Nassal MMJ, Smith RM, Aramendi E
… +9 more, Elola A, Jaureguibeitia X, Idris A, Daya MR, Carlson J, Aufderheide T, Nichol G, Panchal AR, Wang HE
Circulation
· 2026 May · PMID 42145111
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BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes. However, the minimum EtCO monitoring duration needed to discriminate return of spontaneous...BACKGROUND: Exhaled end-tidal carbon dioxide (EtCO) trajectory is associated with out-of-hospital cardiac arrest (OHCA) outcomes. However, the minimum EtCO monitoring duration needed to discriminate return of spontaneous circulation (ROSC) from non-ROSC remains unknown. We sought to determine the EtCO trajectory observation time required to differentiate ROSC from non-ROSC patients. METHODS: We performed a secondary analysis of the cluster-randomized Pragmatic Airway Resuscitation Trial (PART), which assessed endotracheal intubation or laryngeal tube strategies in OHCA resuscitation. We summarized mean EtCO in 1-minute epochs over the resuscitation. Cases were stratified a priori by: (1) witnessed versus unwitnessed status, and (2) initial EtCO: low (≤30 mm Hg), moderate (31-49), and high (≥50). Within each stratum, group-based trajectory modeling (GBTM) was used to identify latent EtCO trajectory classes, and patients were categorized into an upward or downward trajectory. To balance trajectory groups on baseline characteristics including age, sex, race, initial rhythm, location, and bystander CPR, we applied inverse probability of treatment weighting. We fit weighted pooled logistic regression models to estimate risk ratios (RRs) for ROSC comparing upward versus downward EtCO trajectories. Within each stratum, we identified the earliest minute when CIs between upward versus downward EtCO trajectories no longer overlapped. RESULTS: EtCO data were available for 1168 patients: 452 (38.6%) witnessed and 716 (61.1%) unwitnessed. Patients were predominantly men (63.5%), with a median age of 65 years (Q1, Q3: 53-75), majority White race (51.3%), and presenting in a nonpublic setting (85.4%). Overall ROSC was 18.2%: 30.5% of witnessed and 10.5% of unwitnessed. Among witnessed arrests, 95% CI for upward versus downward EtCO trajectories no longer overlapped at 8 minutes for low initial EtCO (RR, 3.06; 95% CI, 1.49, 6.71), 12 minutes for moderate EtCO (RR, 1.95; 95% CI, 1.23, 3.48), and 21 minutes for high EtCO (RR, 2.12; 95% CI, 1.30, 3.73). Among unwitnessed arrests, nonoverlapping CIs were first observed at 7 minutes (RR, 3.56; 95% CI, 1.53, 10.37). CONCLUSIONS: Depending on witness status and initial EtCO, between 7 and 21 minutes of monitoring are needed to reliably differentiate upward from downward EtCO trajectories during OHCA resuscitation. Dynamic EtCO trajectory monitoring may provide early prognostic information to guide resuscitation.
Abbott JD, Benatar JR, Ballantyne CM
… +12 more, Jacobs AK, Goldsweig AM, Fergusson DA, Hebert BM, Bertolet M, Simon T, Steg PG, Goodman SG, White HD, Carson JL, Brooks MM, MINT Investigators
Circulation
· 2026 May · PMID 42145087
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BACKGROUND: The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes. The Myocardial Ischemia and...BACKGROUND: The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes. The Myocardial Ischemia and Transfusion trial (MINT) randomized patients with AMI and anemia to restrictive or liberal transfusion thresholds, but sex-stratified outcomes remain undefined. The objective was to evaluate whether the clinical effect of restrictive versus liberal red blood cell transfusion strategies differs by sex in patients hospitalized with AMI and anemia. METHODS: In this prespecified secondary analysis of the MINT trial, we examined outcomes by sex and transfusion strategy. The primary outcome was 30-day composite death or MI. Secondary outcomes included heart failure, stroke, cardiac death, and 180-day mortality. Adjusted relative risks (RRs) and hazard ratios (HRs) were estimated accounting for sex differences at baseline. Interactions between sex and transfusion effects were assessed. RESULTS: There were 3504 study participants, of whom 1593 (45.4%) were women. Women received fewer transfusions on average. Primary outcome occurred in 15.4% of women and 15.4% of men and occurred in 16.5% of women and 17.1% of men in the restrictive arm, versus 14.9% and 14.2% in the liberal arm, respectively. Women had a lower 180-day mortality (11.0% versus 13.5%; =0.04). There were no statistically significant interactions between sex and transfusion strategy for the primary outcome (interaction =0.60). For 30-day cardiac death, a higher RR in men was observed in the restrictive transfusion arm (RR, 2.34; 95% CI, 1.48-3.70; interaction =0.05). CONCLUSIONS: For MINT patients with anemia and AMI, women comprised nearly half of the study population, and randomization to a restrictive or liberal transfusion strategy resulted in comparable outcomes in women and men. These findings support sex-neutral transfusion thresholds. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.
