European Heart Journal Open最新文献

Aims: α_v integrins are implicated in fibrosis in a number of organs through their ability to activate TGF-β. However their role in vascular fibrosis and collagen accumulation is only partially understood. Here we have used α_v conditional knockout mice and cell lines to determine how α_v contributes to vascular smooth muscle cell (VSMC) function in vascular fibrosis and the role of TGF-β in that process.

Methods and results: Angiotensin II (Ang II) treatment causes upregulation of α_v and β₃ expression in the vessel wall, associated with increased collagen deposition. We found that deletion of α_v integrin subunit from VSMCs (α_v ^SMKO) protected mice against angiotensin II-induced collagen production and assembly. Transcriptomic analysis of the vessel wall in α_v ^SMKO mice and controls identified a significant reduction in expression of fibrosis and related genes in α_v ^SMKO mice. In contrast, α_v ^SMKO mice showed prolonged expression of CD109, which is known to affect TGF-β signalling. Using cultured mouse and human VSMCs, we showed that overexpression of CD109 phenocopied knockdown of α_v integrin, attenuating collagen expression, TGF-β activation, and Smad2/3 signalling in response to angiotensin II or TGF-β stimulation. CD109 and TGF-β receptor were internalized in early endosomes.

Conclusion: We identify a role for VSMC α_v integrin in vascular fibrosis and show that α_v acts in concert with CD109 to regulate TGF-β signalling.

Aims: Despite the well-established clinical benefits and strong recommendations in clinical guidelines, adherence to guideline-directed medical therapy (GDMT) is known to be insufficient. We investigated the adherence to GDMT and its impact on the 3-year clinical outcomes in patients with acute myocardial infarction (AMI).

Methods and results: Source data were obtained from KAMIR-NIH, a Korean multi-centre observational registry. GDMT was defined according to the ACC/AHA Class I recommendations. Adherence to GDMT was assessed at discharge and every year thereafter. The differences in clinical characteristics between patients receiving and those not receiving GDMT were adjusted using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary endpoint was major adverse cardiovascular events (MACE), which was a composite of all-cause death and non-fatal MACE, including myocardial infarction (MI), revascularization, or stroke. Of 12 815 patients, GDMT adherence was 70.2% at discharge, and decreased gradually into 54.6% at 3-year. GDMT at discharge was associated with lower MACE risk in the unadjusted analysis [hazard ratio (HR) = 0.51, 95% confidence intervals (CI) = 0.47-0.55, P < 0.001] and also in the PSM- or IPTW-adjusted analyses (HR = 0.77, 95% CI = 0.69-0.86; HR = 0.79, 95% CI = 0.72-0.86; P < 0.001, all). These findings were replicated in the 1-year or 2-year landmark analyses (HR = 0.58 to 0.82, P < 0.01, all).

Conclusion: Adherence to GDMT was sub-optimal among patients with AMI in Korea. As the adherence to GDMT was associated with a lower incidence of MACE during 3-year follow-up, the maintenance of long-term GDMT might be crucial for patients with AMI.

Aims: Patients with chest pain and normal coronary angiogram [angina with normal coronary arteries (ANOCA)] constitute a therapeutic problem with considerable functional limitation and reduced quality of life. The aims of the current pilot study were to (i) explore if a structured aerobic high-intensity interval training (HIT) program for 12 weeks was feasible in patients with ANOCA, and (ii) to assess mechanisms related to symptoms in this population.

Methods and results: Sixteen patients with ANOCA underwent a 3-month aerobic HIT program with one-to-one monitored exercise sessions on treadmill in a 4 min × 4 manner, three times a week. Four patients served as controls. Coronary flow velocity reserve (CFVR) transthoracic Doppler, flow-mediated vasodilation (FMD) and VO_2max was measured at baseline and after 12 weeks. The average attendance to training sessions was 82.3% ± 10.1 (56-94). CFVR in the training group increased from 2.50 ± 0.48 to 3.04 ± 0.71 (P < 0.001) whereas FMD increased from 4.19 ± 2.42% to 8.28 ± 2.85% (P < 0.001). Improvement in CFVR correlated with the relative improvement in FMD (R = 0.45, P = 0.047). This was associated with an increase in VO_2max from 28.75 ± 6.51 mL/kg/min to 31.93 ± 6.46 mL/kg/min (P < 0.001).

