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The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

We previously reported that ranolazine improved myocardial ischemia during exercise myocardial perfusion imaging (MPI). Since the mechanism of reversible perfusion defects is different in exercise than vasodilator MPI, and based on the mechanism of action of ranolazine, we hypothesized that vasodilator stress MPI may fail to show improvement in myocardial perfusion pattern.

Methods

Patients (n = 18) with known coronary artery disease and with reversible perfusion defects on a clinically indicated vasodilator stress MPI were re-studied 4 weeks after ranolazine (500-1000 mg PO BID) was added to their conventional treatment in an open-label trial. Perfusion pattern was assessed using automated methods.

Results

The baseline left ventricular ejection fraction was 59% ± 14%. The total perfusion defect (measured by polar maps) was 22% ± 13% before and 21% ± 16% of LV myocardium after treatment (P = NS). The reversible defect size was 14% ± 10% before and 14% ± 11% of LV myocardium after treatment (P = NS). The automated-derived summed stress score was 12 ± 8 before and 12 ± 10 after treatment (P = NS) and the automated-derived summed difference score was 6 ± 5 before and 6 ± 5 after treatment (P = NS). Only 3 patients showed a decrease in reversible perfusion defect size with treatment.

Conclusion

Vasodilator stress MPI failed to show improvement in perfusion pattern after ranolazine treatment in most patients with baseline reversible defects. This is consistent with the unique anti-ischemic mechanism of ranolazine, which acts on the late I Na channel.

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References

  1. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics—2008 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e25-146.

    Article  PubMed  Google Scholar 

  2. Zoghbi GJ, Dorfman TA, Iskandrian AE. The effects of medications on myocardial perfusion. J Am Coll Cardiol 2008;52:401-16.

    Article  PubMed  CAS  Google Scholar 

  3. Allely MC, Alps BJ. Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion. Br J Pharmacol 1990;99:5-6.

    PubMed  CAS  Google Scholar 

  4. Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: Effects of the late sodium current inhibitor ranolazine. Heart 2006;92:6-14.

    Article  Google Scholar 

  5. Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: A randomized controlled trial. JAMA 2004;291:309-16.

    Article  PubMed  CAS  Google Scholar 

  6. Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 2004;43:1375-82.

    Article  PubMed  CAS  Google Scholar 

  7. Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol 2006;41:1031-8.

    Article  PubMed  CAS  Google Scholar 

  8. Hale SL, Leeka JA, Kloner RA. Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel. J Pharmacol Exp Ther 2006;318:418-23.

    Article  PubMed  CAS  Google Scholar 

  9. Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol 2008;44:954-67.

    Article  PubMed  CAS  Google Scholar 

  10. Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: The Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol 2007;49:1027-34.

    Article  PubMed  CAS  Google Scholar 

  11. Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: The ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol 2006;48:566-75.

    Article  PubMed  CAS  Google Scholar 

  12. Zacharowski K, Blackburn B, Thiemermann C. Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin T release in the rat. Eur J Pharmacol 2001;418:105-10.

    Article  PubMed  CAS  Google Scholar 

  13. Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging 2009;2:1301-9.

    Article  PubMed  Google Scholar 

  14. Al Jaroudi W, Iskandrian AE. Regadenoson: A new myocardial stress agent. J Am Coll Cardiol 2009;54:1123-30.

    Article  PubMed  CAS  Google Scholar 

  15. Iskandrian AE, Garcia EV. Nuclear cardiac imaging: principles and applications. 4th ed. Oxford: Oxford University Press; 2008.

    Google Scholar 

  16. Mahmarian JJ, Cerqueira MD, Iskandrian AE, et al. Regadenoson induces comparable left ventricular perfusion defects as adenosine: A quantitative analysis from the ADVANCE MPI 2 trial. JACC Cardiovasc Imaging 2009;2:959-68.

    Article  PubMed  Google Scholar 

  17. Berecki G, Zegers JG, Bhuiyan ZA, Verkerk AO, Wilders R, van Ginneken AC. Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique. J Physiol 2006;570:237-50.

    PubMed  CAS  Google Scholar 

  18. Kunze DL, Lacerda AE, Wilson DL, Brown AM. Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels. J Gen Physiol 1985;86:691-719.

    Article  PubMed  CAS  Google Scholar 

  19. Zaza A, Belardinelli L, Shryock JC. Pathophysiology and pharmacology of the cardiac “late sodium current”. Pharmacol Ther 2008;119:326-39.

    Article  PubMed  CAS  Google Scholar 

  20. Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 2005;95:311-6.

    Article  PubMed  CAS  Google Scholar 

  21. Stone PH, Chaitman BR, Stocke K, Sano J, DeVault A, Koch GG. The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease. J Am Coll Cardiol 2010;56:934-42.

    Article  PubMed  CAS  Google Scholar 

  22. Iskandrian AE, Heo J, Mehta D, et al. Gated SPECT perfusion imaging for the simultaneous assessment of myocardial perfusion and ventricular function in the BARI 2D trial: An initial report from the Nuclear Core Laboratory. J Nucl Cardiol 2006;13:83-90.

    Article  PubMed  Google Scholar 

  23. Mahmarian JJ, Dakik HA, Filipchuk NG, et al. An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction. J Am Coll Cardiol 2006;48:2458-67.

    Article  PubMed  Google Scholar 

  24. Shaw LJ, Berman DS, Maron DJ, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: Results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283-91.

    Article  PubMed  Google Scholar 

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Acknowledgment

We acknowledge the help of Misty Pruitt, RN in data collection.

Disclosures

AEI is a consultant to Gilead Sciences Inc, Foster City, CA and LB is an employee of Gilead Sciences Inc, Foster City, CA. All other authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Division of Cardiovascular Disease, University of Alabama at Birmingham, 314 LHRB, 1900 University BLVD, Birmingham, AL, 35294-0007, USA

    Rajesh Venkataraman MD, MPH, Wael Aljaroudi MD, Jaekyeong Heo MD & Ami E. Iskandrian MD, MACC

  2. Gilead Sciences Inc, Foster City, CA, USA

    Luiz Belardinelli MD

Authors
  1. Rajesh Venkataraman MD, MPH
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  2. Wael Aljaroudi MD
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  3. Luiz Belardinelli MD
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  4. Jaekyeong Heo MD
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  5. Ami E. Iskandrian MD, MACC
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Corresponding author

Correspondence to Rajesh Venkataraman MD, MPH.

Additional information

The study was funded by a grant from Gilead Sciences Inc, Foster City, CA. The study design, data collection, interpretation, and reporting were the responsibility of the UAB investigators.

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Venkataraman, R., Aljaroudi, W., Belardinelli, L. et al. The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality. J. Nucl. Cardiol. 18, 456–462 (2011). https://doi.org/10.1007/s12350-011-9364-1

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  • DOI: https://doi.org/10.1007/s12350-011-9364-1

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