The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been exploited for the treatment of diseases. For example, EVs secreted by stem cells injected into infarcted hearts can induce recovery through the delivery of stem-cell-specific miRNAs. However, the retention of the EVs and the therapeutic effects are short-lived. Here, we show that an engineered hydrogel patch capable of slowly releasing EVs secreted from cardiomyocytes derived from induced pluripotent stem (iPS) cells reduced arrhythmic burden, promoted ejection-fraction recovery, decreased cardiomyocyte apoptosis 24 hours after infarction, and reduced infarct size and cell hypertrophy 4 weeks post-infarction when implanted onto infarcted rat hearts. We also show that the EVs are enriched with cardiac-specific miRNAs known to modulate cardiomyocyte-specific processes. The extended delivery of EVs secreted from iPS-cell-derived cardiomyocytes into the heart may help understand heart recovery and treat heart injury.

The present study demonstrated for the first time that the napkin-ring sign demonstrated on coronary CTA was strongly associated with future ACS events, independent of other high-risk coronary CTA features. Detection of the napkin-ring sign could help identify coronary artery disease patients at high risk of future ACS events.

Arterial stiffness is a significant predictor of cardiovascular disease (CVD), the risk of which is modified by medications for atherosclerotic risk factors and life-style changes. Cardio-ankle vascular index (CAVI) provides noninvasive, objective information on arterial stiffness, independent of blood pressure. This study aimed to investigate changes in CAVI after management of atherosclerotic risk factors, and the impact of these changes on future CVD outcomes in patients with coronary artery disease (CAD). The study consisted of 211 CAD patients (65 ± 10 years, 118 men) with impaired CAVI. CAVI examination was repeated 6 months later. Impaired CAVI was defined as greater than the mean plus 1 s.d. of the age- and gender-specific normal CAVI values, according to results obtained in 5188 healthy subjects. All patients were followed for > 1 year or until the occurrence of a CVD event. Of the 211 patients, CAVI improved in 106 (50%) patients after 6 months, but remained high in 105 (50%) patients. During follow-up (2.9 ± 1.0 years), CVD events occurred in 28 (13%) patients. Persistently impaired CAVI was an independent predictor of future CVD events (P = 0.01), independent of baseline CAVI. CVD outcomes were worse in patients with persistently impaired CAVI than in those with improved CAVI (P < 0.001). Among patients with a normalized CAVI after treatment (n = 22) only one suffered a CVD event. This study was the first to demonstrate that persistent impairment of arterial stiffness was an independent risk factor of future CVD events. Serial measurements of CAVI provide important prognostic information regarding patients with CAD in clinical practice.

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Background:In the absence of obstructive coronary narrowing, impaired coronary flow reserve (CFR) represents coronary microvascular dysfunction. Transthoracic Doppler echocardiography (TTDE) allows non-invasive measurement of CFR in the left anterior descending (LAD) artery. This study aimed to assess the prognostic value of TTDEderived CFR (as a marker of microvascular function) in predicting long-term cardiovascular events, acute coronary syndrome (ACS) events, and the development of heart failure (HF). Methods and Results:This study consisted of 272 patients with coronary artery disease not involving obstructive narrowing (≥50%) in the LAD. Patients underwent TTDE examination for CFR measurement in the LAD. During the follow-up period of 4.0±1.9 years, 32 patients (12%) had cardiovascular events. Cox proportional hazard analysis identified lower CFR as an independent risk factor of cardiovascular events (P<0.001), ACS events (P=0.008), and HF development (P=0.003). A CFR less than 2.4 was the best cut-off value for predicting all events (area under the curve=0.82). CFR excellently predicted the development of HF (area under the curve=0.95), but not ACS events (area under the curve=0.67). Conclusions:This TTDE study demonstrated that CFR was a significant and independent determinant of long-term cardiovascular events, ACS events and HF in patients with coronary artery disease. A CFR greater than 2.0 was not suitable to predict a favorable long-term outcome, even in the absence of obstructive coronary narrowing. (Circ J 2012; 76: 1958 - 1964