Vega RB, O'Mahony G, Barbour AM
… +26 more, Yu H, Knöchel J, Brengdahl J, Hochdörfer T, Bergenholm L, Töppner Carlsson E, Ahnmark A, Underwood CR, Rudvik A, Carter D, Laru J, Gutgsell A, Twaddle L, Garkaviy P, Bogstedt A, Hurt-Camejo E, Miliotis T, Ryaboshapkina M, Hober A, Hubbard B, Serrano-Wu M, Kaushik V, Geschwindner S, McCarthy MC, Lindén D, Rosenmeier JB
Circulation
· 2026 Jun · PMID 42137960
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BACKGROUND: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is an effective therapy for reducing low-density lipoprotein (LDL) cholesterol (LDL-C) in adults with hyperlipidemia, including heterozygous...BACKGROUND: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is an effective therapy for reducing low-density lipoprotein (LDL) cholesterol (LDL-C) in adults with hyperlipidemia, including heterozygous familial hypercholesterolemia, thereby lowering cardiovascular risk. Current PCSK9 inhibitors are injectable therapies; no oral small-molecule PCSK9 inhibitor has yet been approved. METHODS: Laroprovstat (AZD0780) is a novel small-molecule identified through structure-based design that binds to the PCSK9 C-terminal domain. The effects of laroprovstat on LDL receptor expression and LDL-C levels were assessed in vitro and in mice expressing human . Safety, tolerability, and pharmacokinetic and pharmacodynamic properties of laroprovstat were assessed in healthy participants with LDL-C ≥70 and ≤190 mg/dL after single ascending doses. Laroprovstat was also assessed in participants with LDL-C ≥100 and ≤190 mg/dL at doses of 1 mg or 30 mg versus placebo administered once daily for 28 days after a rosuvastatin 20 mg run-in treatment period. RESULTS: Laroprovstat does not inhibit the PCSK9-LDL receptor interaction but stabilizes the PCSK9 C-terminal domain, preventing lysosomal trafficking and degradation of LDL receptor. Laroprovstat increased LDL receptor expression and reduced LDL-C levels in mice expressing human . Laroprovstat displayed dose-proportional pharmacokinetics and a half-life suitable for once-daily dosing (≈40 hours). There was no clinically meaningful change in exposure when dosed with a high-fat meal compared with the fasted state (area under the plasma concentration-time curve and C geometric mean reduction of 1.15 [90% CI, 1.11-1.19] and 1.06 [90% CI, 1.00-1.13], respectively). After a rosuvastatin 20 mg 3-week run-in treatment period, laroprovstat 1 and 30 mg reduced LDL-C by 29% (95% CI, 18%-38%) and 51% (95% CI, 44%-58%) compared with baseline. Combined rosuvastatin and laroprovstat treatment resulted in a total approximate reduction in LDL-C of 70% and 80% for laroprovstat 1 and 30 mg, respectively. CONCLUSIONS: Laroprovstat was well tolerated with no safety findings of concern and may be dosed with or without food. In treatment-naïve participants with hypercholesterolemia, combined rosuvastatin 20 mg and laroprovstat 30 mg treatment led to an 80% LDL-C reduction, supporting further development of laroprovstat as the first oral small-molecule PCSK9 inhibitor in patients with hypercholesterolemia. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05384262.
