Aim The "2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement)" describes a systematic approach for consistent implementation of "economic value statements" across ACC/AHA guidelines. It updates the cost-effectiveness threshold and proposes a new level of certainty framework that summarizes the strength of the available evidence. Additionally, it describes how cost-effectiveness analyses (CEAs) can help advance equity in population cardiovascular health. Methods A focused literature search was conducted from January 9, 2024, to February 2, 2024, encompassing English-language publications related to CEA methodology in PubMed, EMBASE, and the Cochrane Library, with publication dates ranging from 1973 to the present. Additional relevant studies published during the writing process (through June 25, 2024) were also considered by the writing committee. Structure This Cost/Value Methodology Statement updates prior guidance regarding the incorporation of evidence from published CEAs into clinical guidelines. It provides guidance for identifying and synthesizing relevant high-quality evidence, developing economic value statements, and communicating level of certainty in such statements. It defines the US cost-effectiveness threshold as $120,000 per quality-adjusted life year gained, highlights special considerations related to cardiovascular drugs and devices, emphasizes health equity considerations when interpreting CEAs, and defines a reference case for future CEAs.

BACKGROUND:The Get With The Guidelines-Heart Failure program is a national quality improvement initiative that was established in 2005 with the goal of improving the quality of care for patients hospitalized with heart failure. METHODS:We examined patient characteristics, adherence to achievement and quality measures, and in-hospital outcomes in patients hospitalized with heart failure among Get With The Guidelines-Heart Failure fully participating hospitals between 2005 and 2024. Measures were applied to eligible patients without documented contraindications. Multivariable regression analysis, adjusting for patient and hospital characteristics, was performed to assess temporal changes in individual measures and outcomes. RESULTS:Over the first 20 years, the Get With The Guidelines-Heart Failure program has grown to include 1 561 093 patient records (median age 73 [62-83], 47.4% women, median ejection fraction 45% [28%-58%]) and 819 participating hospitals. There was significant and sustained improvement in an all-or-none composite achievement metric, with an increase from 76.1% to 88.7% between 2005 and 2024 (adjusted odds ratio, 3.7 [95% CI, 3.5-4.0]; P<0.001). Rates of mineralocorticoid receptor antagonist prescriptions among eligible patients also increased substantially from 27.4% to 80.9% (adjusted odds ratio, 22.3 [95% CI, 20.2-24.6]; P<0.001). Meanwhile, prescriptions of new therapies such as angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors reached rates of 67.3% and 78.2% in 2024, respectively. Sustained improvements were also seen for other achievement and quality measures, including postdischarge follow-up and prescription of anticoagulation for patients with atrial fibrillation or atrial flutter. Equity of care by social vulnerability index also improved over time for guideline-based therapies such as evidence-based β-blockers and mineralocorticoid receptor antagonists. In contrast, vaccination rates and use of implantable cardioverter defibrillators saw recent decreases. CONCLUSIONS:The Get With The Guidelines-Heart Failure program was associated with sustained improvements in key achievement and quality measures for patients hospitalized with heart failure during its initial 2 decades, with a notable rise in the prescription of guideline-directed medical therapies and rapid implementation of new medications.

AIMS:In patients with heart failure with reduced ejection fraction (HFrEF), target-dose (vs. below-target-dose) angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improve clinical outcomes but worsen kidney function. Less is known about their effect on kidney failure (KF), especially in those with advanced chronic kidney disease (CKD), the examination of which was the objective of our study. METHODS AND RESULTS:Of the 154,945 Veterans with HFrEF (EF≤40%) and no baseline KF, 134,046 were initiated on ACEIs (target-dose, n=37,667) and 20,899 were initiated on ARBs (target-dose, n=4017) during 2000-2018. While remaining blinded to study outcomes, we assembled two propensity score-matched cohorts: ACEI (N=70,860; target-dose, n=35,430) and ARB (N=7900; target-dose, n=3950), balanced on 76 baseline characteristics. Hazard ratios (95% CIs) associated with target doses were estimated for 5-year KF and all-cause mortality, up to December 31, 2023. In the ACEI cohort, target-dose was associated with a 18% lower risk of KF (HR, 0.82; 95% CI, 0.75-0.89) and a 6% lower risk of death (HR, 0.94; 95% CI, 0.92-0.97). Subgroup and spline analyses showed that while the KF association was significant for those with baseline eGFR <35 ml/min/1.73m2, the mortality association was significant for those with eGFR ≥35 ml/min/1.73m2. In the ARB cohort, target-dose had no association with outcomes. CONCLUSIONS:In patients with HFrEF, target-dose (vs. below-target-dose) ACEIs, but not ARBs, were associated with lower risk of KF, which was significant in those with advanced CKD. The survival benefit was modest and limited to those without advanced CKD.

