1Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA.
2Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
J Am Vet Med Assoc. 2023 Jul 26;261(11):1628-1637. doi: 10.2460/javma.23.04.0187. Print 2023 Nov 1.
Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM.
43 client-owned cats with subclinical HCM.
Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA.
No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups.
Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.
猫肥厚型心肌病（HCM）仍然是一种治疗进展甚微的疾病。雷帕霉素调节 mTOR 通路，可预防和逆转啮齿动物疾病模型中的心肌肥大。其在人类肾移植患者中的应用与降低心脏壁厚度有关。我们试图评估每周一次延迟释放（DR）雷帕霉素在 6 个月内对亚临床、非梗阻性 HCM 猫的超声心动图、生化和生物标志物反应的影响。
43 只患有亚临床 HCM 的患宠猫。
本双盲、多中心、随机、安慰剂对照临床试验纳入的猫被分配到低或高剂量 DR 雷帕霉素或安慰剂组。猫接受了体格检查、生活质量评估、血压、血液学、生化、总 T4、尿液分析、N 末端 pro-B 型利钠肽和心脏肌钙蛋白 I 的检测，时间点分别为基线和第 60、120 和 180 天。在筛查和第 180 天检测果糖胺。所有时间点（第 120 天除外）都进行了超声心动图检查。使用重复测量方差分析比较了结局变量。
在基线时，各组之间的人口统计学、超声心动图或临床病理值均无显著差异，证实了随机分组的成功。在第 180 天，主要研究结果变量，即任意部位的左心室心肌壁最大厚度，在低剂量 DR 雷帕霉素组与安慰剂组相比显著降低（P =.01）。口服 DR 雷帕霉素耐受性良好，各组之间不良反应无显著差异。
结果表明，DR 雷帕霉素耐受性良好，可能预防或延缓亚临床 HCM 猫的左心室肥厚进展。需要进一步研究来证实和进一步描述这些结果。
