Plasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction: Data From the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Study.
Plasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction: Data From the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Study.
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DOI：
10.1161/circheartfailure.115.002551
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators
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作者：
Zile MR;Jhund PS;Baicu CF;Claggett BL;Pieske B;Voors AA;Prescott MF;Shi V;Lefkowitz M;McMurray JJ;Solomon SD;Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators
保留射血分数的心力衰竭是一种与细胞外基质改变有关的临床综合征。本研究的目的是确定纤维化生物标志物是否准确反映了保留射血分数的心力衰竭患者疾病的存在和严重程度以及潜在的病理生理学，并改变对治疗的反应。在缬沙坦或LCZ696随机分组后基线、12周和36周，ARNI与ARB在保留射血分数（PARAMOUNT）治疗心力衰竭的前瞻性比较中，测量了四种生物标志物，可溶性ST2（一种白细胞介素-1受体家族成员）、半凝集素-3、基质金属蛋白酶-2和胶原ⅲn端前肽。我们检查了基线生物标志物、人口统计学和超声心动图特征、主要终点（n端前b型利钠肽变化）和次要终点（左心房容积变化）之间的关系。与之前发表的对照相比，可溶性ST2 （33 [24.6-48.1] ng/mL）和凝集素3 （17.8 [14.1-22.8]ng/mL）的中位数（四分位数范围）更高，基质金属蛋白酶-2 （188 [155.5-230.6]ng/mL）更低；III型胶原n端前肽（5.6 [4.3-6.9]ng/mL）与对照值相似。所有4项生物标志物均与疾病严重程度相关，如n端前b型利钠肽、E/E′和左心房容积。基线生物标志物没有改变LCZ696降低n端前b型利钠肽的反应；然而，左房容积减少随ST2和凝集素3可溶性形式的基线水平而变化；小于观察到的中位数（<33 ng/mL可溶性ST2和<17.8 ng/mL凝集素3）的患者左房容积减小，高于中位数的患者则没有。虽然LCZ696降低了n端前b型利钠肽，但其他4种生物标志物的水平不受时间的影响。在保留射血分数的心力衰竭患者中，反映胶原稳态的生物标志物与疾病的存在和严重程度以及潜在的病理生理相关，并可能改变对治疗的结构反应。
Heart failure with preserved ejection fraction is a clinical syndrome that has been associated with changes in the extracellular matrix. The purpose of this study was to determine whether profibrotic biomarkers accurately reflect the presence and severity of disease and underlying pathophysiology and modify response to therapy in patients with heart failure with preserved ejection fraction. Four biomarkers, soluble form of ST2 (an interleukin-1 receptor family member), galectin-3, matrix metalloproteinase-2, and collagen III N-terminal propeptide were measured in the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) trial at baseline, 12 and 36 weeks after randomization to valsartan or LCZ696. We examined the relationship between baseline biomarkers, demographic and echocardiographic characteristics, change in primary (change in N-terminal pro B-type natriuretic peptide) and secondary (change in left atrial volume) end points. The median (interquartile range) value for soluble form of ST2 (33 [24.6–48.1] ng/mL) and galectin 3 (17.8 [14.1–22.8] ng/mL) were higher, and for matrix metalloproteinase-2 (188 [155.5–230.6] ng/mL) lower, than in previously published referent controls; collagen III N-terminal propeptide (5.6 [4.3–6.9] ng/mL) was similar to referent control values. All 4 biomarkers correlated with severity of disease as indicated by N-terminal pro B-type natriuretic peptide, E/E′, and left atrial volume. Baseline biomarkers did not modify the response to LCZ696 for lowering N-terminal pro B-type natriuretic peptide; however, left atrial volume reduction varied by baseline level of soluble form of ST2 and galectin 3; patients with values less than the observed median (<33 ng/mL soluble form of ST2 and <17.8 ng/mL galectin 3) had reduction in left atrial volume, those above median did not. Although LCZ696 reduced N-terminal pro B-type natriuretic peptide, levels of the other 4 biomarkers were not affected over time. In patients with heart failure with preserved ejection fraction, biomarkers that reflect collagen homeostasis correlated with the presence and severity of disease and underlying pathophysiology, and may modify the structural response to treatment.