School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
Department of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
JACC Heart Fail. 2015 Mar;3(3):202-11. doi: 10.1016/j.jchf.2014.09.009. Epub 2015 Jan 28.
The aim of this study was to determine whether short-term treatment with perhexiline improves cardiac energetics, left ventricular function, and symptoms of heart failure by altering cardiac substrate utilization.
Perhexiline improves exercise capacity and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). (31)P cardiac magnetic resonance spectroscopy can be used to quantify the myocardial phosphocreatine/adenosine triphosphate ratio. Because improvement of HF syndrome can improve cardiac energetics secondarily, we investigated the effects of short-term perhexiline therapy.
Patients with systolic HF of nonischemic etiology (n = 50, 62 ± 1.8 years of age, New York Heart Association functional class II to IV, LVEF: 27.0 ± 1.44%) were randomized to receive perhexiline 200 mg or placebo for 1 month in a double-blind fashion. Clinical assessment, echocardiography, and (31)P cardiac magnetic resonance spectroscopy were performed at baseline and after 1 month. A substudy of 22 patients also underwent cross-heart blood sampling at completion of the study to quantify metabolite utilization.
Perhexiline therapy was associated with a 30% increase in the phosphocreatine/adenosine triphosphate ratio (from 1.16 ± 0.39 to 1.51 ± 0.51; p < 0.001) versus a 3% decrease with placebo (from 1.36 ± 0.31 to 1.34 ± 0.31; p = 0.37). Perhexiline therapy also led to an improvement in New York Heart Association functional class compared with placebo (p = 0.036). Short-term perhexiline therapy did not change LVEF. Cross-heart measures of cardiac substrate uptake and respiratory exchange ratio (which reflects the ratio of substrates used) did not differ between patients who received perhexiline versus placebo.
Perhexiline improves cardiac energetics and symptom status with no evidence of altered cardiac substrate utilization. No change in LVEF is seen at this early stage. (Metabolic Manipulation in Chronic Heart Failure; NCT00841139).
本研究旨在通过改变心脏底物利用来确定短期应用哌克昔林是否能改善心脏能量代谢、左心室功能和心力衰竭症状。
哌克昔林可提高心力衰竭（HF）患者的运动能力和左心室射血分数（LVEF）。31P 心脏磁共振波谱可用于定量心肌磷酸肌酸/三磷酸腺苷比值。由于 HF 综合征的改善可能会间接改善心脏能量代谢，因此我们研究了短期哌克昔林治疗的效果。
50 例非缺血性病因的收缩性 HF 患者（62 ± 1.8 岁，纽约心脏协会心功能 II 至 IV 级，LVEF：27.0 ± 1.44%）被随机分为哌克昔林 200 mg 或安慰剂组，进行为期 1 个月的双盲治疗。分别于基线和 1 个月后进行临床评估、超声心动图和 31P 心脏磁共振波谱检查。22 例患者的亚组研究也在研究结束时进行了交叉心脏采血，以定量代谢物利用。
与安慰剂相比，哌克昔林治疗可使磷酸肌酸/三磷酸腺苷比值增加 30%（从 1.16 ± 0.39 增加到 1.51 ± 0.51；p<0.001），而安慰剂组则降低 3%（从 1.36 ± 0.31 减少到 1.34 ± 0.31；p=0.37）。与安慰剂相比，哌克昔林治疗还可改善纽约心脏协会心功能分级（p=0.036）。短期哌克昔林治疗未改变 LVEF。与接受哌克昔林的患者相比，接受安慰剂的患者的心脏底物摄取和呼吸交换率（反映底物利用的比值）的交叉心脏测量无差异。
哌克昔林可改善心脏能量代谢和症状，而无心脏底物利用改变的证据。在这个早期阶段，LVEF 没有变化。（慢性心力衰竭的代谢干预；NCT00841139）。
