International Journal of Cardiology

Introduction Percutaneous coronary intervention (PCI) is a widely adopted strategy for managing coronary artery disease (CAD), leading to improved survival rates, particularly in developing countries. However, the increased survival of these patients imposes a substantial burden on long-term management, especially at the primary healthcare level. Recently, the hemoglobin-to-red cell distribution width ratio (HRR) has emerged as a potentially valuable prognostic biomarker for post-PCI patients. Despite its accessibility and cost-effectiveness, HRR has not been extensively investigated in resource-limited settings. Aim This study aimed to evaluate the prognostic value of the HRR in predicting 3-year major adverse cardiovascular events (MACE) among patients undergoing PCI who were managed at the primary healthcare level. Methods We conducted a multicenter prospective cohort study in Vietnam. A total of 626 post-PCI patients were ultimately included in the final analysis. The study commenced in October 2019 and concluded in October 2025. The association between HRR and 3-year MACE was evaluated using Cox proportional hazards regression models. Results The MACE incidence decreased progressively across the ascending HRR quartiles (p < 0.001). According to the unadjusted Cox model, each unit increase in HRR was associated with a lower risk of MACE (HR = 0.756; 95% CI, 0.703-0.814; p < 0.001). This association persisted after adjustment for age, sex, comorbidities (Model I: HR = 0.810; 95%CI: 0.750-0.878; p < 0.001). HRR outperformed its individual components, hemoglobin and red cell distribution width. Subgroup analyses confirmed the consistency of the association across clinically relevant strata. Calibration and decision-curve analyses further suggested acceptable risk estimation and potential clinical utility of HRR for 3-year MACE risk stratification. In the discriminative analysis for predicting 3-year MACE, the HRR had the highest area under the curve outperforming other inflammation-based indices. Conclusion A lower HRR was independently associated with a greater 3-year MACE risk in post-PCI patients. HRR outperforms commonly used leukocyte- and platelet-derived indices, highlighting its potential utility as a simple, cost-effective prognostic marker in resource-constrained healthcare settings.

Abstract Background The SYNTAX score (SS) quantifies the severity and complexity of coronary artery lesions and serves as an independent predictor of major adverse cardiovascular events and mortality in patients with acute coronary syndrome (ACS). However, few studies have examined the association between SS and in-hospital cardiac arrest (IHCA) in this population. Therefore, this study aims to elucidate the relationship between SS and the incidence of IHCA in patients with ACS. Methods This study consecutively enrolled 3,224 patients undergoing percutaneous coronary intervention (PCI). Logistic regression and restricted cubic spline (RCS) analyses were employed to examine the association between SS and the incidence of IHCA. Participants were stratified into three groups based on SS: Group T1 (SS ? 10, N = 1,097), Group T2 (10 < SS ? 18, N = 1,089), and Group T3 (SS > 18, N = 1,038). The primary endpoint was the incidence of IHCA. Results The overall incidence of IHCA was 4% (N=147). After adjusting for covariates, SS was significantly associated with the incidence of IHCA in ACS patients treated with PCI (OR = 1.0400; 95% confidence interval (CI) = 1.0200?1.0700; p < 0.001). Compared with the T1 group, the T3 group exhibited an increased risk of IHCA (OR = 2.1800; 95% CI = 1.2900?3.6900; p = 0.0040). Subgroup analyses revealed that, after covariate adjustment, patients with ST-segment elevation myocardial infarction (STEMI) had an increased risk of IHCA (OR = 1.0700; 95% CI = 1.0300?1.1100; p < 0.001). Similarly, both patients with diabetes mellitus (DM) (OR = 1.0400; 95% CI = 1.000?1.0700; p = 0.0270) and those without DM (OR = 1.0600; 95% CI = 1.0200?1.1000; p = 0.0020) showed an increased risk. Furthermore, elderly patients (?60 years) (OR = 1.0300; 95% CI = 1.0100?1.0700; p = 0.0210) and non-elderly patients (<60 years) (OR = 1.0500; 95% CI = 1.000?1.1000; p = 0.0470) had an increased risk, as did male patients (OR = 1.0500; 95% CI = 1.0200?1.0700; p = 0.0020). RCS analysis indicated a dose-response relationship between IHCA incidence and SS (nonlinear p-value = 0.906), with the risk of IHCA increasing when SS exceeded 23.975. Incorporating SS into the baseline risk model improved the predictive value for IHCA incidence in ACS patients undergoing PCI (Net reclassification improvement [NRI]: 0.3537 [0.1906?0.5167], p < 0.001; Integrated discriminant improvement [IDI]: 0.0104 [0.0025?0.0183], p = 0.0097). Conclusions Among patients with ACS undergoing PCI, SS is significantly associated with the incidence of IHCA. Consequently, SS may serve as an effective predictor of IHCA in this population.