Herrera-Leaño N, Celestin B, Santana EJ
… +10 more, Sandoval R, Fahed G, Khoury P, O'Sullivan JW, Kuznetsova T, Cauwenberghs N, Mahaffey KW, Douglas PS, Daubert MM, Haddad F
BACKGROUND: The 2016 American Society of Echocardiography (ASE) guidelines for left ventricular diastolic dysfunction (LVDD) classification resulted in a significant proportion of indeterminate classifications and grades...BACKGROUND: The 2016 American Society of Echocardiography (ASE) guidelines for left ventricular diastolic dysfunction (LVDD) classification resulted in a significant proportion of indeterminate classifications and grades. To address these limitations and incorporate new evidence, the ASE updated its recommendations in 2025. The impact of these revisions in community cohorts remains unclear. METHODS: We studied 1953 Project Baseline Health Study participants who underwent comprehensive transthoracic echocardiography. LVDD was classified using the 2016 and 2025 ASE recommendations. For the 2025 recommendations, fixed and age-specific thresholds were evaluated separately. We compared LVDD prevalence, reclassification patterns, associations with cardiovascular risk factors, and prognostic value for major adverse cardiovascular events over a median follow-up of 4.3 years. RESULTS: Median patient age was 50.6 years (Q1-Q3: 36.3-64.2); 56.3% of patients were female, 35.3% had hypertension, and 14.2% had diabetes. The prevalence of LVDD was higher with the 2025 recommendations than with the 2016 algorithm: fixed criteria 308 (15.8%), age-specific criteria 220 (11.3%) versus ASE 2016 154 (8.0%). Among 119 (6.1%) participants classified as indeterminate by the 2016 algorithm, the 2025 recommendations reclassified 51.2% as no LVDD and 31.8% as Grade 2 LVDD. Participants reclassified as no LVDD had event-free survival that was not statistically different from those without LVDD (=0.26), whereas those reclassified as Grade 2 had higher event rates (12.5% versus 3.8%; =0.02). Major adverse cardiovascular events occurred in 98 (5.0%) participants over the follow-up period. LVDD by all classification approaches was independently associated with major adverse cardiovascular events after adjustment for baseline risk factors. CONCLUSIONS: The 2025 ASE recommendations identified more participants with LVDD than the 2016 algorithm without indeterminate classification or grading. LVDD by the 2025 classification was significantly associated with major adverse cardiovascular events, supporting the clinical relevance of the revised framework.
BACKGROUND: Alternative indexation methods for left atrial volume (LAV) have been proposed to achieve better proportional scaling than the current standard body surface area indexation. However, there are limited data sh...BACKGROUND: Alternative indexation methods for left atrial volume (LAV) have been proposed to achieve better proportional scaling than the current standard body surface area indexation. However, there are limited data showing that these alternative indices provide long-term prognostic value in individuals with overweight or obesity. The aim of this study was to determine and compare the performance of various LAV indexation methods in predicting all-cause mortality in individuals with overweight or obesity. METHODS: We obtained data from the National Echocardiography Database Australia with linkage to mortality outcomes, selecting individuals with body mass index ≥25 kg/m and valid LAV, height, weight, and left ventricular ejection fraction. We conducted receiver operating characteristic analyses, including area under the curve calculations, to compare the performance of 9 LAV indices in predicting all-cause mortality. In addition, we performed a survival analysis between LAV and all-cause mortality. RESULTS: A total of 109 543 individuals (age 60±16 years, 47% women) were included. Indexing LAV by most methods performed similarly in predicting all-cause mortality, with areas under the curve between 0.60 and 0.62 (<0.05), except that LAV and LAV/body mass index had the lowest area under the curve with 0.600 (0.595-0.604) and 0.602 (0.597-0.606). Indexation methods also performed similarly when separated by age, sex, or follow-up duration. A mortality threshold for LAV/body surface area was observed at 34 mL/m, with no difference by sex. CONCLUSIONS: Among patients with overweight or obesity, the majority of LAV indices performed similarly in predicting all-cause mortality. Our findings support the continued use of LA volume indexed to body surface area for prognosis in this population, and the current normal range of <34 mL/m. REGISTRATION:URL: https://anzctr.org.au/Default.aspx; Unique identifier: ACTRN12617001387314.
