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Hypertension often leads to cardiovascular disease and kidney dysfunction. Exosomes secreted from cardiosphere-derived cells (CDC-exo) and their most abundant small RNA constituent, the Y RNA fragment EV-YF1, exert therapeutic benefits after myocardial infarction. Here, we investigated the effects of CDC-exo and EV-YF1, each administered individually, in a model of cardiac hypertrophy and kidney injury induced by chronic infusion of Ang (angiotensin) II. After 2 weeks of Ang II, multiple doses of CDC-exo or EV-YF1 were administered retro-orbitally. Ang II infusion induced an elevation in systolic blood pressure that was not affected by CDC-exo or EV-YF1. Echocardiography confirmed that Ang II infusion led to cardiac hypertrophy. CDC-exo and EV-YF1 both attenuated cardiac hypertrophy and reduced cardiac inflammation and fibrosis. In addition, both CDC-exo and EV-YF1 improved kidney function and diminished renal inflammation and fibrosis. The beneficial effects of CDC-exo and EV-YF1 were associated with changes in the expression of the anti-inflammatory cytokine IL (interleukin)-10 in plasma, heart, spleen, and kidney. In summary, infusions of CDC-exo or EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion, without affecting blood pressure, in association with altered IL-10 expression. Exosomes and their defined noncoding RNA contents may represent potential new therapeutic approaches for hypertension-associated cardiovascular and renal damage. [ABSTRACT FROM AUTHOR]

For >4 decades, the holy grail in the treatment of acute myocardial infarction has been the mitigation of lethal injury. Despite promising initial results and decades of investigation by the cardiology research community, the only treatment with proven efficacy is early reperfusion of the occluded coronary artery. The remarkable record of failure has led us and others to wonder if cardioprotection is dead. The path to translation, like the ascent to Everest, is certainly littered with corpses. We do, however, highlight a therapeutic principle that provides a glimmer of hope: cellular postconditioning. Administration of cardiosphere-derived cells after reperfusion limits infarct size measured acutely, while providing long-term structural and functional benefits. The recognition that cell therapy may be cardioprotective, and not just regenerative, merits further exploration before we abandon the pursuit entirely. [ABSTRACT FROM AUTHOR]

Background: Myocardial scarring from infarction or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS score has been extensively validated for estimating myocardial infarction scar size in the absence of ECG confounders, but has not been tested to quantify scar in patients with hypertrophy, bundle branch/fascicular blocks, or nonischemic cardiomyopathy. We assessed the hypotheses that (1) QRS scores (modified for each ECG confounder) correctly identify and quantify scar in ischemic and nonischemic patients when compared with the reference standard of cardiac magnetic resonance using late-gadolinium enhancement, and (2) QRS-estimated scar size predicts inducible sustained monomorphic ventricular tachycardia during electrophysiological testing.Methods and Results: One hundred sixty-two patients with left ventricular ejection fraction < or =35% (95 ischemic, 67 nonischemic) received 12-lead ECG and cardiac magnetic resonance using late-gadolinium enhancement before implantable cardioverter defibrillator placement for primary prevention of sudden cardiac death. QRS scores correctly diagnosed cardiovascular magnetic resonance scar presence with receiver operating characteristics area under the curve of 0.91 and correlation for scar quantification of r=0.74 (P<0.0001) for all patients. Performance within hypertrophy, conduction defect, and nonischemic subgroups ranged from area under the curve of 0.81 to 0.94 and r=0.60 to 0.80 (P<0.001 for all). Among the 137 patients undergoing electrophysiological or device testing, each 3-point QRS-score increase (9% left ventricular scarring) was associated with an odds ratio for inducing monomorphic ventricular tachycardia of 2.2 (95% CI, 1.5 to 3.2; P<0.001) for all patients, 1.7 (1.0 to 2.7, P=0.04) for ischemics, and 2.2 (1.0 to 5.0, P=0.05) for nonischemics.Conclusions: QRS scores identify and quantify scar in ischemic and nonischemic cardiomyopathy patients despite ECG confounders. Higher QRS-estimated scar size is associated with increased arrhythmogenesis and warrants further study as a risk-stratifying tool. [ABSTRACT FROM AUTHOR]

Background—Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. Methods and Results—Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI. Histology was used to assess iron deposition and to examine relationships between iron content with macrophage infiltration, proinflammatory cytokine synthesis, and matrix metalloproteinase activation. Atomic resolution transmission electron microscopy was used to determine iron crystallinity, and energydispersive X-ray spectroscopy was used to identify the chemical composition of the iron composite. PMO with or without reperfusion hemorrhage led to chronic iron deposition, and the extent of this deposition was strongly related to PMO volume (r>0.8). Iron deposits were found within macrophages as aggregates of nanocrystals (≈2.5 nm diameter) in the ferric state. Extent of iron deposits was strongly correlated with proinflammatory burden, collagen-degrading enzyme activity, infarct resorption, and adverse structural remodeling (r>0.5). Conclusions—Crystallized iron deposition from PMO is directly related to proinflammatory burden, infarct resorption, and adverse left ventricular remodeling in the chronic phase of MI in canines. Therapeutic strategies to combat adverse remodeling could potentially benefit from taking into account the chronic iron-driven inflammatory process. [ABSTRACT FROM AUTHOR]

