Maredziak Monika, Bengs Susan, Portmann Angela, Haider Achi, Wijnen Winandus J, Warnock Geoffrey I, Etter Dominik, Froehlich Sandro, Fiechter Michael, Meisel Alexander, Treyer Valerie, Fuchs Tobias A, Pazhenkottil Aju P, Buechel Ronny R, Kaufmann Philipp A, Gebhard Catherine
Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3094-3106. doi: 10.1007/s00259-020-04892-x. Epub 2020 Jun 6.
Recently, a new disease phenotype characterized by supra-normal left ventricular ejection fraction (snLVEF) has been suggested, based on large datasets demonstrating an increased all-cause mortality in individuals with an LVEF > 65%. The underlying mechanisms of this association are currently unknown.
A total of 1367 patients (352 women, mean age 63.1 ± 11.6 years) underwent clinically indicated rest/adenosine stress ECG-gated N-ammonia positron emission tomography (PET) between 1995 and 2017 at our institution. All patients were categorized according to LVEF. A subcohort of 698 patients (150 women) were followed for major adverse cardiac events (MACEs), a composite of cardiac death, non-fatal myocardial infarction, cardiac-related hospitalization, and revascularization.
The prevalence of a snLVEF (≥ 65%) was higher in women as compared to that in men (31.3% vs 18.8%, p < 0.001). In women, a significant reduction in coronary flow reserve (CFR, p < 0.001 vs normal LVEF) and a blunted heart rate reserve (% HRR, p = 0.004 vs normal LVEF) during pharmacological stress testing-a surrogate marker for autonomic dysregulation-were associated with snLVEF. Accordingly, reduced CFR and HRR were identified as strong and independent predictors for snLVEF in women in a fully adjusted multinomial regression analysis. After a median follow-up time of 5.6 years, women with snLVEF experienced more often a MACE than women with normal (55-65%) LVEF (log rank p < 0.001), while such correlation was absent in men (log rank p = 0.76).
snLVEF is associated with an increased risk of MACE in women, but not in men. Microvascular dysfunction and an increased sympathetic tone in women may account for this association.
最近，基于大型数据集显示左心室射血分数（LVEF）>65%的个体全因死亡率增加，有人提出了一种以超正常左心室射血分数（snLVEF）为特征的新疾病表型。这种关联的潜在机制目前尚不清楚。
1995年至2017年期间，共有1367例患者（352例女性，平均年龄63.1±11.6岁）在我们机构接受了临床指示的静息/腺苷负荷心电图门控N-氨正电子发射断层扫描（PET）。所有患者均根据LVEF进行分类。对698例患者（150例女性）的亚组进行主要不良心脏事件（MACE）随访，MACE是心脏死亡、非致命性心肌梗死、心脏相关住院和血运重建的综合指标。
女性snLVEF（≥65%）的患病率高于男性（31.3%对18.8%，p<0.001）。在女性中，药物负荷试验期间冠状动脉血流储备（CFR，与正常LVEF相比p<0.001）显著降低，心率储备（%HRR，与正常LVEF相比p=0.004）钝化，这是自主神经调节异常的替代指标，与snLVEF相关。因此，在完全调整的多项回归分析中，CFR和HRR降低被确定为女性snLVEF的强独立预测因素。中位随访时间为5.6年后，snLVEF的女性比正常LVEF（55-65%）的女性更常发生MACE（对数秩检验p<0.001），而男性中不存在这种相关性（对数秩检验p=0.76）。
snLVEF与女性发生MACE的风险增加相关，但与男性无关。女性的微血管功能障碍和交感神经张力增加可能解释了这种关联。
