Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. OBJECTIVES: The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. METHODS: CHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. RESULTS: The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment. CONCLUSIONS: Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial.

BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Association of Social Support and Health Status Outcomes in Peripheral Artery Disease.

OBJECTIVE: A critical goal in the care of patients with peripheral artery disease (PAD) is to optimize their health status; their symptoms, function, and quality of life. Social support has been proposed to be a predictor of disease-specific health status in PAD. However, the prevalence of low perceived social support, the association with health status outcomes, and the interaction with other biopsychosocial variables, is unknown. Our aim was to assess the association of baseline perceived social support with health status at 12 months in patients with PAD. METHODS: The PORTRAIT registry, which enrolled patients with PAD in the United States, Netherlands, and Australia from 2011-2015, was used. Perceived social support was assessed at baseline with the ENRICHD Social Support Inventory (ESSI), while disease-specific (Peripheral Artery Disease Questionnaire [PAQ]) and generic health status (EuroQoL Visual Analog Scale (VAS) and EQ-5D-3L Index) questionnaires were assessed at baseline and 12 months. Low social support was defined as a score ≤ 3 on 2 items and an ESSI score ≤ 18. A hierarchical mixed level linear regression model adjusting for biopsychosocial variables was used to assess the association between low perceived social support and the ESSI score with health status at 12 months. RESULTS: A total of 949 patients were included (mean age 67.64±9.32 years, 37.9% females), with low social support being present in 18.2%. Patients with low social support were more likely to not be married or to be living alone (50.0% vs 77.5%; p<0.001), have more financial constraints, have more depressive, stress, and anxiety symptoms, and have lower disease-specific and generic health status at baseline and at 12 months. In the unadjusted model, low social support was associated with a -7.02 (95%CI -10.97; -3.07) point reduction in the PAQ, -7.43 (95%CI -10.33; -4.54) in the VAS, and -0.06 (95%CI -0.09; -0.03) in the EQ-5D-3L Index. Adjusting for biopsychosocial factors minimally attenuated these associations (PAQ: -6.52 95%CI -10.55; -2.49 p=0.002 , VAS: -5.39 95%CI 8.36; -2.42 p <0.001 , EQ-5D-3L Index -0.04 95%CI -0.07; 0.01 p=0.022). The ESSI per-point score was associated with a decrease of 0.51 (95%CI 0.18; 0.85; p=0.003) in PAQ and 0.46 (95%CI 0.12; 0.61; p=0.004) in the VAS. CONCLUSION: Among patients with PAD, low social support was frequent and associated with lower health status at 1 year independently of other biopsychosocial variables. Improving social support could improve health status and outcomes in PAD.

Use of Calcium Modification During Percutaneous Coronary Intervention After Introduction of Coronary Intravascular Lithotripsy.

Background: Calcified coronary lesions are a challenge for percutaneous coronary interventions (PCIs). Coronary intravascular lithotripsy (IVL) is a novel calcium modification technology approved for commercial use in February 2021, but little is known about its uptake in US clinical practice. Methods: We described trends in use of calcium modification strategies, variation in use across hospitals, and predictors of calcium modification and IVL use in PCI. We included National Cardiovascular Data Registry CathPCI Registry patients who underwent PCI between April 1, 2018, and December 31, 2022. We examined trends and hospital variation in calcium modification and IVL use. We used multivariate hierarchical logistic regression to identify predictors of calcium modification and IVL use at hospitals in 2022. Results: Of 2,733,494 PCIs across 1676 hospitals over 4.75 years, 11.4% were performed with calcium modification. Coronary IVL use increased rapidly from 0% of PCIs in Q4 2020 to 7.8% of PCIs in Q4 2022, which was accompanied by an overall increase in use of all calcium modification strategies (11.1%-16.0%) during this period with a slight corresponding decrease in coronary atherectomy use (5.4%-4.4%). In 2022, there was wide variation in IVL use across hospitals (median, 3.86%; IQR, 0%-8.19%), with IVL being the most common calcium modification strategy in 48% of hospitals. The treating hospital was the strongest predictor of calcium modification (median odds ratio [OR], 2.49; 95% CI, 2.40-2.57) and IVL use (median OR, 2.89; 95% CI, 2.74-3.04). Conclusions: IVL has rapidly changed the landscape of calcium modification use for PCI, although there remains wide variation across hospitals.

Burden of Heart Failure in Patients With Tricuspid Regurgitation and Effect of Transcatheter Repair on Different Subdimensions of Quality of Life.

