Circulation

BACKGROUND: Mechanical stress on the heart, such as high blood pressure, initiates inflammation and causes hypertrophic heart disease. However, the regulatory mechanism of inflammation and its role in the stressed heart remain unclear. IL-1β (interleukin-1β) is a proinflammatory cytokine that causes cardiac hypertrophy and heart failure. Here, we show that NLRP3 (neural signals activate the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3) inflammasome for IL-1β production to induce adaptive hypertrophy in the stressed heart...

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2...

BACKGROUND: Cardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes (CMs). However, certain animals readily regenerate lost myocardium through a process involving dedifferentiation, which unlocks their proliferative capacities. METHODS: We bred mice with inducible, CM-specific expression of the Yamanaka factors, enabling adult CM reprogramming and dedifferentiation in vivo. RESULTS: Two days after induction, adult CMs presented a dedifferentiated phenotype and increased proliferation in vivo...

BACKGROUND: Autoimmunity is increasingly recognized as a key contributing factor in heart muscle diseases. The functional features of cardiac autoimmunity in humans remain undefined because of the challenge of studying immune responses in situ. We previously described a subset of c-mesenchymal epithelial transition factor (c-Met)-expressing (c-Met+ ) memory T lymphocytes that preferentially migrate to cardiac tissue in mice and humans. METHODS: In-depth phenotyping of peripheral blood T cells, including c-Met+ T cells, was undertaken in groups of patients with inflammatory and noninflammatory cardiomyopathies, patients with noncardiac autoimmunity, and healthy controls...

BACKGROUND: Cross-talk between sterol metabolism and inflammatory pathways has been demonstrated to significantly affect the development of atherosclerosis. Cholesterol biosynthetic intermediates and derivatives are increasingly recognized as key immune regulators of macrophages in response to innate immune activation and lipid overloading. 25-Hydroxycholesterol (25-HC) is produced as an oxidation product of cholesterol by the enzyme cholesterol 25-hydroxylase (CH25H) and belongs to a family of bioactive cholesterol derivatives produced by cells in response to fluctuating cholesterol levels and immune activation...

BACKGROUND: Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. METHODS: VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 ( Vefgr2 Y949F ) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure...

BACKGROUND: Identifying genetic variants which impact the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. We observed that C57Bl6/NCR (B6N) mice have a marked increase in cardiomyocyte S-phase activity following permanent coronary artery ligation as compared to infarcted DBA/2J (D2J) mice. METHODS: Cardiomyocyte cell cycle activity post-infarction was monitored in D2J, (D2J x B6N)-F1 and [(D2J x B6N)-F1 x D2J] backcross mice via bromodeoxyuridine or 5-ethynyl-2' -deoxyuridine incorporation, using a nuclear-localized transgenic reporter to identify cardiomyocyte nuclei...

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Telehealth enables the remote delivery of health care through telecommunication technologies and has substantially affected the evolving medical landscape. The COVID-19 pandemic accelerated the utilization of telehealth as health care professionals were forced to limit face-to-face in-person visits. It has been shown that information delivery, diagnosis, disease monitoring, and follow-up care can be conducted remotely, resulting in considerable changes specific to cardiovascular disease management. Despite increasing telehealth utilization, several factors such as technological infrastructure, reimbursement, and limited patient digital literacy can hinder the adoption of remote care...

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BACKGROUND: Coronary artery calcium (CAC) can be identified on non-gated chest CTs, but this finding is not consistently incorporated into care. A deep learning algorithm enables opportunistic CAC screening of non-gated chest CTs. Our objective was to evaluate the impact of notifying clinicians and patients of incidental CAC on statin initiation. METHODS: NOTIFY-1 was a randomized quality improvement project in the Stanford healthcare system. Patients without known atherosclerotic cardiovascular disease (ASCVD) or prior statin prescription were screened for CAC on a prior non-gated chest CT from 2014-2019 using a validated deep learning algorithm with radiologist confirmation...

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a key pharmacotherapy in heart failure (HF) with both reduced and preserved ejection fraction. The benefit of other HF therapies may be modified by sex, but whether sex modifies the treatment effect and safety profile of SGLT2 inhibitors remains unclear. Our analyses aim to assess the impact of sex on the efficacy and safety of dapagliflozin. METHODS: In a pre-specified patient-level pooled analysis of DAPA-HF and DELIVER, clinical outcomes were compared by sex (including the composite of cardiovascular [CV] death or worsening HF events; CV death; all-cause death, total events (first and recurrent HF hospitalization and CV death), and Kansas City Cardiomyopathy Questionnaire [KCCQ] scores) across the spectrum of left ventricular ejection fraction (EF)...

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Background: Long term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention (PCI) are unknown. The HOST-EXAM Extended study reports the post-trial follow-up results of the original HOST-EXAM trial. Methods: From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after PCI with drug-eluting stents (DES) were randomly assigned in a 1:1 ratio to receive clopidogrel 75mg once daily or aspirin 100mg once daily...

Background: Breast cancer (BC) survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 early-stage BC patients scheduled for AC to determine if 12-months of exercise training (ExT) could attenuate functional disability (primary endpoint), improve cardiorespiratory fitness (VO2 peak) and prevent cardiac dysfunction. Methods: Women aged 40-75 years with stage I-III BC scheduled for AC were randomized to 3-4 days/wk of aerobic and resistance ExT for 12-months (n = 52) or usual care ([ UC ], n = 52)...

No abstract text is available yet for this article.

Background: The ISCHEMIA trial compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes over a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy (INV) added to guideline-directed medical therapy or a conservative strategy (CON). Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included...

Background: Non-vitamin K oral anticoagulants (NOACs) have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of NOACs in patients on hemodialysis is not well known. Methods: From June 2017 until May 2022, the investigator-initiated, prospective, randomized, open, blinded outcome assessment 'A Safety Study Assessing Oral Anticoagulation with ApiXAban versus Vitamin K-Antagonists in Patients with Atrial Fibrillation and End-Stage Kidney Disease on Chronic HemoDIAlysis Treatment' (AXADIA) trial randomized patients with AF on chronic hemodialysis to either apixaban 2...

BACKGROUND: There is no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and CHA2 DS2 -VASc score ≥2. Patients were randomized 1:1 to apixaban 5mg twice daily (2...

Background: Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care following percutaneous coronary intervention (PCI). However, some adverse non-cardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retain the antithrombotic efficacy, but its combination with a P2Y12 inhibitor is still lack of randomized clinical trial (RCT) evidence...