Dong Ying-Xue, Burnett John C, Chen Horng H, Sandberg Sharon, Yang Yan-Zhong, Zhang Yanhua, Chen Peng-Sheng, Cha Yong-Mei
Division of Cardiovascular Diseases, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
J Interv Card Electrophysiol. 2011 Apr;30(3):241-9. doi: 10.1007/s10840-011-9551-7. Epub 2011 Feb 19.
Neurohormonal dysregulation contributes to heart failure (HF) progression. We sought to determine the effect of cardiac resynchronization therapy (CRT) on nerve growth factor (NGF), a biomarker that promotes the maturation and survival of sympathetic nerve endings, and amino-terminal propeptide of type III procollagen (PIIINP), a marker of type III collagen synthesis.
This prospective study consisted of 45 consecutive patients who received cardiac resynchronization therapy defibrillator for advanced HF and 20 healthy age-matched controls. New York Heart Association class, distance of 6-min walk, echocardiography and plasma concentrations of NGF, PIIINP, b-type natriuretic peptide (BNP), norepinephrine, and epinephrine were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume index at 6-month follow-up.
The baseline BNP (2.61 ± 0.51 vs. 1.53 ± 0.44 ug/L, P < 0.01) and PIIINP (0.88 ± 0.21 vs. 0.71 ± 0.14 μg/L, P = 0.01), but not other biomarkers, were elevated in HF compared to controls. Twenty-two of 45 patients (49%) responded to CRT. The responder group demonstrated significant decrease only in BNP level from 2.61 ± 0.51 to 2.31 ± 0.41 μg/L (P = 0.04) at 6-month follow-up, paralleling the clinical improvements. The baseline PIIINP, rather than the other biomarkers, was lower in CRT responders than non-responders (0.80 ± 0.20 vs. 0.96 ± 0.19 μg/L, P = 0.03). Univariate and multivariate analysis showed that less elevated plasma PIIINP level in HF might be an independent biomarker predicting better response to CRT (odds ratio = 0.20, 95% CI = 0.03-1.17, P = 0.07).
The less elevated PIIINP level in HF, which is suggestive of a lesser amount of cardiac fibrosis, has a trend in association with a favorable response to CRT. Contrary to previous reports, NGF levels are not reduced during HF with optimal medical therapy, and there is no NGF rebound in CRT responders.
神经激素失调促进心力衰竭（HF）进展。我们试图确定心脏再同步治疗（CRT）对神经生长因子（NGF）和III型前胶原氨基端前肽（PIIINP）的影响，NGF是促进交感神经末梢成熟和存活的生物标志物，PIIINP是III型胶原合成的标志物。
这项前瞻性研究包括45例连续接受心脏再同步治疗除颤器治疗晚期HF的患者和20例年龄匹配的健康对照者。在CRT治疗前和治疗6个月后，测量纽约心脏协会分级、6分钟步行距离、超声心动图以及血浆NGF、PIIINP、B型利钠肽（BNP）、去甲肾上腺素和肾上腺素的浓度。CRT反应定义为在6个月随访时左心室收缩末期容积指数降低15%或更多。
与对照组相比，HF患者的基线BNP（2.61±0.51 vs. 1.53±0.44μg/L，P<0.01）和PIIINP（0.88±0.21 vs. 0.71±0.14μg/L，P=0.01）升高，但其他生物标志物未升高。45例患者中有22例（49%）对CRT有反应。反应组在6个月随访时仅BNP水平从2.61±0.51显著降至2.31±0.41μg/L（P=0.04），与临床改善情况平行。CRT反应者的基线PIIINP低于无反应者，而不是其他生物标志物（0.80±0.20 vs. 0.96±0.19μg/L，P=0.03）。单因素和多因素分析表明，HF患者血浆PIIINP水平升高较少可能是预测CRT反应较好的独立生物标志物（比值比=0.20，95%可信区间=0.03-1.17，P=0.07）。
HF患者中PIIINP水平升高较少提示心脏纤维化程度较轻，与对CRT的良好反应相关。与先前报道相反，在最佳药物治疗的HF期间，NGF水平未降低，CRT反应者也没有NGF反弹。
