The Ohio State University, Columbus, OH 43210, USA.
Eur Heart J. 2011 Mar;32(5):561-7. doi: 10.1093/eurheartj/ehq443. Epub 2010 Dec 14.
Cardiomyopathy produces significant mortality in patients with Friedreich ataxia (FA), a genetic disorder that produces intra-mitochondrial iron accumulation. We sought to test the hypothesis that abnormal myocardial perfusion reserve and fibrosis represent early manifestations of cardiomyopathy.
Twenty-six patients with genetically proven FA ages 36 ± 12 years without cardiomyopathy and eight controls underwent cardiac magnetic resonance with adenosine. Precontrast imaging for myocardial iron estimation was performed. Myocardial perfusion reserve index (MPRI) was quantified using the normalized upslope of myocardial enhancement during vasodilator stress vs. rest. Left ventricular (LV) mass and volumes were computed from short-axis cine images. Serologies included lipids, and platelets were isolated for iron quantification using inductively coupled plasma mass spectrometry. Left ventricular ejection fraction and mass averaged 64.1 ± 8.3% and 62.7 ± 16.7 g/m², respectively, indicating preserved systolic function and absence of significant hypertrophy. Myocardial perfusion reserve index quantification revealed significantly lower endocardial-to-epicardial perfusion reserve in patients vs. controls (0.80 ± 0.18 vs. 1.22 ± 0.36, P = 0.01). Lower MPRI was predicted by increased number of metabolic syndrome (met-S) features (P < 0.01). Worse concentric remodelling occurred with increased GAA repeat length (r = 0.64, P < 0.001). Peripheral platelet iron measurement showed no distinction between patients and controls (5.4 ± 8.5 × 10⁻⁷ vs. 5.5 ± 2.9 × 10⁻⁷ ng/platelet, P = 0.88), nor did myocardial T2* measures.
Patients with FA have abnormal myocardial perfusion reserve that parallels met-S severity. Impaired perfusion reserve and fibrosis occur in the absence of significant hypertrophy and prior to clinical heart failure, providing potential therapeutic targets for stage B cardiomyopathy in FA and related myocardial diseases.
弗里德赖希共济失调（FA）是一种遗传性疾病，会导致线粒体内部铁积累，从而导致患者出现心肌病变并导致较高的死亡率。我们试图验证一个假设，即异常的心肌灌注储备和纤维化是心肌病的早期表现。
26 名年龄在 36±12 岁且无心肌病的遗传性 FA 患者和 8 名对照者接受了腺苷心脏磁共振检查。进行心肌铁定量的预对比成像。通过血管扩张剂刺激与休息期间心肌增强的归一化上升斜率来量化心肌灌注储备指数（MPRI）。从短轴电影图像计算左心室（LV）质量和容量。血清学包括脂质，使用电感耦合等离子体质谱法分离血小板以进行铁定量。左心室射血分数和质量分别为 64.1±8.3%和 62.7±16.7 g/m²，表明收缩功能正常且不存在明显的肥大。与对照组相比，患者的心肌内-心外膜灌注储备指数明显较低（0.80±0.18 与 1.22±0.36，P=0.01）。MPRI 降低与代谢综合征（met-S）特征数量增加相关（P<0.01）。GAA 重复长度增加与更严重的向心性重塑相关（r=0.64，P<0.001）。患者与对照组之间的外周血小板铁测量没有区别（5.4±8.5×10⁻⁷与 5.5±2.9×10⁻⁷ ng/血小板，P=0.88），心肌 T2* 测量也没有区别。
FA 患者存在异常的心肌灌注储备，与 met-S 严重程度平行。在没有明显肥大和临床心力衰竭之前，就已经出现了灌注储备受损和纤维化，这为 FA 和相关心肌疾病的 B 期心肌病提供了潜在的治疗靶点。
