canagliflozin treatment with rates of change in HF symptom status in HFpEF and HFrEF. METHODS: Study participants with HFrEF and HFpEF were treated with either canagliflozin 100 mg or placebo for 12 weeks. The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) was assessed at baseline and at 2, 4, 6, and 12 weeks. Longitudinal modeling assessed slope of KCCQ change across the study. RESULTS: Among 448 individuals with HF (181 with HFrEF and 267 with HFpEF), participants with HFpEF had lower baseline KCCQ-TSS scores than those with HFrEF (54 ± 21 vs 64 ± 20). Modeling demonstrated initial rapid improvement in KCCQ-TSS in both HF groups, with deceleration over the next 4 to 6 weeks. The rate of change was greater among HFpEF participants (0.7 points/day; 95% CI: 0.3-1.1 points/day) than HFrEF participants (ΔKCCQ-TSS/day = 0.5; 95% CI: 0.1-1.0 points/day) randomized to canagliflozin, but these differences were not statistically significant (0.2 points/day; 95% CI: -0.4 to 0.7 points/day; P = 056). CONCLUSIONS: After canagliflozin therapy, regardless of EF, modeling shows the KCCQ-TSS improves rapidly with the greatest improvements occurring within the first weeks of treatment. These results have implications for clinical use of SGLT2is and may be useful in the design of trials examining impact of these agents on health status in HF. (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure [CHIEF-HF]; NCT04252287).

Physician Estimates and Patient-Reported Health Status in Atrial Fibrillation.

Importance: A primary objective in managing atrial fibrillation (AF) is to optimize patients' health status, which can be done only if physicians accurately quantify the outcomes associated with AF in patients' lives. Objective: To explore physicians' estimation of the health status of patients with AF and its association with subsequent care and outcomes. Design, Setting, and Participants: A multicenter, prospective cohort study was conducted in 2 outpatient practices in Tokyo, Japan. Participants included patients with newly diagnosed AF or those referred for initial treatment of AF at outpatient practices and treating physicians from November 8, 2018, to April 1, 2020. Data analysis was performed from December 22, 2022, to July 7, 2023. Exposures: Participating patients completed the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire, a 20-item tool covering 4 domains with a 7-point Likert scale; 3 domains (symptoms, daily activities, and treatment concerns) were used in this study. Blinded to patients' responses, treating physicians answered a 3-item questionnaire quantifying each patient's AFEQT domain with a single item. Patients' mean Likert scale responses within each AFEQT domain were subtracted from the physicians' assessments so that higher scores (≥0.5 points) indicate physician underestimation, while lower scores (≤0.5 points) indicate physician overestimation of the health status of patients with AF. Main Outcomes and Measures: The independent association of physician-patient concordance with treatment escalation (alteration or initiation of antiarrhythmic drugs, cardioversion, or catheter ablation) and 1-year adjusted changes in AFEQT scores. Results: Among 330 patients (238 [72.1%] men; mean [SD] age, 67.9 [11.9] years; 163 [49.4%] with paroxysmal AF), physicians correctly estimated health status in 112 patients (33.9%), underestimated it in 42 patients (12.7%), and overestimated it in 176 patients (53.3%). Treatment escalation occurred in 63.6% of patients whose health status was correctly estimated, 47.6% of those whose health status was underestimated, and 66.3% of patients whose health status was overestimated. After multivariable adjustment, underestimation of health status was independently associated with less treatment escalation (adjusted odds ratio, 0.43; 95% CI, 0.20-0.90) and less frequent AFEQT overall summary score improvement at 1 year (underestimated, 2.5 [95% CI, -1.6 to 6.7] vs correctly and overestimated health status, 8.4 [95% CI, 7.0-9.9] points; P = .01). Conclusions and Relevance: In this cohort study, physician underestimation of the health status of patients with AF was common and associated with less aggressive treatment and less health status improvement at 1 year.

Association Between Cardiovascular Event Type and Smoking Cessation Rates Among Outpatients With Atherosclerotic Cardiovascular Disease: Insights From the NCDR PINNACLE Registry.

