Kaye D M, Lefkovits J, Jennings G L, Bergin P, Broughton A, Esler M D
Alfred and Baker Medical Unit, Baker Medical Research Institute, Alfred Hospital, Melbourne, Australia.
J Am Coll Cardiol. 1995 Nov 1;26(5):1257-63. doi: 10.1016/0735-1097(95)00332-0.
In view of previous experimental evidence relating sympathetic nervous overactivity in the heart to myocardial necrosis and ventricular arrhythmias, we prospectively examined the hypothesis that heightened cardiac sympathetic nervous activity is associated with an adverse outcome in patients with moderate to severe heart failure.
Despite recent therapeutic advances, patients with heart failure continue to have high mortality from progressive hemodynamic decompensation and lethal ventricular arrhythmias. It is believed that initially compensatory increases in sympathetic nervous system activity may ultimately be maladaptive, potentially contributing to subsequent adverse events.
Sixty patients with moderate to severe heart failure (left ventricular ejection fraction 18.9 +/- 0.9% [mean +/- SE]) were studied prospectively. In addition to the compilation of a hemodynamic, biochemical and electrocardiographic profile for each patient, whole-body and cardiac sympathetic activity were determined by isotope dilution. The relation of these variables to outcome was determined by Cox proportional hazards analysis.
The mean follow-up period of the study group was 7 +/- 1 months (range 1 to 24) with a 12-month actuarial survival of 75%. Deaths (14 in all) were accounted for either by sudden death or progressive heart failure in equal numbers. The rate of release of norepinephrine from the heart was significantly higher in patients with heart failure than in healthy subjects (402 +/- 37 vs. 105 +/- 19 pmol/min, p < 0.01), although the values for heart failure ranged widely from normal to 10 times normal. By univariate Cox proportional hazards analysis, pulmonary capillary wedge pressure (p < 0.01), mean pulmonary artery pressure (p < 0.001), serum sodium levels (p < 0.01) and cardiac norepinephrine spill-over rate (p < 0.001) were identified as significant prognostic markers. In a multivariate analysis, cardiac norepinephrine spillover rate was identified as the most powerful prognostic marker (p = 0.0006) of those evaluated in this study.
These results suggest that activation of the sympathetic nervous system in patients with heart failure, specifically the cardiac sympathetic nerves, may contribute to the poor prognosis associated with severe heart failure. The data therefore provide a rationale for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure.
鉴于先前有关心脏交感神经活动过度与心肌坏死及室性心律失常相关的实验证据，我们前瞻性地检验了这一假说，即心脏交感神经活动增强与中重度心力衰竭患者的不良预后相关。
尽管近期治疗取得进展，但心力衰竭患者仍因进行性血流动力学失代偿和致命性室性心律失常而有较高死亡率。据信，交感神经系统活动最初的代偿性增加最终可能是适应不良的，可能导致随后的不良事件。
对60例中重度心力衰竭患者（左心室射血分数为18.9±0.9%[均值±标准误]）进行前瞻性研究。除了为每位患者编制血流动力学、生化和心电图资料外，通过同位素稀释法测定全身和心脏交感神经活动。通过Cox比例风险分析确定这些变量与预后的关系。
研究组的平均随访期为7±1个月（范围1至24个月），12个月的精算生存率为75%。死亡病例（共14例）中，猝死和进行性心力衰竭各占一半。心力衰竭患者心脏去甲肾上腺素的释放速率显著高于健康受试者（402±37对105±19 pmol/分钟，p<0.01），尽管心力衰竭患者的值范围很广，从正常到正常的10倍。通过单变量Cox比例风险分析，肺毛细血管楔压（p<0.01）、平均肺动脉压（p<0.001）、血清钠水平（p<0.01）和心脏去甲肾上腺素溢出率（p<0.001）被确定为显著的预后标志物。在多变量分析中，心脏去甲肾上腺素溢出率被确定为本研究评估的最有力的预后标志物（p = 0.0006）。
这些结果表明，心力衰竭患者交感神经系统的激活，特别是心脏交感神经，可能导致与严重心力衰竭相关的不良预后。因此，这些数据为在心力衰竭患者管理中使用β-肾上腺素能阻滞剂等药物提供了理论依据。