Ruel M, Sandner S, Ponnambalam M
… +8 more, Brown C, Gaudino M, Sun L, Verma S, Poirier P, American Heart Association Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology, Council on Lifestyle and Cardiometabolic Health
Circulation
· 2026 Jun · PMID 42125794
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Coronary artery bypass grafting is a well-established, durable, and safe surgical intervention. However, coronary artery disease continues to progress after the procedure. Patients who have undergone bypass surgery prese...Coronary artery bypass grafting is a well-established, durable, and safe surgical intervention. However, coronary artery disease continues to progress after the procedure. Patients who have undergone bypass surgery present unique challenges in terms of secondary prevention resulting from the often severe and diffuse nature of their coronary disease, the complexities of their postoperative recovery, the burden of their comorbid conditions, and the importance of ensuring long-term graft patency and preventing further disease progression. New evidence and advances in secondary prevention strategies in the post-coronary bypass grafting population have emerged since the American Heart Association's 2015 scientific statement on this topic. Secondary prevention strongly correlates with improved outcomes after bypass surgery, providing the rationale and urgency for this updated scientific statement to promote evidence-based practical considerations and to improve their use.
Lalani C, Secemsky E, Song Y
… +12 more, Dong H, Kirtane AJ, Neupane S, Krishnaswamy A, Price MJ, Davies R, Frizzell JD, Kearney KE, Safirstein J, Ali ZA, Cavalcante R, Yeh RW
Circ Cardiovasc Interv
· 2026 May · PMID 42117274
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BACKGROUND: AGENT is the only coronary drug-coated balloon (DCB) approved for treatment of in-stent restenosis (ISR) to date. In this study, we describe trends in DCB use and compare characteristics and in-hospital outco...BACKGROUND: AGENT is the only coronary drug-coated balloon (DCB) approved for treatment of in-stent restenosis (ISR) to date. In this study, we describe trends in DCB use and compare characteristics and in-hospital outcomes between patients who received DCB versus alternative treatments. METHODS: We included patients in the American College of Cardiology National Cardiovascular Disease Registry CathPCI Registry who underwent percutaneous coronary intervention between April 2024 and June 2025 and received DCB, drug-eluting stent (DES), or plain old balloon angioplasty. Treatment groups were compared using standard mean differences. RESULTS: Between April 2024 and June 2025, 14 946 DCBs were used in 12 337 patients across 704 CathPCI Registry sites. The monthly rate of DCB use for ISR percutaneous coronary intervention grew from <1% to 17.5% during the study period. Of 96 452 ISR procedures performed overall, 9269 (9.61%) involved the use of DCB. DCB procedures were more likely to involve the use of specialty balloons (DCB 45.3% versus DES 17.5% versus plain old balloon angioplasty 28.3%), intravascular imaging (DCB 54.5% versus DES 35.1% versus plain old balloon angioplasty 30.9%), and atherectomy (DCB 14.9% versus DES 6.0% versus plain old balloon angioplasty 7.3%). Among patients treated with DCB, 0.4% experienced myocardial infarction, 0.7% developed cardiogenic shock, 0.2% had an ischemic stroke, and 0.9% died. DCB was separately used in 3459 of 810 483 (0.43%) non-ISR percutaneous coronary interventions. Unadjusted rates of in-hospital adverse outcomes after ISR and non-ISR DCB use were like those for DES (standard mean difference <10%). CONCLUSIONS: Real-world DCB use is increasing rapidly in the United States, driven by use in ISR lesions but also with growth among non-ISR lesions.