Background Studies of the 2018 United Network for Organ Sharing (UNOS) policy revision suggest improved early transplantation access for the sickest patients. It remains unknown whether these benefits vary as a function of time on the waitlist. Thus, we evaluated potential time-dependent effects of the 2018 heart allocation policy revision on waitlist outcomes. Methods Using UNOS data, we analyzed adult heart transplant candidates listed five years before (pre-policy) and after (post-policy) policy change, categorized as high-acuity (Status 1-3 or 1A) or low-acuity (Status 4-6 or 1B/old 2). Landmark analysis at weeks 0, 1, 2, 4, 8, 16, 24 using a competing risks framework was performed to assess transplantation, death/deterioration, and myocardial recovery. Sub-distribution and cause-specific hazard ratios were calculated. Absolute number and proportion of far-away transplants (donor distance [&ge;]500 nautical miles) were calculated at each timepoint. Results High-acuity patients experienced significantly higher risk of transplantation within 2 weeks post-policy change but equivocal risk by week 16. Low-acuity patients exhibited increased rate/risk of myocardial recovery and equal or improved death/deterioration risk at all timepoints; early transplantation cumulative incidence was increased. At all timepoints, both groups experienced significantly increased far-away donor use, highest immediately after listing and progressively declining over time. Conclusions The 2018 heart allocation policy change resulted in an initial appearance of time-dependent benefits among high-acuity, post-policy patients, but this was likely due to rapid transplantation of Status 1 and 2 patients from broader geographic sharing rather than a true temporal phenomenon. Post-policy, low-acuity patients experience benefits in all waitlist outcomes.

BACKGROUND The optimal antiplatelet regimen in patients with acute coronary syndrome (ACS) and multivessel disease undergoing drug-coated balloon (DCB) angioplasty remains unclear. METHODS This was a prespecified subgroup analysis of the REC-CAGEFREE II trial, which was conducted at 41 sites in China and randomized 1948 exclusively DCB-treated participants with ACS to stepwise dual antiplatelet therapy (DAPT) de-escalation or standard DAPT. The primary endpoint was net adverse clinical events (NACE; including all-cause death, stroke, myocardial infarction, revascularization, and BARC type 3 or 5 bleeding) at 12 months. Participants were stratified into multivessel and single-vessel subgroups according to angiographic characteristics. RESULTS Overall, 720/1948 (37.0%) patients had multivessel disease. The multivessel subgroup was associated with a significantly higher risk of NACE compared with the single-vessel subgroup (12.5% versus 6.7%, HR IPTW:1.84, 95%CI:1.35-2.51, P<0.001). No significant interaction was observed between vessel status (multivessel or single-vessel) and treatment allocation with respect to NACE (Pinteraction=0.542). In the multivessel subgroup, NACE occurred in 44/368 (12.1%) and 45/352 (12.9%) in the stepwise de-escalation and standard DAPT groups (HR IPTW:0.95, 95%CI:0.62-1.75, P=0.818), respectively. In the single-vessel subgroup, NACE occurred in 43/607 (7.1%) and 39/621 (6.3%) in the stepwise de-escalation and standard groups (HR IPTW:1.12, 95%CI:0.72-1.70, P=0.611), respectively. For the prespecified hierarchical secondary endpoint, win ratio analyses yielded more wins for stepwise de-escalation in both subgroups. CONCLUSIONS Among patients with ACS undergoing DCB-only angioplasty, those with multivessel disease were associated with a higher risk of NACE than those with single-vessel disease. Stepwise DAPT de-escalation and standard DAPT exhibited similar risk-benefit profiles in both subgroups.

BACKGROUND: Machine learning (ML) models have been used to evaluate one-year post-transplant mortality in donor-recipient pairs. Previous modeling utilizing noninterpretable ML methods (deep neural networks [DNN] and XGBoost) showed modest gains in area under the receiver operating curve (AUC) beyond logistic regression, but suffered a significant drop in predictive AUC applied to the subsequent years' data and lacked statistical significance in validating previously identified risk factors. METHODS: Using balanced SRTR datasets, we evaluated non-interpretable models against interpretable ML models (adaptive logistic regression with interaction terms [aLR], Classification and Regression tree [CART], and conditional inference tree [CIT]) for one-year mortality, including comprehensive clinician-supervised data curation and inclusion of variables describing pre- and post-2018 listing status changes. Models were trained/tested using rolling-window validation across years and further analyzed with repeated ten-fold crossvalidation. Interaction terms were obtained via Adaptive Best-Subset Selection (ABESS). RESULTS: Predictive validation before the listing policy change in 2018 showed similar AUCs between DNN (0.579), aLR (0.642), CART (0.579), and CIT (0.584), with XGBoost having a higher (0.763) AUC. However, in the post-2018 predictive analysis, aLR outperformed XGBoost (AUC 0.613 vs. 0.586). The interpretable ML models confirm the significance of previously reported risk factors (recipient bilirubin and creatinine) and identify risk factors not previously reported (donor pH, potential recipient distance, and recipient transfusion), as well as clinically relevant interaction terms. CONCLUSIONS: Carefully developed interpretable ML models of one-year transplant mortality have similar predictive performance to black-box models, while identifying novel risk factors, and showing improved performance after recent listing policy changes. With appropriate validation and additional data, interpretable ML modeling may allow real-time data-driven donor selection.

