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Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease.

Methods

We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment.

Results

Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group.

Conclusions

Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

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Abbreviations

CSNA:

Cardiac sympathetic nerve activity

STEMI:

ST-segment elevation myocardial infarction

MIBG:

Metaiodobenzylguanidine

LV:

Left ventricular

PIIINP:

Procollagen type III amino terminal peptide

H/M:

Heart/mediastinum count

WR:

Washout rate

TDS:

Total defect score

RDS:

Regional defect score

RDSI:

Regional defect score index

References

  1. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993;328:673-9.

    Article  CAS  Google Scholar 

  2. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, et al. Randomized study with the sirolimus-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773-80.

    Article  CAS  Google Scholar 

  3. Thomas JA, Marks BH. Plasma norepinephrine in congestive heart failure. Am J Cardiol 1978;41:233-43.

    Article  CAS  Google Scholar 

  4. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001-9.

    Article  CAS  Google Scholar 

  5. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57.

  6. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.

    Article  CAS  Google Scholar 

  7. Di Sciascio G, Patti G, Pasceri V, Gaspardone A, Colonna G, Montinaro A. Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: Results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. J Am Coll Cardiol 2009;54:558-65.

    Article  Google Scholar 

  8. Ellis SG, Chew D, Chan A, Whitlow PL, Schneider JP, Topol EJ. Death following creatine kinase-MB elevation after coronary intervention: Identification of an early risk period: Importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy. Circulation 2002;106:1205-10.

    Article  CAS  Google Scholar 

  9. Kodama Y, Kitta Y, Nakamura T, Takano H, Umetani K, Fujioka D, et al. Atorvastatin increases plasma soluble Fms-like tyrosine kinase-1 and decreases vascular endothelial growth factor and placental growth factor in association with improvement of ventricular function in acute myocardial infarction. J Am Coll Cardiol 2006;48:43-50.

    Article  CAS  Google Scholar 

  10. Sakata K, Mochizuki M, Yoshida H, Nawada R, Ohbayashi K, Ishikawa J, et al. Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction. Eur J Nucl Med 2000;27:1641-9.

    Article  CAS  Google Scholar 

  11. Matsunari I, Schricke U, Bengel FM, Haase HU, Barthel P, Schmidt G, et al. Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes. Circulation 2000;101:2579-85.

    Article  CAS  Google Scholar 

  12. Kasama S, Toyama T, Sumino H, Kumakura H, Takayama Y, Minami K, et al. Prognostic value of cardiac sympathetic nerve activity evaluated by [123I]m-iodobenzylguanidine imaging in patients with ST-segment elevation myocardial infarction. Heart 2011;97:20-6.

    Article  Google Scholar 

  13. Takeishi Y, Atsumi H, Fujiwara S, Takahashi K, Tomoike H. ACE inhibition reduces cardiac iodine-123-MIBG release in heart failure. J Nucl Med 1997;38:1085-9.

    CAS  PubMed  Google Scholar 

  14. Toyama T, Hoshizaki H, Seki R, Isobe N, Adachi H, Naito S, et al. Efficacy of carvedilol treatment on cardiac function and cardiac sympathetic nerve activity in patients with dilated cardiomyopathy: Comparison with metoprolol therapy. J Nucl Med 2003;44:1604-11.

    CAS  PubMed  Google Scholar 

  15. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, et al. Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol 2003;41:574-81.

    Article  CAS  Google Scholar 

  16. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, et al. Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction. J Am Coll Cardiol 2005;45:661-7.

    Article  CAS  Google Scholar 

  17. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, et al. Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction. J Am Coll Cardiol 2007;49:667-74.

    Article  CAS  Google Scholar 

  18. Kasama S, Toyama T, Sumino H, Kumakura H, Takayama Y, Minami K, et al. Effects of mineralocorticoid receptor antagonist spironolactone on cardiac sympathetic nerve activity and prognosis in patients with chronic heart failure. Int J Cardiol 2013;167:244-9.

    Article  Google Scholar 

  19. Pliquett RU, Cornish KG, Peuler JD, Zucker IH. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation 2003;107:2493-8.

    Article  CAS  Google Scholar 

  20. Lee TM, Lin MS, Chang NC. Effect of pravastatin on sympathetic reinnervation in postinfarcted rats. Am J Physiol Heart Circ Physiol 2007;293:H3617-26.

