Reverse Remodeling of Methamphetamine-Associated Cardiomyopathy: An Update on Mechanisms for Recovery

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John R. Richards, MD Aaron R. Danielson, MD Rory P. Stuart, MD Andrew E. Richards Erik G. Laurin, MD


Methamphetamine (MA) use continues to rise worldwide. The adverse effects of MA on the cardiovascular system include cardiomyopathy, dysrhythmias, coronary arterial vasospasm, and atherosclerosis. Methamphetamine-associated cardiomyopathy (MACM) affects predominantly younger male patients and is responsible for an increasing proportion of heart failure emergency department visits, hospital admissions/readmissions, morbidity, and mortality. Reverse remodeling of MACM and full cardiac recovery is achievable in patients who cease using MA and remain abstinent with self-direction, cognitive behavioral therapy, brief interventions, contingency management, motivational interviewing, and residential rehabilitation. Recovery is further enhanced by the addition of an exercise program and guideline-based pharmacotherapy for heart failure, which includes β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Alternative heart failure treatment with isosorbide dinitrate plus hydralazine, ivabradine, vericiguat, and omecamtiv mecarbil represent further adjuncts which may promote reverse remodeling. Antioxidant compounds such as coenzyme-Q10, omega-3 polyunsaturated fatty acids, resveratrol, and cannabidiol may aid in cardiac restoration. Diet changes, metformin and glucose control, stem cell therapy, melatonin, and sleep quality improvement are further steps on the road to recovery. In this article we review the cardiotoxicity of MA, pathogenesis of MACM, and evidence behind pharmacologic and lifestyle interventions to reverse its progression.

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RICHARDS, John R. et al. Reverse Remodeling of Methamphetamine-Associated Cardiomyopathy: An Update on Mechanisms for Recovery. Medical Research Archives, [S.l.], v. 12, n. 6, june 2024. ISSN 2375-1924. Available at: <>. Date accessed: 22 july 2024. doi:
Research Articles


