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Multicenter Study
. 2023 Jul 26;261(11):1628-1637.
doi: 10.2460/javma.23.04.0187. Print 2023 Nov 1.

Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial

Joanna L Kaplan  1 , Victor N Rivas  1   2 , Ashley L Walker  1 , Louise Grubb  3 , Aisling Farrell  3 , Stuart Fitzgerald  3 , Susan Kennedy  3 , Carina E Jauregui  1   2 , Amanda E Crofton  1 , Chris McLaughlin  2 , Rachel Van Zile  2 , Teresa C DeFrancesco  2 , Kathryn M Meurs  2 , Joshua A Stern  1   2
Affiliations
Multicenter Study

Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic cardiomyopathy: results of the RAPACAT trial

Joanna L Kaplan et al. J Am Vet Med Assoc. .

Abstract

Objective: 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.

Animals: 43 client-owned cats with subclinical HCM.

Methods: 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.

Results: 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.

Clinical relevance: 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.

Keywords: HCM; cat; mTOR; occult; sirolimus.

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Figures

Figure 1—
Figure 1—
Temporal comparison of maximum wall thickness (MWT; mm) at any location between placebo (gray) and low- (pink) and high-dose (teal) delayed-release rapamycin. The * and ** denote a P value of .05 for pooled dose groups compared to placebo and .01 for low dose compared to placebo, respectively. Values are reported as mean ± SEM.
Figure 2—
Figure 2—
Pearson correlation of baseline N-terminal pro-B-type natriuretic peptide (NTproBNP) with change in MWT (mm) from baseline to day 180. The best-fit line is shown in bright pink. The 95% CI is shaded in light pink.
Figure 3—
Figure 3—
Baseline NTproBNP values and MWT changes (%) from baseline to day 180 in placebo (gray) and low-(pink) and high-dose (teal) delayed-release rapamycin groups. Color-matched curved best-fit lines are shown for each dose group by use of a nonlinear regression model and least-squares method in Prism (version 9.0; GraphPad Software). A dashed vertical line at 100 pmol/L denotes the cut point used for an abnormal NTproBNP in cats.
See this image and copyright information in PMC

References

    1. Kittleson MD, Côté E. The feline cardiomyopathies: 2. hypertrophic cardiomyopathy. J Feline Med Surg. 2021;23(11):1028–1051. doi:10.1177/1098612X211020162 - DOI - PMC - PubMed
    1. Luis Fuentes V, Abbott J, Chetboul V, et al. ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats. J Vet Intern Med. 2020;34(3):1062–1077. doi:10.1111/jvim.15745 - DOI - PMC - PubMed
    1. Payne JR, Brodbelt DC, Luis Fuentes V. Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study). J Vet Cardiol. 2015;17(suppl 1):S244–S257. doi:10.1016/j.jvc.2015.03.008 - DOI - PubMed
    1. Fox PR, Keene BW, Lamb K, et al. International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: the REVEAL Study. J Vet Intern Med. 2018;32(3):930–943. doi:10.1111/jvim.15122 - DOI - PMC - PubMed
    1. Sciarretta S, Forte M, Frati G, Sadoshima J. New insights into the role of mTOR signaling in the cardiovascular system. Circ Res. 2018;122(3):489–505. doi:10.1161/CIRCRESAHA.117.311147 - DOI - PMC - PubMed

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