Background: Adult congenital heart disease (ACHD) patients are prone to HLA-antibody formation from multiple surgeries, transfusions, and prosthetic surgical material. Females with ACHD may accrue additional, non-surgical alloantigen exposure. Whether sex modifies the impact of allosensitization on heart transplant (HT) access and outcomes in ACHD remains unknown. Methods: We retrospectively analyzed the OPTN/UNOS registry of adults with ACHD listed for first-time HT (2018-2025). Sensitization was defined by calculated panel reactive antibodies (cPRA) at listing. We tested the sex x sensitization (highly sensitized, cPRA >50%) interaction on transplant access using Fine-Gray competing-risks regression, treating transplantation as the event of interest and death or removal from the waitlist as competing events, and on post-transplant survival using multivariable Cox proportional-hazards regression, both adjusted for age at listing, mechanical support at listing, and the number of distinct prior cardiac surgery categories. Results: Among 856 candidates (38% female), females were more often highly sensitized than males (23% vs 14%; age-adjusted OR 1.81, 95% CI 1.26-2.61), even after adjusting for surgical burden. Sensitization reduced transplant access in females (84% to 71%; median wait 60 to 110 days, p < 0.001) but not males (79% vs 79%, median wait 88 vs 98 days). In adjusted Fine-Gray models, the subdistribution hazard for transplant was reduced in sensitized females (sHR 0.54, 95% CI 0.41-0.72) with no effect in males (sHR 0.96, 95% CI 0.73-1.26), and the sex x sensitization interaction was significant (interaction sHR 0.64, 95% CI 0.44-0.94, p = 0.02). Post-transplant mortality was numerically higher in sensitized than non-sensitized candidates in both sexes and the sex x sensitization interaction on 1-year mortality was not significant. The sex-asymmetric effect persisted and was more pronounced in the multiorgan candidates. Conclusions: Allosensitization is not a sex-neutral barrier to transplant in HT candidates with ACHD. Females are more sensitized and have reduced transplant access without differences in 1-year mortality. The female excess in sensitization is not accounted for by surgical burden, and the exposures responsible remain to be defined. These findings warrant a sex-aware listing strategy and further studies.

Abstract Background: Coronary artery bypass grafting (CABG) is often preferred over percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) and multivessel coronary artery disease (MVD), but whether it confers a long-term survival advantage remains unclear. Moreover, whether anatomic complexity modulates this relationship is unknown. Methods: We included 5,615 patients with diabetes and MVD revascularized with contemporary drug-eluting stents (PCI-DES; n=3,410) or CABG (n=2,205) in Alberta, Canada, between 2009 and 2019. The primary outcome was 5-year all-cause mortality. Secondary outcomes were 5-year major adverse cardiovascular events (MACE) and 10-year mortality and MACE in an earlier-era subcohort of 2,103 patients. Inverse probability of treatment weighting with Cox proportional hazards models was used. Interactions between revascularization, Duke Jeopardy Score (DJS), and clinical presentation (stable angina, unstable angina/NSTEMI, or STEMI) were examined. Results: Five-year all-cause mortality did not differ between PCI-DES and CABG (HR, 1.14; [95% CI,0.99-1.31]; P=0.08). However, PCI-DES was associated with a higher 5-year MACE (HR, 1.23; [95% CI,1.10-1.38]; P=0.0004), but lower 10-year all-cause mortality compared to CABG (HR,0.85; [95% CI,0.72-0.99]; P=0.04) with no difference in MACE (HR, 0.97; 95 % CI: 0.85-1.11; P=0.68). Anatomic complexity modified these findings, with lower 5-year mortality after CABG only at higher DJS (Pinteraction=0.003), and lower 10-year mortality after PCI-DES only at lower DJS (Pinteraction<0.0001). Conclusions: In patients with diabetes and MVD, 5-year all-cause mortality did not differ significantly between groups, although PCI-DES was associated with higher 5-year MACE rates. At 10 years, multivessel PCI-DES was associated with lower 10-year mortality and no difference in MACE. Effects were modified by anatomic complexity, favouring CABG at higher DJS and PCI-DES at lower DJS. Our findings should be factored in when contemplating a revascularization strategy in diabetes with MVD.

