Dodos Fotiní, Halbsguth Teresa, Erdmann Erland, Hoppe Uta C
Department of Internal Medicine III, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Clin Res Cardiol. 2008 May;97(5):318-26. doi: 10.1007/s00392-007-0633-6. Epub 2008 Jan 14.
Anthracycline therapy is limited by cardiotoxicity. Currently no diagnostic parameter is available allowing ubiquitous and reliable detection of preclinical anthracycline cardiomyopathy and prediction of prognosis.
In 100 consecutive patients receiving anthracycline-based chemotherapy serial measurements of left ventricular systolic and diastolic function, Tei index (a Doppler echocardiographic parameter of global ventricular function), cardiac troponin T (cTnT) and NT-probrain natriuretic peptides (BNP) at baseline and during 1-year follow-up were performed.
Mean ejection fraction (LVEF) significantly decreased immediately after completion of anthracycline therapy (mean dose 226.1 +/- 8.3 mg/m(2)) und further declined during follow-up (65.9 +/- 0.6% Vs. 61.6 +/- 0.7%; P < 0.001), while mean E/A ratio decreased after 6 months (P = 0.05). No patient presented with cardiac symptoms. The Tei index increased after therapy in the majority of patients (78.8%) compared with pre-therapy values indicating myocardial alteration in more patients than previously recognized. cTnT levels did not exceed the upper limit of the normal range in any patient. Seven patients had low-level elevations of cTnT. Only one of these patients developed a concomitant decrease in LVEF. Mean N-terminal-pro-BNP (NT-proBNP) levels did not significantly change after anthracycline administration. However, in 13 patients (15.3%) a marked, transient increase of NT-proBNP was obtained after the first anthracycline cycle without cardiac dysfunction presumably due to altered cardiac loading conditions during chemotherapy.
Low to moderate doses of anthracyclines resulted in subclinical myocardial alteration in more patients than so far noticed. Clinical implications of increased Tei index remain to be determined in long-term. Our results do not support that assessment of cTnT or BNP levels may safely replace serial echocardiographic evaluation of systolic and diastolic function for the monitoring of anthracycline cardiotoxicity.
蒽环类药物治疗受心脏毒性限制。目前尚无诊断参数可实现对临床前蒽环类药物性心肌病的普遍且可靠检测以及预后预测。
对100例连续接受蒽环类药物化疗的患者在基线及1年随访期间进行左心室收缩和舒张功能、Tei指数（一种反映整体心室功能的多普勒超声心动图参数）、心肌肌钙蛋白T（cTnT）和N末端脑钠肽前体（BNP）的系列测量。
蒽环类药物治疗结束后（平均剂量226.1±8.3mg/m²），平均射血分数（LVEF）立即显著下降，且在随访期间进一步降低（65.9±0.6%对61.6±0.7%；P<0.001），而平均E/A比值在6个月后降低（P=0.05）。无患者出现心脏症状。与治疗前相比，大多数患者（78.8%）治疗后Tei指数升高，表明心肌改变的患者比之前认识到的更多。任何患者的cTnT水平均未超过正常范围上限。7例患者cTnT有低水平升高。其中仅1例患者同时出现LVEF下降。蒽环类药物给药后平均N末端脑钠肽前体（NT-proBNP）水平无显著变化。然而，13例患者（15.3%）在首个蒽环类药物疗程后出现NT-proBNP明显短暂升高，且无心脏功能障碍，推测是由于化疗期间心脏负荷状况改变所致。
低至中等剂量的蒽环类药物导致亚临床心肌改变的患者比迄今所注意到的更多。Tei指数升高的临床意义仍有待长期确定。我们的结果不支持cTnT或BNP水平评估可安全替代对收缩和舒张功能进行系列超声心动图评估以监测蒽环类药物心脏毒性。