Conclusion: A 3-month program of monitored HIT was feasible, with high adherence resulting in improved functional capacity in patients with ANOCA. CFVR improved and this improvement was associated with improved FMD.

Clinicaltrialsgov identifier: NCT02905630.

Aims: Psoriasis has been associated with increased cardiovascular (CV) risk. We investigated whether markers of CV function and their change after treatment have a prognostic value for adverse outcomes.

Methods and results: In a prospective study, at baseline and after 6 months of treatment with biological agents, we assessed in 298 psoriasis patients (i) left ventricular global longitudinal strain (GLS) and (ii) carotid-femoral pulse wave velocity (PWV), to evaluate their prognostic value for major adverse cardiovascular events (MACEs), including coronary artery disease, stroke, hospitalization for heart failure, and all-cause death over a 4-year follow-up period. During follow-up, 26 (8.7%) MACEs were recorded. By univariate analysis, decreasing absolute GLS values [hazard ratio (HR): 0.73, P < 0.001], decreasing GLS change after treatment (HR: 0.53, P = 0.008), and increasing PWV values (HR: 1.16, P = 0.049) were associated with adverse outcomes. Baseline GLS and its change post-treatment remained independent predictors of adverse events after adjusting for several confounders (P < 0.05). The addition of baseline GLS and its absolute change post-treatment to SCORE2 increased Harrell's C from 0.882 to 0.941. By multivariable analysis, for each 1% increase in absolute baseline GLS values, the risk of MACE decreased by 33% and for each 1% absolute increase of GLS post-treatment compared with the baseline value, the risk of MACE decreased by 58%.

Conclusion: Global longitudinal strain has an independent and additive prognostic value to SCORE2 for adverse CV events in psoriasis, providing timely decision-making for intensive anti-inflammatory treatment and aggressive modification of risk factors to reduce CV risk.

Rheumatic heart disease (RHD) is the most common cause of valvular heart disease worldwide, affecting millions, especially in low- and middle-income countries. Multiple imaging modalities such as cardiac CT, cardiac MRI, and three-dimensional echocardiography may be utilized in diagnosing, screening, and managing RHD. However, two-dimensional transthoracic echocardiography remains the cornerstone of imaging in RHD. Criteria developed by the World Heart Foundation in 2012 sought to unify the diagnostic imaging criteria for RHD, but concerns remain regarding their complexity and reproducibility. In the intervening years, further measures have been developed to find a balance between simplicity and accuracy. Nonetheless, there remain significant unresolved problems within imaging in RHD, including the development of a practical and sensitive screening tool to identify patients with RHD. The emergence of handheld echocardiography has the potential to revolutionize RHD management in resource-poor settings, but its role as a screening or diagnostic tool is yet to be fully established. The dramatic evolution of imaging modalities over the last few decades has not addressed RHD compared to other forms of structural heart disease. In this review, we examine the current and latest developments concerning cardiac imaging and RHD.

People living with cardiac sarcoidosis (CS) are likely to have worse clinical outcomes and greater impairment on health-related quality of life (HRQoL) than other sarcoidosis manifestations. CS can result in a constellation of intrusive symptoms (such as palpitations, dizziness, syncope/pre-syncope, chest pain, dyspnoea, orthopnoea, or peripheral oedema) and/or life-threatening episodes, requiring consideration of invasive cardiac procedures for diagnosis and for the management of acute events. Additionally, the presence of multisystemic involvement and persistent non-specific sarcoidosis symptoms negatively affect HRQoL. A systematic review was undertaken to explore the impact of CS on HRQoL in adults with CS. Multiple bibliographic databases were searched for studies with HRQoL as primary or secondary outcomes in CS (PROSPERO registration: CRD42019119752). Data extraction and quality assessments were undertaken independently by two authors. From the initial 1609 identified records, only 11 studies included CS patients but none specifically reported HRQoL scores for CS patients. The average representation of CS patients was 14.5% within these cohorts (range 2-22%). The majority (73%) was conducted in single-centre tertiary care settings, and only one study (9%) included longitudinal HRQoL data. CS patients were among those sarcoidosis patients with impaired HRQoL and worse outcomes, requiring higher doses of sarcoidosis-specific therapy which contribute to further deterioration of HRQoL. Sarcoidosis studies do not incorporate stratified HRQoL scores for CS patients. While there is a need for longitudinal and multicentre studies assessing HRQoL outcomes in CS cohorts, the development of CS-specific tools is also needed.