BACKGROUND:Major heart failure (HF) registries are limited by manual chart abstraction and are limited to hospitalized patients. Using artificial intelligence (AI) approaches and electronic health record (EHR) data from the Veterans Affairs (VA) health care system, we have assembled the National District of Columbia (DC) VA-HF Registry, which includes both ambulatory and hospitalized patients with HF. In the current study, we descriptively compared these patients with those identified using International Classification of Diseases (ICD) codes. METHODS:We identified 1,416,512 veterans with at least 1 ICD code for HF in the VA national EHR between 1999 and 2017. The first date of an ICD code for HF was considered the index HF date. We used validated encounter-based AI approaches based on machine learning and natural language processing models, and ICD code-based approaches on the basis of ≥1 hospitalization or ≥2 outpatient encounters due to HF, to assemble the AI-HF and ICD-HF cohorts, respectively. The 2 cohorts were compared by using absolute standardized differences, with values ≥10% indicating clinical significance. All analyses were descriptive, and no inferential or causal claims were made. RESULTS:The AI and ICD approaches assembled 1,031,970 and 614,828 patients, respectively, after a mean of 0.4 and 1.0 years from the index HF date. Patients in the AI-HF (vs the ICD-HF) cohort had a mean age of 71.4 (vs 70.5) years, 98.1% (vs 98.0%) were men, 13.9% (vs 16.1%) were African American, and 7.7% (vs 13.4%) had index HF hospitalizations, with absolute standardized differences of 8%, 1%, 6%, and 18%, respectively, which were <10% for 66 other baseline characteristics. The 1-year post-index HF hospitalizations occurred in 10.7% and 15.6% of patients in the AI-HF and ICD-HF cohorts, respectively. The 1‑year mortality rate was lower in the ICD-HF cohort, reflecting expected immortal‑time bias due to later cohort qualification. CONCLUSIONS:The findings of this descriptive study demonstrate that the AI approach assembled a substantially larger cohort that included most patients identified by using the ICD code approach, suggesting broad consistency between the 2 approaches. Future external validation is needed to determine its potential use as a robust tool for improving patient care, health-services operations, and clinical research in HF.

AIMS:Target-dose angiotensin-converting enzyme inhibitors (ACEIs), compared with below-target doses, have been associated with lower risks of death and kidney failure (KF) in patients with heart failure with reduced ejection fraction (HFrEF). We examined these associations in heart failure with preserved ejection fraction (HFpEF). METHODS:Among 96,473 Veterans with HFpEF (EF ≥ 50%) newly initiated on ACEIs (2000-2018), 32,728 received target doses recommended for HFrEF. Propensity scores for receiving target-dose ACEIs were used to assemble an outcome-blinded matched cohort of 61,160 patients (target-dose, n=30,580), balanced on 76 baseline characteristics. Outcomes were 5-year all-cause mortality, incident KF, and HF hospitalization. RESULTS:Compared with below-target-dose ACEIs, target-dose ACEIs were associated with a lower KF risk (HR, 0.89; 95% CI, 0.83-0.97), no mortality difference (HR, 0.99; 95% CI, 0.97-1.02), and a higher risk of HF hospitalization (HR, 1.08; 95% CI, 1.04-1.12). Among 16,735 patients with chronic kidney disease (CKD; eGFR 15-59 mL/min/1.73 m2), target-dose ACEIs were associated with a lower risk of KF (HR, 0.82; 95% CI, 0.75-0.90) and mortality (HR, 0.93; 95% CI, 0.89-0.96) without a higher HF hospitalization risk (HR, 0.95; 95% CI, 0.90-1.01). Each association differed significantly from those in patients with eGFR ≥ 60 mL/min/1.73 m2 (interaction p<0.001). CONCLUSION:In HFpEF, target-dose ACEIs were associated with a lower risk of KF, a higher risk of HF hospitalization, and no association with mortality. These associations were consistently more favorable in the subgroup with CKD. These findings underscore the importance of evaluating treatment strategies within biologically coherent HFpEF phenotypes.