BACKGROUND: Because of the high mortality rate associated with fulminant myocarditis (FM), there is limited evidence regarding the prognostic efficacy of endomyocardial biopsy (EMB). In this study, we aimed to evaluate the influence of EMB in the early phase after admission on treatment and prognosis in FM using a large-scale nationwide registry in Japan. METHODS: Patients with FM who required catecholamine or mechanical circulatory support between 2012 and 2017 from 235 hospitals across Japan were included. The primary outcome of death or heart transplantation within 90 days according to performance of early EMB were determined using Kaplan-Meier and Cox regression analyses. Factors associated with performance of early EMB, and subsequent medical treatment were analyzed. RESULTS: The median age of 736 patients with clinical FM was 56 years, and 407 patients (55%) received EMB. Most EMB (89%) were performed during the early phase (within 5 days of admission) and 63% were performed on the first day of admission. The prognosis of FM patients who underwent EMB was more favorable than that of those who did not based on the landmark analysis (log-rank test, P=0.04). Factor analysis demonstrated that FM patients who underwent EMB had a lower left ventricular ejection fraction, higher incidence of cardiogenic shock on admission, and higher rate of early mechanical circulatory support, as well as early initiation of corticosteroids and guideline-directed medical therapy (GDMT) for heart failure. Absence of any GDMT was associated with a less favorable prognosis on multivariate analysis (hazard ratio, 4.34 [95% CI, 3.14?6.01]; P<0.0001). CONCLUSIONS: Although performing EMB in the early phase after admission depends on disease severity in FM patients, it is associated with early initiation of advanced medical treatment and may contribute to improving the prognosis.

Background: Growth differentiation factor 15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Our study evaluated the temporal evolution of GDF-15 in the acute phase and its association with recurrent ischemic events. Methods: Serum samples were collected from patients with NSTE-ACS at admission and at 1 and 3 hours after admission. GDF-15 levels, along with other prognostic biomarkers, NT-proBNP and hs-cTnT, were measured. Spearman rank-correlation coefficients and linear regression models were used to identify the variables associated with GDF-15 levels at admission and with their temporal changes. Associations between GDF-15 and clinical outcomes were evaluated using Cox proportional hazards models. To assess incremental prognostic value, the areas under the curve (AUC) were calculated for each model. Results: GDF-15 levels showed a slight increasing trend within 3 hours of admission. The 1-hour change in GDF-15 was correlated with hs-cTnT changes. Increased 1-hour GDF-15 levels, compared with the admission levels, were associated with a higher risk of recurrent ischemic events during the 1-year follow-up (1.9% vs. 17.5%, P =0.019) and were an independent predictor after adjusting for established clinical variables and biomarkers (adjusted hazard ratio, 1.71 (1.28 to 228.75), P =0.03). Furthermore, serial measurements of GDF-15 provided additional prognostic information beyond traditional risk factors. Conclusions: Serial measurements of GDF-15 of NSTE-ACS patients provided independent and incremental prognostic value for predicting recurrent ischemic events. These findings support the potential utility of GDF-15 as a dynamic biomarker for early risk stratification in the acute management of NSTE-ACS.

BACKGROUND: The revised 2018 AHA/ACC guidelines introduced the Adult Congenital Heart Disease Anatomic and Physiologic classification (ACHD-AP) to better categorize disease severity and prognosis in the ACHD population. The ACHD-AP has not been rigorously studied as a perioperative prediction tool. OBJECTIVE: We aimed to assess the accuracy of the ACHD-AP classification in predicting perioperative morbidity and mortality. METHODS: This retrospective cohort study included 295 ACHD patients at a single academic institution between 2018 to 2022. Patients were identified by the STS congenital surgery registry and had undergone a congenital surgical procedure. The primary outcome was overall mortality. Secondary outcomes included short-term post-operative morbidity and comparison of the ACHD-AP score to other existing surgical mortality risk scores. Kaplan-Meier and area under the curve (AUC) of Receiver Operating Characteristic curves were used to evaluate mortality. Logistic regression was used to compare short-term morbidity. RESULTS: A total of 295 patients were included with a median age of 30 years (interquartile range 21-41 years) and 52% were female. There was a total of 14 deaths with 5 (2%) early post-operative deaths and 9 (3%) long-term deaths. By increasing anatomy complexity, overall mortality was 0%, 4% (n=10), and 8% (n=4), respectively. By increasing physiologic severity, overall mortality was 0%, 3% (n=2), 4% (n=7), and 14% (n=5). Moderate and complex anatomy trended towards increased mortality but were not statistically significant (p-value > 0.9). More severe physiology scores predicted increased mortality (p-value = 0.02). Higher physiologic or anatomic complexity scores were associated with longer post-operative length of stay (>5 days). The ACHD-AP AUC was 0.711 for mortality, which was comparable to the Adult Congenital Heart Surgery (ACHS) score (AUC 0.798) and better than the PEACH score (AUC 0.575). CONCLUSION: The ACHD-AP score revealed comparable or better predictive power to existing risk models. Worsening physiologic and anatomy scores were associated with worse post-operative outcomes. Further prospective studies are needed to validate the ACHD-AP score as a prognostic factor for patients undergoing ACHD surgery.