Fabris T, Arturi F, Buono A
… +60 more, de Biase C, Bellamoli M, Zito A, Mangieri A, Montarello N, Costa G, Alfadhel M, Koren O, Fezzi S, Bellini B, Massussi M, Scotti A, Bai L, Costa G, Mazzapicchi A, Giacomin E, Gorla R, Hug K, Briguori C, Bettari L, Messina A, Boiago M, Renker M, Garcia Gomez M, Napodano M, Fraccaro C, Nai Fovino L, Masiero G, Cardaioli F, Putortì F, Panza A, De Rosa ML, Trani C, Laterra G, Latini A, Pellegrini D, Ielasi A, Orbach A, Landes U, Rheude T, Testa L, Amat Santos I, Saia F, Favero L, Cernetti C, Chen M, Adamo M, Latib A, Petronio AS, Montorfano M, Makkar RR, Burzotta F, Barbanti M, Blackman DJ, Mylotte D, De Backer O, Tchètchè D, Maffeo D, Kim WK, Tarantini G
BACKGROUND: Evidence regarding prosthesis-patient mismatch (PPM), measured (mPPM), and predicted (pPPM), after transcatheter aortic valve replacement in bicuspid aortic valve stenosis remains limited. This study sought t...BACKGROUND: Evidence regarding prosthesis-patient mismatch (PPM), measured (mPPM), and predicted (pPPM), after transcatheter aortic valve replacement in bicuspid aortic valve stenosis remains limited. This study sought to evaluate the incidence, predictors, and prognostic implications of mPPM and pPPM in patients with Sievers type 1 bicuspid aortic valve undergoing transcatheter aortic valve replacement. METHODS: The AD-HOC registry is a retrospective, multicenter study including 781 patients with severe aortic stenosis and bicuspid aortic valve treated with transcatheter aortic valve replacement between 2016 and 2023 across 24 centers. PPM was defined according to Valve Academic Research Consortium-3 criteria. The primary outcome was all-cause mortality. RESULTS: Moderate-to-severe mPPM was more frequent than pPPM (22% versus 8%; <0.001). Balloon-expandable valves were independently associated with both mPPM and pPPM, while smaller valve size and supra-annular sizing predicted only pPPM. During a mean follow-up of 621±470 days, neither mPPM nor pPPM was associated with mortality in the overall cohort. Among patients with a small annulus (≤430 mm; n=145), pPPM occurrence was significantly higher (19% versus 5.5%; <0.001) and was associated with increased all-cause mortality, but not with cardiovascular mortality. CONCLUSIONS: In patients with Sievers type 1 bicuspid aortic valve undergoing transcatheter aortic valve replacement, pPPM occurred less frequently than mPPM and was predominantly driven by anatomic characteristics and sizing strategies. Although pPPM was associated with increased all-cause mortality among patients with small annuli, this association did not extend to cardiovascular mortality and should be considered hypothesis-generating. Further prospective investigations are warranted to better delineate the impact of anatomic constraints on clinical outcomes in this anatomically challenging subset.
Dixon DD, Lewsey SC, Contreras J
… +3 more, Shah KS, Deen J, Breathett K
Circ Heart Fail
· 2026 Jun · PMID 42117257
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Institutional and systemic practices and policies contribute to lower-quality care and adverse outcomes among diverse racial and ethnic groups and individuals with limited economic resources. There are ample opportunitie...Institutional and systemic practices and policies contribute to lower-quality care and adverse outcomes among diverse racial and ethnic groups and individuals with limited economic resources. There are ample opportunities to change the trajectory of patients with heart failure (HF) across racial and ethnic groups. Multiple studies and quality improvement initiatives have demonstrated strategies to improve the care of diverse racial and ethnic populations living with HF, yet dissemination remains limited. This state-of-the-art review examines structural racism in the context of HF, outlines evidence-based strategies for HF programs to improve access to advanced HF therapies and reduce disparities in treatment outcomes, and discusses priorities for implementation and dissemination science efforts to address structural causes of disparities in HF care.