BACKGROUND: It is unclear how the type of an atherosclerotic cardiovascular disease (ASCVD) event potentially influences patients' likelihood of smoking cessation. METHODS: Using 2013 to 2018 data from the US based National Cardiovascular Data Registry Practice Innovation and Clinical Excellence outpatient cardiac registry, we identified patients who were current smokers at a clinic visit and followed them over time for a subsequent ASCVD event. Self-reported smoking status was assessed at each consecutive visit and used to determine smoking cessation after each interim ASCVD event (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke/transient ischemic attack, peripheral artery disease). We constructed separate multivariable Cox models with nonproportional hazards to examine the association of each interim ASCVD event with smoking cessation, compared with not having an interim ASCVD event. We estimated the relative association of ASCVD event type with smoking cessation using contrast tests. Analyses were stratified by presence versus absence of ASCVD at baseline. RESULTS: Across 530 cardiology practices, we identified 1 933 283 current smokers (mean age 62±15, male 54%, ASCVD at baseline 50%). Among the 322 743 patients who had an interim ASCVD event and were still smoking, 41 336 (12.8%) quit smoking by their first subsequent clinic visit, which was higher among those with baseline ASCVD (13.4%) as compared with those without baseline ASCVD (11.5%). Each type of ASCVD event was associated with an increased likelihood of smoking. Patients who had an myocardial infarction, underwent coronary artery bypass graft (hazard ratio, 1.60 [95% CI, 1.55-1.65]), or had a stroke or transient ischemic attack were more likely to quit smoking as compared with those who underwent elective percutaneous coronary intervention or had a new diagnosis of peripheral artery disease (hazard ratio, 1.20 [95% CI, 1.17-1.22]). CONCLUSIONS: Only 13% of patients reported smoking cessation after an ASCVD event, with the type of event being associated with the likelihood of smoking cessation, prompting the need for patient-centered interventions.

TAAR1 agonists improve glycemic control, reduce body weight and modulate neurocircuits governing energy balance and feeding.

OBJECTIVE: Metabolic Syndrome, which can be induced or exacerbated by current antipsychotic drugs (APDs), is highly prevalent in schizophrenia patients. Recent preclinical and clinical evidence suggest that agonists at trace amine-associated receptor 1 (TAAR1) have potential as a new treatment option for schizophrenia. Intriguingly, preclinical tudies have also identified TAAR1 as a novel regulator of metabolic control. Here we evaluated the effects of three TAAR1 agonists, including the clinical development candidate ulotaront, on body weight, metabolic parameters and modulation of neurocircuits implicated in homeostatic and hedonic feeding. METHODS: Effects of TAAR1 agonists (ulotaront, RO5166017 and/or RO5263397) on body weight, food intake and/or metabolic parameters were investigated in rats fed a high-fat diet (HFD) and in a mouse model of diet-induced obesity (DIO). Body weight effects were also determined in a rat and mouse model of olanzapine-, and corticosterone-induced body weight gain, respectively. Glucose tolerance was assessed in lean and diabetic db/db mice and fasting plasma glucose and insulin examined in DIO mice. Effects on gastric emptying were evaluated in lean mice and rats. Drug-induced neurocircuit modulation was evaluated in mice using whole-brain imaging of c-fos protein expression. RESULTS: TAAR1 agonists improved oral glucose tolerance by inhibiting gastric emptying. Sub-chronic administration of ulotaront in rats fed a HFD produced a dose-dependent reduction in body weight, food intake and liver triglycerides compared to vehicle controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in HFD rats switched to ulotaront or RO5263397 treatment compared to those switched to vehicle. Chronic ulotaront administration also reduced body weight and improved glycemic control in DIO mice, and normalized corticosterone-induced body weight gain in mice. TAAR1 activation increased neuronal activity in discrete homeostatic and hedonic feeding centers located in the dorsal vagal complex and hypothalamus with concurrent activation of several limbic structures. CONCLUSION: The current data demonstrate that TAAR1 agonists, as a class, not only lack APD-induced metabolic liabilities but can reduce body weight and improve glycemic control in rodent models. The underlying mechanisms likely include TAAR1-mediated peripheral effects on glucose homeostasis and gastric emptying as well as central regulation of energy balance and food intake.

Body Mass Index and Clinical and Health Status Outcomes in Chronic Coronary Disease and Advanced Kidney Disease in the ISCHEMIA-CKD Trial.