Introduction. Extracorporeal cardiopulmonary resuscitation (ECPR) can support patients who fail to respond to standard resuscitation for out-of-hospital cardiac arrest (OHCA) allowing further time for critical interventions and patient recovery. Although the majority of patients with refractory OHCA have coronary artery disease, the role of emergent percutaneous coronary intervention (PCI) is not clear. We evaluated the effect of PCI on survival to hospital discharge (SHD) in a contemporary cohort of patients with OHCA receiving ECPR. Methods. We performed a retrospective study using data from the Extracorporeal Life Support Organization (ELSO) registry. We included patients ?18 years with OHCA due to a presumed cardiac etiology or an initial shockable rhythm who received ECPR from January 2020 to December 2023. Our primary outcome was SHD. We used inverse probability weighted matching to estimate the average treatment effect of PCI on SHD. We also performed a sensitivity analysis of patients most likely to benefit from PCI (witnessed arrest and no return of spontaneous circulation after five minutes of cardiopulmonary resuscitation. Results. Of 1336 OHCA patients receiving ECPR, 1131 were included in the final analysis after exclusions for age (n=31) and presumed non-cardiac or initial non-shockable rhythm (n=174). The median age was 55 years (IQR 44-62) and most patients were male (n=901, 80%). Twenty-one percent (n=243) received PCI; those patients who received PCI were slightly older (58 [IQR 48-63] vs 53 [IQR 42-62]) and more often male (n=212 [87%] vs n=689 [78%]). In the primary analysis, we found no significant difference in SHD for patients who received PCI compared to those who did not receive PCI (-3.56%, 95% CI -10.31 to 3.19; p-value 0.301). In our sensitivity analysis, we also did not find a significant difference in SHD for patients who received PCI compared to those who did not receive PCI (-4.52%, 95% CI -12.42 to 2.46; p-value 0.246). Conclusion. In our registry-based study of refractory OHCA patients receiving ECPR, emergent PCI was not associated with a significant improvement in SHD.

Background: CPR is the primary intervention for cardiac arrest, and the mortality trends before and after the pandemic remain are not fully understood. Methods: This cross-sectional study used the National Inpatient Sample (NIS) database from 2016-2022 and International Classification of Diseases, Tenth Revision (ICD-10) codes to evaluate the mortality trend for adult patients undergoing CPR after in-hospital cardiac arrest (IHCA). Primary exposures were calendar year, demographics, socioeconomic factors, and hospital characteristics. Multivariable weighted logistic regression was performed to identify predictors of mortality after CPR for IHCA. Results: Among 612,930 weighted adult hospitalizations undergoing CPR for IHCA between 2016 and 2022, overall in-hospital mortality was 67.8%. Risk-adjusted mortality declined through 2019 before increasing sharply during the COVID-19 pandemic, peaking in 2021 and remaining above pre-pandemic levels in 2022. Compared with 2016, admission in 2020 (aOR 1.18, 95% CI 1.12-1.25; p<0.001) and 2021 (aOR 1.26, 95% CI 1.19-1.33; p<0.001) was independently associated with higher mortality, whereas admission in 2019 was associated with lower mortality (aOR 0.89, 95% CI 0.84-0.95; p<0.001). Higher mortality was also associated with increasing age (aOR 1.01 per year; p<0.001), female sex (aOR 1.05, 95% CI 1.02-1.08; p<0.001), Black (aOR 1.14, 95% CI 1.10-1.18; p<0.001) and Hispanic race/ethnicity (aOR 1.20, 95% CI 1.15-1.26; p<0.001), and self-pay insurance (aOR 1.62, 95% CI 1.51-1.74; p<0.001). Protective factors included private insurance (aOR 0.91, 95% CI 0.87-0.94; p<0.001), residence in the highest income quartile (aOR 0.91, 95% CI 0.87-0.94; p<0.001), and treatment at private, non-profit hospitals (aOR 0.89, 95% CI 0.85-0.94; p<0.001). Conclusion: This large nationwide patient database analysis demonstrates that mortality following CPR for IHCA declined before the COVID-19 pandemic but increased during 2020, remaining above pre-pandemic levels through 2022. Independent predictors of mortality reveal socioeconomic disparities in mortality outcomes.