Late-gadolinium-enhanced (LGE) cardiac MRI (CMR) is a powerful method for characterizing myocardial infarction (MI), but the requisite gadolinium infusion is estimated to be contraindicated in ≈20% of patients with MI because of end-stage chronic kidney disease. The purpose of this study is to investigate whether T1 CMR obtained without contrast agents at 3 T could be an alternative to LGE CMR for characterizing chronic MIs using a canine model of MI.Canines (n=29) underwent CMR at 7 days (acute MI [AMI]) and 4 months (chronic MI [CMI]) after MI. Infarct location, size, and transmurality measured by using native T1 maps and LGE images at 1.5 T and 3 T were compared. Resolution of edema between AMI and CMI was examined with T2 maps. T1 maps overestimated infarct size and transmurality relative to LGE images in AMI (P=0.016 and P=0.007, respectively), which was not observed in CMI (P=0.49 and P=0.81, respectively) at 3 T. T1 maps underestimated infarct size and transmurality relative to LGE images in AMI and CMI (P<0.001) at 1.5 T. Relative to the remote territories, T1 of the infarcted myocardium was increased in CMI and AMI (P<0.05), and T2 of the infarcted myocardium was increased in AMI (P<0.001) but not in CMI (P>0.20) at both field strengths. Histology showed extensive replacement fibrosis within the CMI territories. CMI detection sensitivity and specificity of T1 CMR at 3 T were 95% and 97%, respectively.Native T1 maps at 3 T can determine the location, size, and transmurality of CMI with high diagnostic accuracy. Patient studies are necessary for clinical translation. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the link between myocardial tissue heterogeneity through the cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) and cardiac arrhythmic outcome. It claims that heart failure (HF) linked with ischemic and nonischemic cardiomyopathy is characterized by systemic inflammation. The study was authorized by the Johns Hopkins Hospital Institutional Review Board.

The article presents a study on the use of cardiosphere-derived cells (CDCs) labeled with superparamagnetic microspheres (SPMs) for retention of transplanted cells in the heart. It is reported that cells were attracted towards the magnet and accumulated around the ischemic zone with magnetic targeting. It concludes that cell retention, engraftment and functional benefit are enhanced with magnetic targeting.

The article examines the paracrine effects in cultured as cardiospheres (CSps) or CSp-derived cell (CDC) transplantation and their significance versus direct differentiation for transplanted cell survival in mice. It notes that transplanted CDCs serve as role models, recruiting endogenous regeneration and improves tissue resistance to ischemic stress. It points out that the role model effect exceeds the direct regeneration.

The article offers information on the biological therapies for cardiac arrhythmias. It mentions that arrhythmias are among the cardiac rhythm disorders mostly due to failures of impulse generation and conduction. It says that present therapies for arrhythmias rely on pharmacology, ablation or electronic devices but with varying degree of success. It presents several gene- and cell-based therapies for tachyarrhythmia and biological pacemaker for curing bradyarrhythmia.

The article reviews the study which examines the myocardial regeneration of stem and progenitor cell transplantation into the heart. Accordingly, engraftment and low cell retention would limit the successful application of cell therapy. However, engraftment can be improved by using accurate methods of tracking cells and focusing to quantify cell survival.

The article presents a study on the reentry dynamics and role of individual ion channels on reentry in vitro models of the healed infarct border zone (IBZ). The researcher developed the healed IBZ in vitro models by coculturing skeletal myotubes with ventricular myocytes of neonatal rat. It adds that they utilized optical mapping at high temporal and spatial resolution to assess the impact of Na +, Ca2+, and K+ channel blockers on reentrant arrhythmia dynamics.

The author reminisces his editorship for "Circulation Research" from 1999-2009. He realized that he is part of the venerable publication about cardiovascular science and contributed to its success in maintaining its reputation. Results of the analysis of the competitiveness and social acceptance rate show its significant increase every year which signifies its reliability in providing information related to cardiovascular science.

The article discusses the role of IK1 heterogeneity and level in the genesis and stability of spiral waves and the potential importance of IK1 as an antiarrhythmia target. An overexpression of neonatal rat ventricular myocytes (NRVMs) increased IK1 density and hyperpolarized resting membrane potential and increased action potential upstroke velocity compared with green fluorescent protein-transduced NRVMs.