OBJECTIVE: This study aimed to assess whether an obesity paradox (lower event rates with higher body mass index [BMI]) exists in participants with advanced chronic kidney disease (CKD) and chronic coronary disease in the International Study of Comparative Health Effectiveness of Medical and Invasive Approaches (ISCHEMIA)-CKD, and whether BMI modified the effect of initial treatment strategy. METHODS: Baseline BMI was analyzed as both a continuous and categorical variable (< 25, ≥ 25 to < 30, ≥ 30 kg/m2). Associations between BMI and the primary outcome of all-cause death or myocardial infarction (D/MI), and all-cause death, cardiovascular death, and MI individually were estimated. Associations with health status were also evaluated using the Seattle Angina Questionnaire-7, the Rose Dyspnea Scale, and the EuroQol-5D Visual Analog Scale. RESULTS: Body mass index ≥ 30 kg/m2 vs < 25 kg/m2 demonstrated increased risk for MI (hazard ratio [HR] [95% confidence interval] = 1.81 [1.12-2.92]) and for D/MI (HR 1.45 [1.06-1.96]) with a HR for MI of 1.22 (1.05-1.40) per 5 kg/m2 increase in BMI in unadjusted analysis. In multivariate analyses, a BMI ≥ 30 kg/m2 was marginally associated with D/MI (HR 1.43 [1.00-2.04]) and greater dyspnea throughout follow-up (P < .05 at all time points). Heterogeneity of treatment effect between baseline BMI was not evident for any outcome. CONCLUSIONS: In the ISCHEMIA-CKD trial, an obesity paradox was not detected. Higher BMI was associated with worse dyspnea, and a trend toward increased D/MI and MI risk. Larger studies to validate these findings are warranted.

Cardiac Arrest Survival at Emergency Medical Service Agencies in Catchment Areas With Primarily Black and Hispanic Populations.

Importance: Black and Hispanic patients are less likely to survive an out-of-hospital cardiac arrest (OHCA) than White patients. Given the central importance of emergency medical service (EMS) agencies in prehospital care, a better understanding of OHCA survival at EMS agencies that work in Black and Hispanic communities and White communities is needed to address OHCA disparities. Objective: To examine whether EMS agencies serving catchment areas with primarily Black and Hispanic populations (Black and Hispanic catchment areas) have different rates of OHCA survival than agencies serving catchment areas with primarily White populations (White catchment areas). Design, Setting, and Participants: A cohort study including adults with nontraumatic OHCA from January 1, 2015, to December 31, 2019, in the Cardiac Arrest Registry to Enhance Survival was conducted. Data analysis was conducted from August 17, 2022, to July 7, 2023. Exposure: Emergency medical service agencies, categorized as working in catchment areas where the combination of Black and Hispanic residents made up more than 50% of the population or where White residents made up more than 50% of the population. Main Outcomes and Measures: The unit of analysis was the EMS agency. The primary outcome was agency-level risk-standardized survival rates (RSSRs) to hospital admission for OHCA at each EMS agency, which were calculated using hierarchical logistic regression and compared between agencies serving Black and Hispanic and White catchment areas. Whether differences in OHCA survival were explained by EMS and first responder measures was evaluated with additional adjustment for these factors. Results: Among 764 EMS agencies representing 258 342 OHCAs, 82 EMS agencies (10.7%) had a Black and Hispanic catchment area. Overall median age of the patients was 63.0 (IQR, 52.0-75.0) years, 36.1% were women, and 63.9% were men. Overall, the mean (SD) RSSR was 27.5% (3.6%), with lower survival at EMS agencies with Black and Hispanic catchment areas (25.8% [3.6%]) compared with agencies with White catchment areas (27.7% [3.5%]; P < .001). Among the 82 EMS agencies with Black and Hispanic catchment areas, a disproportionately higher number (32 [39.0%]) was in the lowest survival quartile, whereas a lower number (12 [14.6%]) was in the highest survival quartile. Additional adjustment for EMS response times, EMS termination of resuscitation rates, and first responder rates of initiating cardiopulmonary resuscitation or applying an automated external defibrillator before EMS arrival did not meaningfully attenuate differences in RSSRs between agencies with Black and Hispanic compared with White catchment areas (mean [SD] RSSRs after adjustment, 25.9% [3.3%] vs 27.7% [3.1%]; P < .001). Conclusions and Relevance: Risk-standardized survival rates for OHCA were 1.9% lower at EMS agencies working in Black and Hispanic catchment areas than in White catchment areas. This difference was not explained by EMS response times, rates of EMS termination of resuscitation, or first responder rates of initiating cardiopulmonary resuscitation or applying an automated external defibrillator. These findings suggest there is a need for further assessment of these discrepancies.

ACC/AHA Hypertension Guidelines and CHA2DS2-VASc Up-Scoring in Patients With Atrial Fibrillation.

This cohort study compares rates of hypertension among nonhypertensive patients with atrial fibrillation using JNC 8 vs ACC/AHA thresholds.

