The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation Therapeutics

Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to recapitulate the benefits of cells and more. As durable azoic entities, exosomes have numerous practical and conceptual advantages over cells. Will cells end up just being used to manufacture exosomes, or will they find lasting value as primary therapeutic agents? Here, a venerable natural process—the generation of honey—serves as an instructive parable. Flowers make nectar, which bees collect and process into honey. Cells make conditioned medium, which laboratory workers collect and process into exosomes. Unlike flowers, honey is durable, compact, and nutritious, but these facts do not negate the value of flowers themselves. The parallels suggest new ways of thinking about next-generation therapeutics.     

Correlation of serum ST2 levels with severity of diastolic dysfunction on echocardiography and findings on cardiac MRI in patients with heart failure with preserved ejection fraction

ObjectiveThe aim of the present study was to find a correlation of serum Suppression of tumorigenicity 2 (ST2) levels with severity of diastolic dysfunction on echocardiography and cardiac magnetic resonance imaging (CMRI) in heart failure with preserved ejection fraction (HFpEF) patients.MethodsFifty patients aged ≥18 years fulfilling diagnostic criteria for HFpEF were included. ST2 levels, 2D echocardiography and CMRI were performed. Left ventricular ejection fraction, E/A, Septal E/E’, left atrial volume index (LAVI), tricuspid regurgitation (TR), assessment of diastolic dysfunction, T1 mapping in milliseconds and late gadolinium enhancement (LGE) in percentage were noted. The primary outcome measure was to study correlation of ST2 levels with severity of diastolic dysfunction, whereas the secondary outcome measures were to study correlation of ST2 levels with native T1 mapping and LGE on CMRI.ResultsST2 levels showed statistically significant and positive correlation with E/E’ (r = 0.837), peak TR velocity (r = 0.373), LAVI (r = 0.74), E/A (r = 0.420), and T1 values in milliseconds (r = 0.619). There was no statistically significant correlation between ST2 level and LGE in % (r = 0.145). The median ST2 levels in patients with E/E’ > 14 and E/E’ ≤ 14 were 110.8 and 36.1 respectively (p-value < 0.05). The mean ST2 levels were significantly higher in patients who had diastolic dysfunction grade III (126.4) and New York Heart Association class IV (133.3).ConclusionsEvaluation of ST2 adds important information to support the diagnosis of left ventricular diastolic dysfunction in patients with HFpEF.     

How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre‐test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non‐cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), LV filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F₁: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F₂: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.     

射血分数保留心力衰竭与2型糖尿病的研究进展

随着人口老龄化及动脉粥样硬化性心血管疾病（arteriosclerotic cardiovascular disease,ASCVD）发病率的提高,心力衰竭的患病率逐年增加。射血分数保留心力衰竭（heart failure preserved ejection fraction,HFpEF）是其中重要的分型,而2型糖尿病（type 2 diabetes mellitus,T2DM）是导致HFpEF的重要病因之一。本综述通过回顾临床指南和临床研究中HFpEF的诊断要点,从人口学特征、心血管病预后和全因死亡率等不同角度,对比大型流行病学研究中HFpEF与射血分数受损心力衰竭（heart failure reduced ejection fraction,HFrEF）的差异;同时,全面描述并分析HFpEF合并T2DM的临床特征、流行病学表现、发病机制及预后表现。