Search Results for: Circulation

Circulation, Volume 152, Issue 1, Page 1-3, July 8, 2025.

Circulation, Volume 152, Issue 1, Page e1-e2, July 8, 2025.

Circulation, Volume 152, Issue 1, Page 4-6, July 8, 2025.

Circulation, Volume 152, Issue 1, Page 74-78, July 8, 2025.

Circulation, Volume 152, Issue 1, Page 79-80, July 8, 2025.

Circulation, Volume 152, Issue 1, Page e5-e6, July 8, 2025.

Circulation, Volume 152, Issue 1, Page e23-e23, July 8, 2025.

Circulation, Volume 152, Issue 1, Page 81-84, July 8, 2025.

Circulation, Volume 152, Issue 1, Page 58-73, July 8, 2025. The increasing demand for donor hearts presents both a critical challenge and a significant opportunity for innovation in cardiac transplantation. Advancements in immunosuppressive regimens and genetic engineering have reignited recent interest in xenotransplantation. Notably, 2 human patients have received genetically modified pig hearts under expanded-access authorization. They survived for 40 and 60 days, with xenograft failure preceding death in both cases. Concurrently, decedent studies have focused on monitoring the short-term physiological function of genetically modified cardiac xenografts in legally brain-dead recipients, representing a novel experimental paradigm for preclinical testing to help bridge the gap between nonhuman primate studies and clinical trials. These contemporary achievements build on a large body of exploratory efforts in cardiac xenotransplantation in nonhuman primates. Despite significant progress in overcoming hyperacute rejection, adaptive cellular and humoral immunological barriers remain. This review aims to critically evaluate the current advancements in xenotransplantation, to explore ongoing challenges, and to discuss the future potential of this innovative approach in addressing the growing demand for donor organs in cardiac transplantation.

Circulation, Volume 152, Issue 1, Page 7-10, July 8, 2025.

Circulation, Ahead of Print. BACKGROUND:Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)–mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions.METHODS:Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of Mtus1 in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation–mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9).RESULTS:Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific knockout of Mtus1 in mice exacerbated cardiac dysfunction after MI. Both in vitro and in vivo studies demonstrated the vital role of Mtus1A in modulating mitochondria-associated ER membranes coupling and preserving mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining ER-mitochondria connectivity.CONCLUSIONS:Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.

Circulation, Ahead of Print. BACKGROUND:Equal access to care for patients with congenital heart disease (CHD) remains unrealized globally. The ASSIST project (Academic Medical Hospitals–Local Institutions collaboration) is an ongoing national quality initiative implemented in low-resource settings in China attempting to reduce gaps in access to CHD care. This study sought to evaluate its feasibility and effectiveness.METHODS:Shanghai Children’s Medical Center, an academic medical center, has partnered with 4 local hospitals in low-resource regions to enhance local CHD programs since 2021. Comparison was made between patients receiving treatments in these 4 local hospitals before (2013–2020) versus after the ASSIST project (2021–2024). In addition, contemporaneous patients receiving treatments in Shanghai Children’s Medical Center (2021–2024) were compared with the post-ASSIST cohort of patients. The primary outcome was a composite of postoperative mortality and multiorgan dysfunction. A key secondary outcome was delayed treatment, defined as an interval of more than 6 months between the time of surgery and the time when the clinicians recommended surgery at the initial presentation.RESULTS:The analysis cohort included 11 895 pediatric patients (median age, 2.0 years [25th–75th percentile 0.7–5.0]; 5933 female [49.9%]), with 3333 cases in the pre-ASSIST group, 1566 in the post-ASSIST group, and 6996 in the Shanghai Children’s Medical Center group. Lower family educational attainment (odds ratio, 1.50 [95% CI 1.21–1.85];P

Circulation, Ahead of Print. The postacute sequelae of SARS-CoV-2, also known as Long COVID, may affect 10% to 25% of individuals diagnosed with SARS-CoV-2. More than 100 symptoms have been reported among patients with Long COVID, but almost all patients report severe fatigue, orthostatic intolerance, shortness of breath, and reductions in exercise tolerance. Emerging data suggest that cardiovascular deconditioning plays a major role in the development of this syndrome and that reductions in functional capacity among patients with Long COVID are comparable to reductions seen among individuals with cardiovascular deconditioning resulting from bed rest. Concern has been raised about the use of exercise training as part of the management strategy for patients with Long COVID. However, exercise training appropriately tailored to the patient with cardiovascular deconditioning may be an effective strategy to facilitate improvement in symptoms. This American Heart Association scientific statement provides a concise yet comprehensive overview of mechanisms contributing to development of Long COVID and methods by which exercise training may be applied to this unique patient population to alleviate symptoms and improve quality of life. In addition, methods of reintroducing exercise and return to play among athletes affected by COVID-19 are discussed.