BACKGROUND:The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire is endorsed for symptom and quality-of-life assessment in atrial fibrillation (AF) but is typically measured once. Because patient-reported health status changes with treatment, serial AFEQT assessments may better reflect disease burden over time. We evaluated whether repeated AFEQT measurements are associated with subsequent outcomes and whether the most recent score is informative. METHODS AND RESULTS:We analyzed a multicenter, prospective registry of stable outpatients with AF referred to 11 hospitals in Japan (2012-2018). Associations of baseline ("prior"), 12-month ("current"), and change in AFEQT overall summary (os) scores with all-cause death and heart failure (HF) hospitalization were examined using multivariable Cox models. Among 2,743 patients (mean [±SD] age 67.8±11.1 years; 31.9% women), 146 (5.3%) experienced HF hospitalization and 134 (4.9%) died over a median follow-up of 4.0 years. Higher current AFEQT-os and change scores, but not prior AFEQT-os, were associated with a lower risk of death/HF hospitalization, with adjusted hazard ratios (95% confidence intervals) per 5-point increase of 0.94 (0.91-0.97) and 0.96 (0.92-0.99), respectively. When modeled together, only current AFEQT-os remained independently associated with outcomes. In time-varying analyses, time-updated AFEQT-os predicted both death/HF hospitalization and all-cause death. CONCLUSIONS:The most recent AFEQT-os is associated with mortality and HF hospitalization, whereas baseline scores provide limited prognostic value. Updating patient-reported health status may help with risk assessment in AF.

Aims In randomized controlled trials, target-dose angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF), although the mortality reduction was not statistically significant. Target doses worsened kidney function, but kidney failure (KF) was not evaluated. We compared KF and mortality between below-target-dose and target-dose ACEIs and ARBs in patients with HFrEF, overall and stratified by advanced chronic kidney disease (CKD) status. Methods Of the 154 945 Veterans with HFrEF (left ventricular ejection fraction <= 40%) and no baseline KF, 134 046 were initiated on ACEIs (target-dose, n = 37 667), and 20 899 were initiated on ARBs (target-dose, n = 4017) during 2000-18. While remaining blinded to study outcomes, we assembled two propensity score-matched cohorts: ACEI (N = 70 860; target-dose, n = 35 430) and ARB (N = 7900; target-dose, n = 3950), balanced on 76 baseline characteristics. Hazard ratios [95% confidence intervals (CIs)] associated with target doses were estimated for 5-year KF and 5-year all-cause mortality, through 31 December 2023. Results In the ACEI cohort, target-dose was associated with an 18% (95% CI, 11%-25%) lower risk of KF and a 6% (95% CI, 3%-8%) lower risk of death. Subgroup and spline analyses showed that the KF association was significant among those with baseline estimated glomerular filtration rate < 35 mL/min/1.73 m(2), whereas the mortality association was significant among those with estimated glomerular filtration rate >= 35 mL/min/1.73 m(2). Target-dose ACEIs were associated with a 3% (95% CI, 1%-6%) higher risk of heart failure hospitalization and a 7% (95% CI, 0%-14%) higher risk of hospitalization due to acute kidney injury. In the ARB cohort, target-dose had no association with outcomes. Conclusion Among patients with HFrEF, target-dose (vs below-target-dose) ACEIs, but not ARBs, were associated with a lower risk of KF (despite a higher risk of AKI), which was limited to those with advanced chronic kidney disease. The survival benefit was modest and limited to those without advanced chronic kidney disease.