BACKGROUND: Right-sided heart failure (HF) due to severe tricuspid regurgitation (TR) is associated with reduced quality of life (QoL). Here, we analyzed the impact of TR on specific QoL dimensions and the effect of transcatheter tricuspid valve intervention (TTVI) on individual QoL items. METHODS AND RESULTS: In this study, we included 174 patients with HF (49% women; median age, 79 years; 97% New York Heart Association ≥3) with baseline QoL assessment undergoing TTVI by transcatheter edge-to-edge-repair at our center between April 2016 and March 2022. QoL was assessed by the standardized Minnesota Living With HF Questionnaire. QoL change after TTVI and correlation to functional end points were analyzed. In addition, all QoL domains and the 21 individual items of the Minnesota Living With HF Questionnaire were analyzed. TTVI significantly reduced TR (TR ≥3: baseline 95%, 1-year-follow-up 7%; P<0.001). Total Minnesota Living with HF Questionnaire score improved from 37 (interquartile range, 26-50) points to 31 (interquartile range, 17-42) points (median follow-up-interval, 355 days; P<0.001). QoL improvement was associated with positive New York Heart Association class, 6-minute walking distance, and actigraphy changes (all P<0.05). The detailed analysis revealed that all items of the physical-related QoL dimension were impaired at baseline and strongly improved after TTVI. In contrast, the emotional and "social" Minnesota Living With HF Questionnaire dimensions were largely unaffected at baseline, yet specific items improved with TTVI. CONCLUSIONS: In this single-center study, we delineate the QoL-associated disease burden of TR and identify specific QoL items that improved after TTVI. Our findings support TTVI in patients with reduced QoL and may add to the development of specific tools assessing the functional status of an increasing patient population undergoing TTVI.

Association of Medication Adherence and Health Status in Heart Failure With Reduced Ejection Fraction: Insights From the CHAMP-HF Registry.

BACKGROUND: The foundation for managing heart failure with reduced ejection fraction (HFrEF) is adherence to guideline-directed medical therapy. Finding an association between medication adherence and patients' health status (their symptoms, function, and quality of life) can be used to underscore its importance to patients. METHODS: The association of self-reported medication adherence in US outpatients with HFrEF enrolled in the Change the Management of Patients with Heart Failure registry from 2015 to 2017 was compared with their health status at baseline and 12 months later. A secondary analysis of changes in adherence between baseline and 6 months with 6-month health status was also performed. Medication adherence was assessed with the self-reported 4-item Morisky-Green-Levine Medication Adherence Scale, with scores ≥1 classified as nonadherent. The primary health status outcome was the disease-specific 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS; range, 0-100; higher is better). Robust linear regression models adjusted for confounders were used. RESULTS: After excluding those who died (n=316) or did not provide 12-month KCCQ (n=1285), 3495 outpatients with HFrEF were included, of whom 1108 (31.7%) reported being nonadherent. Nonadherent participants were younger, had significantly worse baseline health status (-5.83-point difference; P<0.001), and showed less improvement at 12 months (-1.7-point difference in mean change; P=0.017) than adherent participants. Among nonadherent patients at baseline, those whose adherence improved trended toward greater 6-month health status improvements than those remaining nonadherent (fully adjusted difference of 2.52 points; P=0.054). CONCLUSIONS: In HFrEF, medication nonadherence was associated with worse health status and less improvement over the following year. Improvements in adherence were associated with better health status than remaining nonadherent, underscoring the importance of supporting adherence with guideline-directed medical therapy in patients with HFrEF.

Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

BACKGROUND: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). METHODS AND RESULTS: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5-20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site-interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8-24), and washout (weeks 24-28), and included major adverse cardiac events, new-onset atrial fibrillation, implantable cardioverter-defibrillator discharges, LVEF <50%, and treatment-emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5-, 10-, 15-, and 20-mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by -0.9% (95% CI, -1.3 to -0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per-protocol dose reduction for site-interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment-emergent adverse events were similar between treatment groups, including atrial fibrillation. CONCLUSIONS: A site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05186818.

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.

A comparison of quality-adjusted life years in older adults after heart transplantation versus long-term mechanical support: Findings from the SUSTAIN-IT study.

BACKGROUND: The quality-adjusted life year (QALY) measures disease burden and treatment, combining overall survival and health-related quality of life (HRQOL). We estimated QALYs in 3 groups of older patients (60-80 years) with heart failure (HF) who underwent heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS] or HT without pre-transplant MCS [HT Non-MCS]) or long-term MCS (destination therapy). We also identified factors associated with gains in QALYs through 24 months follow-up. METHODS: Of 393 eligible patients enrolled (10/1/15-12/31/18) at 13 U.S. sites, 161 underwent HT (n = 68 HT MCS, n = 93 HT Non-MCS) and 144 underwent long-term MCS. Survival and HRQOL data were collected through 24 months. QALY health utilities were based on patient self-report of EQ-5D-3L dimensions. Mean-restricted QALYs were compared among groups using generalized linear models. RESULTS: For the entire cohort, mean age in years closest to surgery was 67 (standard deviation, SD: 4.7), 78% were male, and 83% were White. By 18 months post-surgery, sustained significant differences in adjusted average ± SD QALYs emerged across groups, with the HT Non-MCS group having the highest average QALYs (24-month window: HT Non-MCS = 22.58 ± 1.1, HT MCS = 19.53 ± 1.33, Long-term MCS = 19.49 ± 1.3, p = 0.003). At 24 months post-operatively, a lower gain in QALYs was associated with HT MCS, long-term MCS, a lower pre-operative LVEF, NYHA class III or IV before surgery, and an ischemic or other etiology of HF. CONCLUSIONS: Determination of QALYs may provide important information for policy makers and clinicians to consider regarding benefits of HT and long-term MCS as treatment options for older patients with HF.

Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

Effect of PCI on Health Status in Ischemic Left Ventricular Dysfunction: Insights From REVIVED-BCIS2.

BACKGROUND: In the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial, percutaneous coronary intervention (PCI) did not reduce the incidence of death or hospitalization for heart failure (HHF). OBJECTIVES: This prespecified secondary analysis investigated the effect of PCI on health status measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) combined with the primary outcome in a win ratio. METHODS: Participants with severe ischemic left ventricular dysfunction were randomized to either PCI in addition to optimal medical therapy (OMT) (PCI) or OMT alone (OMT). The primary outcome was a hierarchical composite of all-cause death, HHF, and KCCQ-Overall Summary Score (OSS) at 24 months analyzed using the unmatched win ratio. The key secondary endpoint was a KCCQ-OSS responder analysis. RESULTS: A total of 347 participants were randomized to PCI and 353 to OMT. Median age was 70.0 years (Q1-Q3: 63.3-76.1 years). Mean left ventricular ejection fraction was 27.0 ± 6.7%. PCI did not improve the primary endpoint (win ratio for PCI vs OMT: 1.05; 95% CI: 0.88-1.26; P = 0.58). PCI resulted in more KCCQ-OSS responders than OMT at 6 months (54.1% vs 40.7%; OR: 1.96; 95% CI: 1.41-2.71; P < 0.001) and fewer deteriorators (25.2% vs 31.4%; OR: 0.69; 95% CI: 0.47-1.00; P = 0.048). PCI did not impact KCCQ-OSS responders or deteriorators at 12 or 24 months. CONCLUSIONS: PCI did not improve the hierarchical composite of death, HHF, and health status at 2 years. PCI improved KCCQ-OSS at 6 months, but this benefit was not sustained to 1- or 2-year follow-up. (Revacularization for Ischemic Ventricular Dysfunction [REVIVED-BCIS2]; NCT01920048).

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.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Factors associated with coronary angiography performed within 6 months of randomization to the conservative strategy in the ISCHEMIA Trial

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14­2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78­12.86] and 2.63 [95% CI, 1.51­4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23­3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34­2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46­0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.

Clinical Impact of Routine Assessment of Patient-Reported Health Status in Heart Failure Clinic: The PRO-HF Trial.

BACKGROUND: The impact of routine clinic use of patient-reported outcome (PRO) measures on clinical outcomes in patients with heart failure (HF) has not been well-characterized. We tested if clinic-based use of a disease-specific PRO improves patient-reported quality of life at 1 year. METHODS: The PRO-HF trial (Patient-Reported Outcome Measurement in Heart Failure Clinic) was an open-label, parallel, patient-level randomized clinical trial of routine PRO assessment or usual care at an academic HF clinic between August 30, 2021, and June 30, 2022, with 1 year of follow-up. In the PRO assessment arm, participants completed the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at each HF clinic visit, and results were shared with their treating clinician. The usual care arm completed the KCCQ-12 at randomization and 1 year later, which was not shared with the treating clinician. The primary outcome was the KCCQ-12 overall summary score (OSS) between 12 and 15 months after randomization. Secondary outcomes included domains of the KCCQ-12, hospitalization and emergency department visit rates, HF medication therapy, clinic visit frequency, and testing rates. RESULTS: Across 17 clinicians, 1248 participants were enrolled and randomized to PRO assessment (n=624) or usual care (n=624). The median age was 63.9 years (interquartile range [IQR], 51.8-72.8), 38.9% were women, and the median baseline KCCQ-12 OSS was 82.3 (IQR, 58.3-94.8). Final KCCQ-12 (available in 87.9% of the PRO arm and 85.1% in usual care; P=0.16) median OSS were 87.5 (IQR, 68.8-96.9) in the PRO arm and 87.6 (IQR, 69.7-96.9) in the usual care arm with a baseline-adjusted mean difference of 0.2 ([95% CI, -1.7 to 2.0]; P=0.85). The results were consistent across prespecified subgroups. A post hoc analysis demonstrated a significant interaction with greater benefit among participants with a baseline KCCQ-12 OSS of 60 to 80 but not in less or more symptomatic participants. No significant differences were found in 1-year mortality, hospitalizations, emergency department visits, medication therapy, clinic follow-up, or testing rates between arms. CONCLUSIONS: Routine PRO assessment in HF clinic visits did not impact patient-reported quality of life or other clinical outcomes. Alternate strategies and settings for embedding PROs into routine clinical care should be tested. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04164004.

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).

One-month DAPT with ticagrelor and aspirin for patients undergoing coronary artery bypass grafting: rationale and design of the randomised, multicentre, double-blind, placebo-controlled ODIN trial.

The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).