Importance Evolocumab reduces major adverse cardiovascular events (MACE) in patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) and in patients at high cardiovascular (CV) risk but without a prior myocardial infarction (MI) or stroke. While evolocumab is shown to be cost-effective in clinically evident ASCVD, emerging CV outcomes evidence and newer guideline recommendations warrant assessment in patients at high CV risk without a prior MI or stroke. Objective To evaluate the cost-effectiveness of evolocumab added to standard therapy compared with standard therapy alone in patients at high CV risk without a prior MI or stroke, as represented by the VESALIUS-CV trial. Design, Setting, and Participants A previously published Markov cohort state-transition model was adapted to simulate VESALIUS-CV patients over a lifetime horizon. Health states included high-risk without a prior MI or ischemic stroke (IS), non-fatal MI, non-fatal IS, post-MI, post-IS, CV death, and non-CV death. Revascularization (RV) was modeled as a procedure with associated costs. The base case considered a US payer perspective and CV risk reduction inputs from evolocumab CV outcomes trials, including VESALIUS-CV, FOURIER, and FOURIER-OLE. Three scenario analyses were evaluated. Scenario 1 retained the US payer perspective and applied CV risk reduction estimates based on the Cholesterol Treatment Trialists' (CTT) Collaboration 2010 meta-analysis. Scenarios 2 and 3 adopted a US societal perspective, using evolocumab CV outcomes trial-based and 2010 CTT Collaboration-based risk reduction estimates, respectively. Main Outcomes and Measures The model outcomes included MACE (defined as MI, IS, or CV death), RV procedures, total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Results In the base case, at the current direct-to-patient price of $3,107 per year, evolocumab added to standard therapy was associated with lifetime reductions of 0.24 MACE and 0.17 RV procedures per person, incremental costs of $24,430, incremental QALYs of 0.34, and an ICER of $71,162 per QALY gained. Evolocumab remained cost-effective across all evaluated scenarios, with ICERs of $42,094, $51,160, and $20,152 per QALY in Scenarios 1, 2, and 3, respectively. Conclusions and Relevance In patients at high CV risk without a prior MI or stroke, evolocumab added to standard therapy was projected to improve CV outcomes and quality-adjusted survival. At the current direct-to-patient price of $3,107 per year, evolocumab was cost-effective in the base-case analysis, with an ICER of $71,162 per QALY gained, and remained cost-effective across scenario analyses, with ICERs ranging from $20,152 to $51,160 per QALY. These estimates were substantially below the $120,000 per QALY threshold defined in the 2025 American Heart Association/American College of Cardiology cost/value methodology statement.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are indicated for weight reduction and offer cardiometabolic health benefits, yet there is little real-world evidence regarding their association with healthcare resource utilization (HCRU) and costs for Medicare Advantage (MA) beneficiaries with heart failure and obesity. Methods: We used a prevalent new-user study design and the Humana Healthcare Research database to identify MA beneficiaries with heart failure (HF) and obesity receiving standard HF therapy or HF therapy + newly initiating GLP-1 RA between January 1, 2022, and December 31, 2023. We observed adjusted, one-year mean difference in all-cause and heart failure-related HCRU. Results: In our cohort of 4,677 matched pairs (mean age 72 years, male: 41%), one-year, adjusted risk ratio (RR) for HF therapy + GLP-1 RA vs HF therapy was 0.89 (95% CI: 0.84 ? 0.93) for all-cause inpatient utilization, 0.88 (95% CI: 0.82 ? 0.94) for avoidable hospitalizations, and 0.99 (95% CI: 0.95 ? 1.03) for emergency department visits. For individuals receiving HF therapy + GLP-1 RA vs HF therapy, the mean difference was 30.6% (95% CI: 26.7% ?34.7%) for all-cause total costs, 105.9% (95% CI: 99.1% ?112.9%) for pharmacy costs, and ?4.7% (95% CI: ?8.7% to ?0.6%) for medical costs. HF-related HCRU measures were lower among beneficiaries augmenting HF therapy with GLP 1 RA vs individuals receiving HF therapy alone. Conclusions: Among MA beneficiaries with heart failure and obesity, the addition of GLP-1 RA to standard heart failure therapy reduced the likelihood of inpatient admissions or avoidable hospitalizations compared with HF therapy alone.

Background Hospitalizations and mortality due to heart failure (HF) are rising in rural areas. However, inpatient outcomes for young adults with HF are not well understood. We aimed to compare in-hospital mortality, advanced procedure utilization, length of stay, and total charges among rural and urban HF patients ages 18-45. Methods We analyzed hospitalizations from the National Inpatient Sample (2016-2022), categorizing discharges as rural (National Center for Health Statistics [NCHS] 5-6), small and medium metropolitan (NCHS 3-4), and urban (NCHS 1-2). Generalized estimating equations were used to model outcomes and adjust for demographics, comorbidities, and hospital characteristics. Outcomes are reported as adjusted rate (aIRRs) or risk ratios (aRRs) with 95% confidence intervals. Results Among 79,258 HF hospitalizations among young adults, 45,075 and 10,722 were for patients from urban and rural areas, respectively. Rural patients had higher rates of in-hospital mortality (1.6% vs. 1.2%; aIRR = 1.28, 95% CI = 1.05, 1.56, p = 0.043), advanced cardiac procedure utilization (15.0% vs. 14.8%; aIRR = 1.19, 95% CI = 1.11, 1.28, p < 0.001), and longer hospital stays (aIRR = 1.10, 95% CI = 1.05, 1.14, p = 0.003). Small and medium metropolitan residents had similar outcomes to urban residents. In interaction analyses, the association between rural-urban residence and mortality differed by race (pint = 0.003) and payer type (pint < 0.001). Conclusions Young adults in rural areas may be prone to poor outcomes following hospitalization for HF. Strategies to identify rural adults at risk for HF and provide affordable and timely care may improve disparities.