Baseline Health Status and its Association With Subsequent Cardiovascular Events in Patients With Atrial Fibrillation.

BACKGROUND: Clinical practice guidelines recommend optimizing the health status of patients with atrial fibrillation (AF) as a primary treatment goal. Whether disease-specific health status is associated with subsequent clinical events is unknown. OBJECTIVES: The aim of this study was to investigate the association between health status and subsequent clinical events among patients with AF. METHODS: Using a prospective cohort study of patients with new-onset AF referred to 11 hospitals (n = 3,313, 68.4% men, mean age 67.8 ± 11.6 years), data were extracted from 3,296 patients (99.4%) who completed the disease-specific Atrial Fibrillation Effects on Quality-of-Life (AFEQT) questionnaire between 2012 and 2018. Factors associated with baseline AFEQT overall summary (OS) score and associations between major adverse cardiovascular or neurologic events (MACNE; a composite of all-cause death, stroke, or new-onset heart failure hospitalization) over 2 years were investigated. RESULTS: Overall, 517 participants (15.6%) had poor to fair health status (AFEQT OS <60), and 1,035 (31.2%) had fair to good health status (AFEQT OS 60 to <80) at baseline. Female sex, younger age, family history of AF, higher baseline heart rate, paroxysmal AF, initial visit to the emergency department, and history of heart failure were associated with lower AFEQT OS scores. Of those, 226 participants (6.8%) experienced MACNE; restricted cubic spline analysis with adjustment for factors associated with baseline AFEQT score showed a nonlinear increase in the risk for MACNE with AFEQT OS score <80. The strongest associations were observed for baseline AFEQT daily activity scores (for AFEQT daily activity score of <80 vs ≥80, HR: 1.65; 95% CI: 1.21-2.25). CONCLUSIONS: Diminished health status in patients with AF is common and is independently associated with subsequent adverse cardiovascular events.

Complete Revascularization and Angina-Related Health Status in the ISCHEMIA Trial.

BACKGROUND: The impact of complete revascularization (CR) on angina-related health status (symptoms, function, quality of life) in chronic coronary disease (CCD) has not been well studied. OBJECTIVES: Among patients with CCD randomized to invasive (INV) vs conservative (CON) management in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), we compared the following: 1) the impact of anatomic and functional CR on health status compared with incomplete revascularization (ICR); and 2) the predicted impact of achieving CR in all INV patients compared with CON. METHODS: Multivariable regression adjusting for patient characteristics was used to compare 12-month health status after independent core laboratory-defined CR vs ICR in INV patients who underwent revascularization. Propensity-weighted modeling was then performed to estimate the treatment effect had CR or ICR been achieved in all INV patients, compared with CON. RESULTS: Anatomic and functional CR were achieved in 43.3% and 57.8% of 1,641 INV patients, respectively. Among revascularized patients, CR was associated with improved Seattle Angina Questionnaire Angina Frequency compared with ICR after adjustment for baseline differences. After modeling CR and ICR in all INV patients, patients with CR and ICR each had greater improvements in health status than CON, with better health status with CR than ICR. The projected benefits of CR were most pronounced in patients with baseline daily/weekly angina and not seen in those with no angina. CONCLUSIONS: Among patients with CCD in ISCHEMIA, health status improved more with CR compared with ICR or CON, particularly in those with frequent angina. Anatomic and functional CR provided comparable improvements in quality of life. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Health status and clinical outcomes in older adults with chronic coronary disease: the ISCHEMIA trial

BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29). CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Health Status and Clinical Outcomes in Older Adults With Chronic Coronary Disease: The ISCHEMIA Trial.

BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29). CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Derivation and validation of a predictive model for chronic stress in patients with cardiovascular disease.

