Hohnloser Stefan H, Ikeda Takanori, Cohen Richard J
Division of Cardiology, Department of Medicine, J W Goethe University, Frankfurt, Germany.
Heart Rhythm. 2009 Mar;6(3 Suppl):S36-44. doi: 10.1016/j.hrthm.2008.10.011. Epub 2008 Oct 11.
Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well.
This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs.
This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (< or =15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group).
In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD.
This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD.
在许多研究中，微伏级T波交替（MTWA）检测已被证明是心脏性猝死（SCD）危险因素患者发生室性快速心律失常事件（VTE）的高度准确预测指标，但这些患者既往无持续性VTE病史（一级预防患者）。在最近一些涉及预防性植入心脏复律除颤器（ICD）的一级预防患者的研究中，MTWA的表现并不理想。
本研究检验了以下假设，即MTWA是未植入ICD的一级预防患者发生VTE的准确预测指标，但对于已植入ICD的此类患者，并非合适的ICD治疗预测指标。
本研究确定了在一级预防人群中评估采用频谱分析方法测量MTWA的前瞻性临床试验，并分析了以下研究：（1）植入ICD的患者很少，因此报告的终点VTE中无或仅有一小部分（≤15%）是合适的ICD治疗（低ICD组），或（2）许多患者植入了ICD，且报告的终点VTE中大多数是合适的ICD治疗（高ICD组）。
在包含3682例患者的低ICD组中，MTWA检测结果为非阴性与阴性相比的风险比为13.6（95%置信区间[CI]8.5至30.4），MTWA检测结果为阴性的患者年事件发生率为0.3%（95%CI：0.1%至0.5%）。相比之下，在包含2234例患者的高ICD组中，风险比仅为1.6（95%CI：1.2至2.1），MTWA检测结果为阴性的患者年事件发生率升至5.4%（95%CI：4.1%至6.7%）。为支持这些发现，我们分析了多中心自动除颤器试验II（MADIT II）和心力衰竭试验中的心脏性猝死（SCD-HeFT）试验的已发表数据，并确定在那些试验中，仅32%接受合适ICD治疗的患者避免了SCD。
本研究发现，采用频谱分析方法的MTWA检测为预测未植入ICD的一级预防患者发生VTE提供了一种准确方法；特别是，MTWA检测结果为阴性的此类患者事件发生率非常低。在ICD治疗的前瞻性试验中，接受合适ICD治疗的患者数量大大超过因ICD治疗而避免SCD的患者数量。在涉及植入ICD患者的试验中，这些多余的合适ICD治疗似乎在MTWA检测结果为阴性和非阴性的患者之间随机分布，从而掩盖了MTWA对SCD的预测准确性。合适的ICD治疗是SCD不可靠的替代终点。