Background: Optimal arterial oxygen targets after return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) remain uncertain. We examined whether arterial oxygen tension on the first arterial blood gas after ROSC is associated with neurological or survival outcomes. Methods: Using the Japanese Association for Acute Medicine OHCA Registry, we retrospectively studied pediatric patients (<18 years) with OHCA in whom ROSC was confirmed at or after hospital arrival. Patients were categorized by PaO? on the first arterial blood gas after ROSC as normoxemia (60?200 mmHg) or hyperoxemia (>200 mmHg). Missing covariate data were handled using multiple imputation, and associations were estimated using inverse probability-weighted logistic regression. Outcomes were favorable neurological status at 30 days, defined as a Pediatric Cerebral Performance Category score of 1?3, and 30-day survival. Multiple sensitivity analyses were performed, including analyses using an alternative PaO? threshold, restricting the timing of PaO? measurement, and excluding extracorporeal cardiopulmonary resuscitation cases. Results: A total of 189 patients were included (95 normoxemia, 94 hyperoxemia). A favorable neurological outcome occurred in 21 of 95 (22.1%) normoxemia and 13 of 94 (13.8%) hyperoxemia patients, and 30-day survival in 40 of 95 (42.1%) and 42 of 94 (44.7%), respectively. After weighting, covariate balance was achieved with standardized mean differences below 0.1. Hyperoxemia was not significantly associated with favorable neurological outcome (adjusted odds ratio [aOR] 0.94, 95% confidence interval [CI] 0.49?1.77) or 30-day survival (aOR 1.49, 95% CI 0.88?2.54). Sensitivity analyses yielded consistent results. Conclusions: Early hyperoxemia after ROSC was not significantly associated with neurological or survival outcomes in pediatric out-of-hospital cardiac arrest. These findings suggest that a single early PaO? measurement may be insufficient to characterize the clinical impact of oxygen exposure after resuscitation. Future research should focus on phase-specific and individualized oxygen management incorporating serial physiological assessment.

Background: Adults with congenital heart disease (ACHD) represent a rapidly expanding population with evolving mortality patterns. Despite improved survival, excess mortality persists. Objective: To evaluate the incidence, causes, and predictors of mortality in a contemporary ACHD cohort. Methods: We performed a retrospective cohort study of adults (?18 years) first evaluated at Mayo Clinic from 2002?2023. Baseline clinical, imaging, and electrocardiographic data were analyzed. Vital status was determined using institutional records and the Accurint national mortality database. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate mortality and identify independent predictors of mortality Results: A total of 7,678 ACHD patients were included, with median age of 36.8 years and median follow-up of 11.4 years. During 78,768 patient-years of follow-up, 1,116 patients died (median age at death 57.2 years), corresponding to an annual mortality rate of 1.4%. The cumulative rate of all-cause mortality at 5, 10, 15, and 20 years was 6.9%, 12.0%, 19.0%, and 26.2%, respectively. When stratified by CHD complexity, the annual death rate in patients with severe CHD (2.4%/year) was twice that of patients with moderate or mild CHD (both 1.2%/year). Older age and ACHD subtypes, specifically, cyanotic heart disease (HR 3.9, 95% CI 2.9?5.3) and Fontan physiology (HR 3.2, 95% CI 2.3?4.4), were strongly associated with increased mortality. Additional independent predictors included male sex, ventricular dysfunction, advanced NYHA class, prior heart failure hospitalization, hypertension, smoking, coronary artery disease, renal dysfunction, and abnormal hemoglobin levels. Cardiovascular causes accounted for 57.7% of deaths with known etiology, predominantly heart failure (48.9%) and sudden cardiac death (21.9%), while non-cardiovascular causes were driven mainly by infection and malignancy. Conclusions: In this large contemporary ACHD cohort, mortality was driven by ventricular dysfunction, heart failure, and systemic end-organ involvement in addition to the underlying congenital anatomy. Both cardiovascular and non-cardiovascular causes contributed significantly to mortality. These findings underscore the need for comprehensive multidisciplinary ACHD care focused on early recognition of cardiac functional decline, management of acquired comorbidities, and end-organ dysfunction.