BACKGROUND: Chronic stress in patients with cardiovascular disease (CVD), including peripheral artery disease (PAD), is independently associated worse outcomes. A model that can reliably identify factors associated with risk of chronic stress in patients with CVD is needed. METHODS: In a prospective myocardial infarction (MI) registry (TRIUMPH), we constructed a logistic regression model using 27 patient demographic, socioeconomic, and clinical factors, adjusting for site, to identify predictors of chronic stress over 1 year. Stress at baseline and at 1-, 6- and 12-month follow-up was measured using the 4-item Perceived Stress Scale (PSS-4) [range 0-16, scores ≥6 depicting high stress]. Chronic stress was defined as at least 2 follow-up PSS-4 scores ≥6. We identified and validated this final model in another prospective registry of patients with symptomatic PAD, the PORTRAIT study. RESULTS: Our derivation cohort consisted of 4,340 patients with MI (mean age 59.1 ± 12.3 years, 33% females, 30% non-white), of whom 30% had chronic stress at follow-up. Of the 27 factors examined, female sex, current smoking, socioeconomic status, and economic burden due to medical care were positively associated with chronic stress, and ENRICHD Social Support Instrument (ESSI) score and age were inversely related to chronic stress. In the validation cohort of 797 PAD patients (mean age 68.6±9.7 years, 42% females, 28% non-white, 18% chronic stress) the c-statistic for the model was 0.77 and calibration was excellent. CONCLUSIONS: We can reliably identify factors that are independently associated with risk of chronic stress in patients with CVD. As chronic stress is associated with worse outcomes in this population, our work identifies potential targets for interventions to as well as the patients that could benefit from these.

Association of Rapid Response Teams With Hospital Mortality in Medicare Patients.

BACKGROUND: Although rapid response teams have been widely promoted as a strategy to reduce unexpected hospital deaths, most studies of rapid response teams have not adjusted for secular trends in mortality before their implementation. We examined whether implementation of a rapid response team was associated with a reduction in hospital mortality after accounting for preimplementation mortality trends. METHODS: Among 56 hospitals in Get With The Guidelines-Resuscitation linked to Medicare, we calculated the annual rates of case mix-adjusted mortality for each hospital during 2000 to 2014. We constructed a hierarchical log-binomial regression model of mortality over time (calendar-year), incorporating terms to capture the effect of rapid response teams, to determine whether implementation of rapid response teams was associated with reduction in hospital mortality that was larger than expected based on preimplementation trends, while adjusting for hospital case mix index. RESULTS: The median annual number of Medicare admissions was 5214 (range, 408-18 398). The median duration of preimplementation and postimplementation period was 7.6 years (≈2.5 million admissions) and 7.2 years (≈2.6 million admissions), respectively. Hospital mortality was decreasing by 2.7% annually during the preimplementation period. Implementation of rapid response teams was not associated with a change in mortality during the initial year (relative risk for model intercept, 0.98 [95% CI, 0.94-1.02]; P=0.30) or in the mortality trend (relative risk for model slope, 1.01 per year [95% CI, 0.99-1.02]; P=0.30). Among individual hospitals, implementation of a rapid response team was associated with a lower-than-expected mortality at only 4 (7.1%) and higher-than-expected mortality at 2 (3.7%) hospitals. CONCLUSIONS: Among a large and diverse sample of US hospitals, we did not find implementation of rapid response teams to be associated with reduction in hospital mortality. Studies are needed to understand best practices for rapid response team implementation, to ensure that hospital investment in these teams improves patient outcomes.

Association of ambient air pollution with risk of out of hospital cardiac arrest in the United States.

Objective: We assessed the association of acute exposure to ambient air particulate matter < 2.5 µm (PM2.5) and Ozone with risk of out of hospital cardiac arrest (OHCA). Methods: We used data from the Cardiac Arrest Registry to Enhance Survival (CARES), a prospective multicenter registry of patients with OHCA in the U.S. Environmental data was obtained from publicly available data and linked with each patient. A case-crossover design was used to estimate association of acute exposure to ambient air PM2.5 and Ozone with risk of OHCA. Case day was defined as the day of the OHCA, and control days were same days of the week from preceding two weeks. Results: Of 187,047 patients with OHCA, mean age was 61.5 ± 19.9 years, 59.7 % were males and 47.1 % were of White race. Mean daily PM2.5 concentration on case day was 9.2 ± 4.9 µg/m3 and mean averaged 8-hour Ozone concentration was 36.9 ± 12.1 ppb. Each 5 µg/m3 increase in PM2.5 concentration (case day vs. control day) was not associated with risk of OHCA (OR 0.99 [95 % CI 0.998, 1.017] p = 0.72). In contrast, there was an association of exposure to Ozone with risk of OHCA with every 12 ppb increase in Ozone associated with a higher risk for OHCA on case day (OR 1.011 [95 % CI 1.003, 1.019] p = 0.01). Conclusion: In the U.S., higher exposure to Ozone was associated with increased risk of OHCA.

Association of Medication Adherence With Health Outcomes in the ISCHEMIA Trial.

BACKGROUND: The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes. OBJECTIVES: The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management. METHODS: Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive). RESULTS: Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment. CONCLUSIONS: More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).