Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (S.M., L.V., S.G.M., S.N., M.M., O.J.R.).
Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia (L.V.).
Circ Cardiovasc Imaging. 2023 Oct;16(10):e014863. doi: 10.1161/CIRCIMAGING.122.014863. Epub 2023 Oct 17.
Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability.
We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging.
Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21-1.71] versus Q1, 1.64 [1.53-1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18-1.70]; =0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86-1.98] versus Q1, 1.03 [0.81-1.56]; =0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (=0.219; 0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (=-0.20; =0.04) but also strongly associated with myocardial fibrosis (=-0.24; =0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS.
A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression.
严重的主动脉瓣狭窄（AS）与左心室（LV）肥厚和心脏代谢改变有关，有脂肪变性和心肌能量代谢受损的证据。尽管存在这种共同的表型，但在肥厚的程度和进展为心肌纤维化和心力衰竭方面存在无法解释的广泛个体差异。我们试图确定心脏代谢状态是否是这种变异性的基础。
我们招募了 74 名无症状的 AS 患者和 13 名健康志愿者。使用磷谱测量心肌磷酰肌酸与三磷酸腺苷的比值来测量心脏能量代谢。使用质子谱测量心肌脂质含量。通过心血管磁共振电影成像评估心脏功能。
磷酰肌酸/三磷酸腺苷在 LV 壁厚度四分位数（Q2，1.50 [1.21-1.71] 与 Q1，1.64 [1.53-1.94]）中早期且显著降低，随着疾病严重程度的增加而逐渐下降（Q4，1.48 [1.18-1.70]；=0.02）。所有四分位数的心肌甘油三酯含量总体较高，随着房室压力梯度四分位数的增加而显著增加（Q2，1.36 [0.86-1.98] 与 Q1，1.03 [0.81-1.56]；=0.034）。尽管所有 AS 组均有亚临床 LV 功能障碍的证据，应变参数受损，但收缩期纵向应变受损与能量受损程度相关（=0.219；0.03）。磷酰肌酸/三磷酸腺苷不仅是 LV 壁厚度的独立预测因子（=-0.20；=0.04），而且与心肌纤维化强烈相关（=-0.24；=0.03），表明代谢变化在疾病进展中起作用。当按 AS 的临床严重程度分级时，代谢和功能参数显示出相似的结果。
在肥厚的 AS 心脏的整个范围内存在心肌能量不足和脂肪变性的梯度，这些代谢变化先于不可逆的 LV 重构和亚临床功能障碍。因此，心脏代谢可能在疾病进展中发挥重要且潜在的因果作用。