Circulation, Ahead of Print. BACKGROUND:Evaluation of whether dyspnea has a cardiac cause is essential. Guidelines from 2016 were reported to result in a high incidence of indeterminate left ventricular (LV) filling pressure. We sought to validate a new algorithm for the estimation of LV filling pressure (LVFP) in a multicenter study, with the objective of decreasing the yield of indeterminate filling pressure and increasing accuracy.METHODS:In an observational study, echocardiography was performed in 951 patients referred for cardiac catheterization. Echocardiographic measurements included mitral inflow, pulmonary vein and tissue Doppler mitral annulus velocities, tricuspid regurgitation velocity, assessment of mean right atrial pressure, biplane LV and left atrial volumes, and LV and left atrial strain. A stepwise approach was applied in a new algorithm for estimation of LVFP, whereby pressure >15 mm Hg was considered abnormally elevated. The first step included mitral annulus early diastolic velocity (e′), the ratio of mitral early flow velocity to e′, and pulmonary artery systolic pressure. With concordant findings in all 3 variables, conclusions about LVFP could be reached. In case of discordant or incomplete variables, left atrial reservoir strain, left atrial maximum volume index, isovolumic relaxation time, and pulmonary vein flow were analyzed in a second step. In the presence of ≥1 abnormal measurement in the second step, the conclusion of elevated LVFP could be reached.RESULTS:Only 2 patients had indeterminate LVFP as per the new algorithm versus 38 applying 2016 guidelines (P

Stroke, Ahead of Print. Recently, 6 randomized controlled trials of endovascular treatment (EVT) versus medical management in anterior circulation large vessel occlusion with large-core documented significant benefit of EVT on functional outcome. Moreover, one trial reported the benefit of EVT in the large-core category (Alberta Stroke Program Early Computed Tomography Score, 0–2). These results are considered paradoxical by some as they contradict the prevailing view that the presence of a large core precludes the possibility of good outcomes following reperfusion. They, in turn, led some investigators to question the applicability of the core/penumbra model in the case of large-core stroke and even its overall validity, specifically regarding the notion that the core reliably predicts tissue infarction. Here, we discuss the trial results and propose alternative explanations for the large-core paradox. First, although EVT does improve outcomes as compared with medical management, overall outcomes remain poor in ≈80% of the treated population. Second, the assessment of core extent on imaging, particularly with computed tomography, is potentially inaccurate, especially in the early time window. Third, consistent with observational studies, some randomized controlled trial substudies suggest that the benefit of EVT in this population derives at least in part from the salvage of penumbra, which appears to have been present in a large percentage of enrolled patients. Fourth, the markedly reduced perfusion that prevails within large cores facilitates the early development of vasogenic edema. This heterogeneity of tissue injury may, in turn, lead to an overestimation of true core/neuronal death as estimated with computed tomography and magnetic resonance imaging. Assessing patients with apparent large core should consider these notions when discussing eligibility for EVT. Early reperfusion of large-core patients is expected to both target any residual penumbra and prevent the development of vasogenic edema within the severely hypoperfused areas. These considerations underscore the need for more reliable methods to identify irreversible neuronal injury inside the imaging-based estimated core.

Stroke, Ahead of Print. BACKGROUND:In acute ischemic stroke, infarcted tissue gradually becomes detectable on noncontrast computed tomography (NCCT) as a hypodensity representing vasogenic edema. We studied whether subtle NCCT density changes are also present in penumbral tissue.METHODS:This observational cohort study included patients with stroke with anterior circulation occlusions from the CRISP2 study (CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project 2) who were transferred from a primary to a comprehensive stroke center for consideration of endovascular thrombectomy. Patients received baseline NCCT and computed tomography perfusion at the referring hospital and magnetic resonance imaging at the receiving hospital. We created baseline relative NCCT images, which compare voxel density to the corresponding area in the contralateral hemisphere. We analyzed the relative density of rNCCT in the core and penumbra (based on computed tomography perfusion in referring hospitals). We also assessed the correlation between relative density and the degree of hypoperfusion in the penumbra, defined as the time-to-maximum of the tissue residue function. We studied the association between penumbral changes and functional outcomes on the full distribution of the modified Rankin Scale score at 90 days.RESULTS:From the 314 patients, 162 met inclusion criteria with a median (interquartile range) age of 73 (61–83) years, penumbra volume of 78 (52–113) mL, and core volume of 0.6 (0–13.0) mL; 54% were men. The relative density was reduced by a median of 1.8% (P