    Article  CAS  Google Scholar 

  21. Kang CS, Chen CC, Lin CC, Chang NC, Lee TM. Effect of ATP-sensitive potassium channel agonists on sympathetic hyperinnervation in postinfarcted rat hearts. Am J Physiol Heart Circ Physiol 2009;296:H1949-59.

    Article  CAS  Google Scholar 

  22. Jacobson AF, White S, Travin MI, Tseng C. Impact of concomitant medication use on myocardial 123I-mIBG imaging results in patients with heart failure. Nucl Med Commun 2017;38:141-8.

    Article  Google Scholar 

  23. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1046-81.

    PubMed  Google Scholar 

  24. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358-67.

    Article  CAS  Google Scholar 

  25. Kasama S, Toyama T, Sumino H, Kumakura H, Takayama Y, Ichikawa S, et al. Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction. J Nucl Med 2007;48:1676-82.

    Article  Google Scholar 

  26. Kasama S, Toyama T, Sumino H, Kumakura H, Takayama Y, Minami K, et al. Effects of spironolactone on cardiac sympathetic nerve activity and left ventricular remodelling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction. Heart 2011;97:817-22.

    Article  CAS  Google Scholar 

  27. Luellen JK, Shadish WR, Clark MH. Propensity scores: An introduction and experimental test. Eval Rev 2005;29:530-58.

    Article  Google Scholar 

  28. Mann DL. Inflammatory mediators and the failing heart: Past, present, and the foreseeable future. Circ Res 2002;91:988-98.

    Article  CAS  Google Scholar 

  29. Lefer DJ. Statins as potent antiinflammatory drugs. Circulation 2002;106:2041-2.

    Article  Google Scholar 

  30. Bolognese L, Neskovic AN, Parodi G, Cerisano G, Buonamici P, Santoro GM, et al. Left ventricular remodeling after primary coronary angioplasty: Patterns of left ventricular dilation and long-term prognostic implications. Circulation 2002;106:2351-7.

    Article  Google Scholar 

  31. Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergic neuron-blocking agents: Adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med 1980;21:349-53.

    CAS  PubMed  Google Scholar 

  32. Burgdorf C, Dendorfer A, Kurz T, Schömig E, Stölting I, Schütte F, et al. Role of neuronal KATP channels and extraneuronal monoamine transporter on norepinephrine overflow in a model of myocardial low flow ischemia. J Pharmacol Exp Ther 2004;309:42-8.

    Article  CAS  Google Scholar 

  33. Lardizabal JA, Deedwania PC. The anti-ischemic and anti-anginal properties of statins. Curr Atheroscler Rep 2011;13:43-50.

    Article  CAS  Google Scholar 

  34. Aikawa T, Naya M, Obara M, Oyama-Manabe N, Manabe O, et al. Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study. Eur J Nucl Med Mol Imaging 2017;44:1897-905.

    Article  CAS  Google Scholar 

  35. Kramer CM, Nicol PD, Rogers WJ, Suzuki MM, Shaffer A, Theobald TM, et al. Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling. J Am Coll Cardiol 1997;30(4):1079-85.

    Article  CAS  Google Scholar 

  36. Klappacher G, Franzen P, Haab D, Mehrabi M, Binder M, Plesch K, et al. Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol 1995;75:913-8.

    Article  CAS  Google Scholar 

  37. Host NB, Jensen LT, Bendixen PM, Jensen SE, Koldkjaer OG, Simonsen EE. The aminoterminal propeptide of type III procollagen provides new information on prognosis after acute myocardial infarction. Am J Cardiol 1995;76:869-73.

    Article  CAS  Google Scholar 

  38. Tamaki N, Kuge Y, Yoshinaga K. Molecular imaging in heart failure patients. Clin Transl Imaging 2013;1:341-51.

    Article  Google Scholar 

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Disclosure

The authors have declared that they have no financial conflicts of interest.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Shinya Takahashi MD, Shu Kasama MD, Takuji Toyama MD & Masahiko Kurabayashi MD

  2. Institute for Clinical and Translational Science, Nara Medical University Hospital, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Shu Kasama MD, Shota Suzuki MPH, Yukie Ito CN & Masato Kasahara MD

  3. Second Department of Internal Medicine (Cardiology), Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan

    Tomoaki Nakata MD

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  1. Shinya Takahashi MD
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Takahashi, S., Kasama, S., Toyama, T. et al. Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol. J. Nucl. Cardiol. 28, 1449–1457 (2021). https://doi.org/10.1007/s12350-019-01857-y

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