Background: Percutaneous mechanical circulatory support (pMCS) is increasingly used in critically ill patients, yet its value in relation to cost and outcomes remains unclear. We evaluated national variation in utilization, outcomes, and cost, and introduced a value of care framework integrating risk-adjusted outcomes and expenditures. Methods: We performed a retrospective cohort study using the National Inpatient Sample to identify non-elective hospitalizations of critically ill patients undergoing intra-aortic balloon pump (IABP) or percutaneous left ventricular assist device (pLVAD) placement using ICD-10 codes. Multivariable logistic regression and generalized linear models were used to estimate expected outcomes and costs. Observed-to-expected (O/E) ratios were calculated, and a value index was derived to compare procedural strategies. Results: A total of 57,910 weighted hospitalizations were included (IABP 78%, pLVAD 22%). In-hospital mortality exceeded 30% across regions. Significant regional variation was observed, with the West demonstrating the highest costs and the Midwest the lowest (p<0.001). Mean hospital charges were higher for pLVAD compared with IABP ($403,731 vs $320,769). Both strategies achieved outcomes better than expected after risk adjustment (O/E 0.92); however, costs were higher than expected for both, with greater relative cost inflation observed for IABP (O/E 1.41) and higher absolute costs for pLVAD. In value-of-care analysis, IABP was associated with lower cost and comparable outcomes, while pLVAD demonstrated higher cost without proportional outcome improvement. Conclusion: Substantial variation exists in the cost, outcomes, and value of pMCS strategies. While both IABP and pLVAD achieve favorable risk-adjusted outcomes, pLVAD is associated with higher costs without commensurate clinical benefit.

Background: When intravenous insulin is stopped in critically ill patients, the basal insulin dose that balances rebound hyperglycemia against hypoglycemia is uncertain, because randomized trials were small and not designed to quantify this trade-off. We examined how the first glargine dose, relative to the preceding intravenous insulin requirement, was associated with both outcomes. Methods: In this retrospective cohort study of the Medical Information Mart for Intensive Care IV database (2008-2022), we included transitions from intravenous insulin infusions of at least 6 hours to subcutaneous glargine in adults without diabetic ketoacidosis or hyperosmolar hyperglycemic state. The exposure was the ratio of the first glargine dose to 24 times the mean infusion rate over the final 6 hours. The primary outcomes, rebound hyperglycemia (glucose >180 mg/dL within 24 hours) and hypoglycemia (glucose <70 mg/dL within 48 hours) during intensive care unit follow-up, were analyzed with multivariable Cox models after multiple imputation. Results: Among 6,220 transitions in 5,924 patients (87.5% after cardiac surgery), the median ratio was 0.41 (interquartile range 0.30-0.46). Kaplan-Meier cumulative incidences were 44.4% for rebound hyperglycemia (2,109 events) and 6.4% for hypoglycemia (211 events). Each 0.1 increase in the ratio was associated with less rebound hyperglycemia (hazard ratio 0.96, 95% confidence interval 0.93-0.99) and more hypoglycemia (1.11, 1.04-1.18), consistently across 21 sensitivity analyses. Rebound within the first 6 hours (57.6% of events) was not associated with the ratio (0.99, 0.95-1.02), whereas later rebound was (0.91, 0.86-0.96). Standardized to the cohort, a ratio of 0.60 versus 0.40 corresponded to 2.7 (0.6-4.9) fewer rebound and 1.7 (-0.2 to 3.5) more hypoglycemia episodes per 100 transitions. In secondary analyses, rebound was less frequent with glargine given at least 2 hours before discontinuation (0.86, 0.77-0.96) and more frequent with an oral diet (1.49, 1.30-1.71). Conclusions: In critically ill adults, mostly after cardiac surgery, higher glargine doses relative to the preceding intravenous requirement were associated with less rebound hyperglycemia after the first 6 hours and more hypoglycemia, a gradual trade-off. Which basal fraction is preferable depends on the weight given to each outcome; a randomized trial including the guideline-implied fraction of about 0.30 is warranted.

Background: Rates of atrial fibrillation (AF) are lower in Black compared to White Americans. Socioeconomic disadvantage and reduced healthcare access may contribute to lower observed AF incidence in Black populations due to underdiagnosis and underascertainment. Therefore, we evaluated the association of socioeconomic status and healthcare access with AF incidence in a cohort of Black Americans. Methods: 3,240 participants from the Jackson Heart Study, which recruited Black adults from the Jackson metropolitan area in 2000-2004, were followed up through 2016 for incident AF. Socioeconomic position (education and income) and healthcare access (insurance status, difficulty obtaining care, trust in providers, and satisfaction with care) were assessed at baseline. AF was ascertained from study electrocardiograms at baseline and exam 3 and self-reported physician diagnosis at annual follow-up surveys. Multivariable Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between exposure variables and AF incidence adjusting for potential confounders. Results: During a mean follow-up of 11.5 years, 817 incident AF cases were identified. Higher educational attainment and income were associated with a reduced risk of AF. Compared with participants who had less than a high school education, those who attended trade or vocational school or college had an 18% lower estimated hazard of AF (HR 0.82, 95% CI 0.67, 1.02). Likewise, participants in the highest income category had a 39% lower estimated hazard of AF (HR 0.61, 95% CI 0.47, 0.78) compared with those in the lowest. Easier access to healthcare and greater satisfaction with received healthcare were also associated with lower AF risk. Conclusion: Higher socioeconomic status and better healthcare access were associated with lower risk of AF in a cohort of Black Americans. These findings do not support a simple explanation in which socioeconomic disadvantage and poorer healthcare access lead to lower observed AF incidence through underascertainment within Black adults.