BACKGROUND:In patients with relatively stable heart failure with reduced ejection fraction (HFrEF), target-dose angiotensin-converting enzyme inhibitors (ACEIs), compared with below-target doses, reduce the risks of death and kidney failure (KF). Whether these benefits extend to hospitalized patients, who are less likely to receive target doses due to hemodynamic instability and impaired kidney function, remains uncertain. METHODS:Of the 15,152 Veterans with HFrEF (LVEF ≤40%) without baseline KF, who were hospitalized for acute decompensated HF between 2000-2018 and newly initiated on ACEIs prior to discharge, 3143 (20.7%) received guideline‑recommended target doses. Propensity scores for the receipt of target-dose were calculated for each of the 15,152 patients and used to match 2884 (91.8% of 3143) target-dose patients to 2884 below-target-dose patients. Hazard ratios (HRs) for mortality and KF associated with target-dose ACEIs were estimated. RESULTS:Matched patients (n=5768) had mean (±SD) age 66 (±12) years, LVEF 26% (±9%), eGFR 76 (±23) mL/min/1.73 m², 99% were men, and 36% were African American. Patients in the two dose groups were balanced on 76 baseline characteristics. During 5 years of follow‑up, all‑cause mortality occurred in 56.1% of below‑target‑dose patients and 52.6% of target‑dose patients. KF occurred in 4.2% and 3.6%, respectively. Target‑dose ACEIs were associated with a 9% lower risk of death (HR 0.91; 95% CI, 0.85-0.98). The HR for KF was 0.83 (95% CI, 0.64-1.08), and for the composite endpoint of KF or death was 0.90 (95% CI, 0.84-0.97). CONCLUSION:The observed renal safety and lower mortality in patients with HFrEF newly initiated on ACEIs at higher target doses before discharge support the use of this inpatient strategy and suggest it may help mitigate the persistent outpatient inertia in the initiation and up‑titration of evidence‑based HF therapies.

BACKGROUND:Magnesium is essential for myocardial function and rhythm. Although typically well-regulated, patients with heart failure are prone to magnesium deficiency. Most clinical laboratories define normal serum magnesium as 1.6-2.6 mg/dL, but this range may include chronic latent magnesium deficiency. The Magnesium Global Network (MaGNet) recommends 2.1-2.3 as optimal. We examined outcomes in heart failure patients across and outside these ranges. METHODS:Using ambulatory serum magnesium levels, we categorized 627,349 Veterans with heart failure (2001-2023) into <1.6 (6%), 1.6-1.7 (11%), 1.8-2.0 (39%), 2.1-2.3 (34%; reference) and >2.3 (10%) mg/dL. Cox models estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year mortality. Restricted cubic spline models assessed nonlinear associations between serum magnesium as a continuous variable, using two reference values: the lower limits of the current clinical reference range (1.6-2.6 mg/dL) and the MaGNet range (2.1-2.3 mg/dL). RESULTS:All-cause mortality occurred in 15.4%, 13.3%, 11.6%, 11.5%, and 16.2% of the patients with serum magnesium <1.6, 1.6-1.7, 1.8-2.0, 2.1-2.3, and >2.3 respectively. Corresponding adjusted HRs (95% CIs) were 1.36 (1.32-1.41), 1.23 (1.20-1.26), 1.07 (1.05-1.09), 1.00 (reference), and 1.23 (1.20-1.26), respectively. When the lower limit of current clinical reference range (1.6-2.6 mg/dL) was used as the reference, restricted cubic spline analysis revealed a U-shaped association, with the lowest HR between 1.6 and 2.6 mg/dL, with significantly higher risks outside these ranges. CONCLUSIONS:In US Veterans with heart failure, ambulatory serum magnesium levels showed an independent U-shaped association with one-year mortality, with the lowest risk observed between 1.6 and 2.6 mg/dL, consistent with the current clinical reference range, and higher risks at both lower and higher levels.

Background:Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) reduces mortality rates but remains widely underused. A polypill for HFrEF has been proposed as an implementation strategy to improve GDMT delivery, but little is known about physicians' preferences in the design of HFrEF polypills. Discrete choice experiments (DCEs), in which survey respondents choose among hypothetical products, are a powerful tool in health economics research and can lend insight into key tradeoffs in HFrEF polypill design. However, the process of designing DCEs is complex and often poorly reported. Methods:We developed a survey instrument, including a DCE, through a 5-stage mixed-methods process including (1) literature review; (2) physician interviews and surveys; (3) attribute generation; (4) expert review; and (5) pilot testing. We applied a D-efficient design approach using a multinomial logic model to determine the number of choice tasks for the DCE. Results:We designed a DCE with 4 attributes: HFrEF polypill out-of-pocket cost, inclusion of an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or sacubitril/valsartan, ancillary support for polypill prescribing, and pharmacy availability. The final survey will be distributed to cardiologists in academic and Veterans Administration medical centers across the United States. Conclusions:Through a rigorous multistage design process leveraging mixed methods, we developed a DCE that elicits cardiologists' preferences about HFrEF polypills and key tradeoffs in their design. Results from this DCE study will directly inform future HFrEF polypill cluster-randomized clinical trials.