The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Metabolic Modulation With Perhexiline in Chronic Heart Failure: A Randomized, Controlled Trial of Short-Term Use of a Novel Treatment
Open accessAbstract
Background— Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. Methods and Results— In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (V̇ o 2 max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31 P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in V̇ o 2 max (16.1±0.6 to 18.8±1.1 mL · kg −1 · min −1 ; P <0.001), quality of life (Minnesota score reduction from 45±5 to 34±5; P =0.04), and left ventricular ejection fraction (24±1% to 34±2%; P <0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. Conclusions— In patients with CHF, metabolic modulation with perhexiline improved V̇ o 2 max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.
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Exercise limitation in chronic heart failure: Central role of the periphery
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Cited by
Cardiac Energy Metabolism in Heart Failure
Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R., & Abel, E. D. (2021) · Circulation Research · doi:10.1161/circresaha.121.318241 · Cited by 1,373
Cardiovascular remodelling in coronary artery disease and heart failure
Heusch, G., Libby, P., Gersh, B., Yellon, D., Böhm, M., Lopaschuk, G., & Opie, L. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60107-0 · Cited by 734
Tham, Y. K., Bernardo, B. C., Ooi, J. Y. Y., Weeks, K. L., & McMullen, J. R. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1477-x · Cited by 708
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L.-L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 399
Myocardial fatty acid metabolism and cardiac performance in heart failure
Tuunanen, H., Ukkonen, H., & Knuuti, J. (2008) · Current Cardiology Reports · doi:10.1007/s11886-008-0024-2 · Cited by 49
Metadata
- Authors
- Lee, L., Campbell, R., Scheuermann-Freestone, M., Taylor, R., Gunaruwan, P., Williams, L., Ashrafian, H., Horowitz, J., Fraser, A. G., Clarke, K., & Frenneaux, M.
- Venue
- Circulation
- Published
- 2005-11-22
- Volume
- 112
- Issue
- 21
- Pages
- 3280-3288
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2154258710
- Cited by
- 357
- References
- 36
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lee, L., Campbell, R., Scheuermann-Freestone, M., Taylor, R., Gunaruwan, P., Williams, L., Ashrafian, H., Horowitz, J., Fraser, A. G., Clarke, K., & Frenneaux, M. (2005). Metabolic Modulation With Perhexiline in Chronic Heart Failure: A Randomized, Controlled Trial of Short-Term Use of a Novel Treatment. Circulation. https://doi.org/10.1161/circulationaha.105.551457
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