Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death.
Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death.
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DOI：
10.1161/jaha.123.029542
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发表时间：
2023-07-04
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
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在小鼠和小患者亚组中的研究表明，主动脉瓣狭窄的心脏重塑中存在代谢功能障碍，但目前还没有对主动脉瓣狭窄的人体代谢进行长期随访和表征的大型综合研究。在一项多中心前瞻性队列研究中，我们使用主成分分析总结了519例受试者经导管主动脉瓣植入术前左心室结构和功能的12项超声心动图指标（推导）。我们在221种代谢物中使用最小绝对收缩和选择算子回归来定义每种结构模式的代谢特征，并在原始队列和多达2个验证队列中测量它们与死亡和多死亡的关系（N=543用于总体验证）。在推导队列中（519名个体;中位年龄84岁，45%为女性，95%为白色个体），我们确定了左心室重构的3个轴，广泛地指定收缩功能，舒张功能和腔室容积。每个轴的代谢物特征指定了肥大和心功能不全的已知和新途径。在中位数为3.1年（205例死亡）的研究中，舒张功能代谢物评分与经导管主动脉瓣植入术后死亡独立相关（评分每增加1个标准差，校正风险比为1.54 [95%CI，1.25-1.90]; P<0.001），每个验证队列的影响相似。舒张功能的代谢物评分同时与多项指标相关，提示主动脉瓣狭窄患者的心源性和非心源性状态之间存在代谢联系。心脏结构的代谢产物谱可识别经导管主动脉瓣植入术和并发多发性硬化后死亡的高风险个体。这些结果要求努力解决与风险相关的潜在可逆代谢生物学，以优化经导管主动脉瓣植入后的恢复、康复和生存。
Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long‐term follow‐up and characterization currently exist. Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre–transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post–transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25–1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post–transcatheter aortic valve implantation recovery, rehabilitation, and survival.
DOI：
10.1007/s00392-020-01754-2
发表时间：
2021-03
期刊：
Clinical research in cardiology : official journal of the German Cardiac Society
影响因子：
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作者：
Haase D;Bäz L;Bekfani T;Neugebauer S;Kiehntopf M;Möbius-Winkler S;Franz M;Schulze PC
通讯作者：
Schulze PC