1. Won S, Hong RA, Shohet RV, Seto TB, Parikh NI. Methamphetamine‐Associated Cardiomyo¬pathy. Clin Cardiol. 2013;36(12):737-742. Doi:10.1002/clc.22195
2. Latif A, Ahsan MJ, Lateef N, et al. Is Metham-phetamine-Linked Cardiomyopathy an Emerg¬ing Epidemic for New Generation? Curr Probl Cardiol. 2023;48(1):101042. Doi:10.1016/j.cpcardiol.2021.101042
3. Stoneberg DM, Shukla RK, Magness MB. Global Methamphetamine Trends: An Evolving Problem. Int Crim Justice Rev. 2018;28(2):136-161. Doi:10.1177/1057567717730104
4. Reddy P, Elkayam U. The Hidden Cost of Meth: Appraising the Socioeconomic Burden of Meth¬amphetamine-Associated Cardiomyopathy. Circ Cardiovasc Qual Outcomes. 2021;14(7):e008214. Doi:10.1161/CIR¬COUTCOMES.121.008214
5. Manja V, Nrusimha A, Gao Y, et al. Metham-phetamine-associated heart failure: a system-atic review of observational studies. Heart. 2023;109(3):168-177. Doi:10.1136/heartjnl-2022-321610
6. Manja V, Sandhu ATS, Frayne S, et al. Varia-tion in Methamphetamine-Associated Heart Failure Hospitalizations Across the United States. J Card Fail. 2024;30(1):91-94. Doi:10.1016/j.cardfail.2023.07.015
7. Zhao SX, Deluna A, Kelsey K, et al. Socioeco-nomic Burden of Rising Methamphetamine-As-sociated Heart Failure Hospitalizations in Cal-ifornia From 2008 to 2018. Circ Cardiovasc Qual Outcomes. 2021;14(7):e007638. Doi:10.1161/CIRCOUTCOMES.120.007638
8. Nishimura M, Ma J, Fox S, et al. Characteristics and Outcomes of Methamphetamine Abuse Among Veterans With Heart Failure. Am J Cardiol. 2019;124(6):907-911. Doi:10.1016/j.amjcard.2019.05.068
9. Rajs J, Falconer B. Cardiac lesions in intrave-nous drug addicts. Forensic Sci Int. 1979;13:193-209. Doi:10.1016/0379-0738(79)90288-3
10.Kalant H, Kalant OJ. Death in amphetamine us-ers: causes and rates. Can Med Assoc J. 1975;112(3):299-304.
11.Chehab O, Ioannou A, Sawhney A, Rice A, Du-brey S. Reverse Takotsubo Cardiomyopathy and Cardiogenic Shock Associated With Meth¬amphetamine Consumption. J Emerg Med. 2017;53(5):e81-e83. Doi:10.1016/j.jemermed.2017.06.027
12. Madias JE. Methamphetamine-triggered Tako-tsubo syndrome and methamphetamine-asso-ciated cardiomyopathy: a continuum? Intern Med J. 2016;46(6):752-753. Doi:10.1111/imj.13102
13. Tobolski J, Sawyer DB, Song SJ, Afari ME. Car¬diovascular disease associated with metham¬phetamine use: a review. Heart Fail Rev. 2022;27(6):2059-2065. Doi:10.1007/s10741-022-10261-7
14. Jacobs LJ. Reversible dilated cardiomyopathy induced by methamphetamine. Clin Cardiol. 1989;12(12):725-727. Doi:10.1002/clc.4960121211
15. Voskoboinik A, Ihle JF, Bloom JE, Kaye DM. Methamphetamine-associated cardiomyopa-thy: patterns and predictors of recovery. Intern Med J. 2016;46(6):723-727. Doi:10.1111/imj.13050
16. Panenka WJ, Procyshyn RM, Lecomte T, et al. Methamphetamine use: A comprehensive re-view of molecular, preclinical and clinical find¬ings. Drug Alcohol Depend. 2013;129(3):167-179. Doi:10.1016/j.dru-galcdep.2012.11.016
17. Cruickshank CC, Dyer KR. A review of the clini-cal pharmacology of methamphetamine. Ad-diction. 2009;104(7):1085-1099. Doi:10.1111/j.1360-0443.2009.02564.x
18. Yang X, Wang Y, Li Q, et al. The Main Molecu¬lar Mechanisms Underlying Methampheta¬mine- Induced Neurotoxicity and Implications for Pharmacological Treatment. Front Mol Neurosci. 2018;11:186. Doi:10.3389/fnmol.2018.00186
19. Abdullah CS, Remex NS, Aishwarya R, et al. Mi¬tochondrial dysfunction and autophagy acti¬vation are associated with cardiomyopathy developed by extended methamphetamine self-administration in rats. Redox Biol. 2022;58:102523. Doi:10.1016/¬dox.2022.102523
20. Lord KC, Shenouda SK, McIlwain E, Charalam-pidis D, Lucchesi PA, Varner KJ. Oxidative stress contributes to methamphetamine-in-duced left ventricular dysfunction. Cardiovasc Res. 2010;87(1):111-118. Doi:10.1093/cvr/cvq043
21. Krasnova IN, Cadet JL. Methamphetamine tox¬icity and messengers of death. Brain Res Rev. 2009;60(2):379-407. Doi:10.1016/j.brainresrev.2009.03.002
22. Reddy PK, Chau E, Patel SV, Yang K, Ng TM, Elkayam U. Characteristics of Methampheta-mine-associated Cardiomyopathy and the Im-pact of Methamphetamine Use on Cardiac Dysfunction. Am J Cardiol. 2021;154:86-91. Doi:10.1016/j.amjcard.2021.06.001
23. Brown JM, Yamamoto BK. Effects of ampheta-mines on mitochondrial function: role of free radicals and oxidative stress. Pharmacol Ther. 2003;99(1):45-53. Doi:10.1016/S0163-7258(03)00052-4
24. Kevil CG, Goeders NE, Woolard MD, et al. Methamphetamine Use and Cardiovascular Disease: In Search of Answers. Arterioscler Thromb Vasc Biol. 2019;39(9):1739-1746. Doi:10.1161/ATVBAHA.119.312461
25. Turdi S, Schamber RM, Roe ND, Chew HG, Cul¬ver B, Ren J. Acute methamphetamine expo¬sure inhibits cardiac contractile function. Toxi¬col Lett. 2009;189(2):152-158. Doi:10.1016/j.toxlet.2009.05.015
26. Zhang J, Nguyen AH, Jilani D, et al. Consecutive treatments of methamphetamine promote the development of cardiac pathological symp¬toms in zebrafish. PloS One. 2023;18(11):e0294322. Doi:10.1371/jour¬nal.pone.0294322
27. Yi S hua, Ren L, Yang T tong, Liu L, Wang H, Liu Q. Myocardial lesions after long-term admin¬istration of methamphetamine in rats. Chin Med Sci J. 2008;23(4):239-243. Doi:10.1016/S1001-9294(09)60046-8
28. Molh AKS, Ting LC, Khan J, Al-Jashamy K, Jaafar H, Islam MN. Histopathological Studies of Cardiac Lesions after an Acute High Dose Administration of Methamphetamine. Malays J Med Sci MJMS. 2008;15(1):23-30.
29. He SY, Matoba R, Fujitani N, Sodesaki K ichiro, Onishi S. Cardiac Muscle Lesions Associated with Chronic Administration of Methampheta¬mine in Rats. Am J Forensic Med Pathol. 1996;17(2):155.
30. Akhgari M, Mobaraki H, Etemadi-Aleagha A. Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths. Daru J Fac Pharm Tehran Univ Med Sci. 2017;25(1):5. Doi:10.1186/s40199-017-0170-4
31. Islam MN, Kuroki H, Hongcheng B, et al. Car-diac lesions and their reversibility after long term administration of methamphetamine. Fo-rensic Sci Int. 1995;75(1):29-43. Doi:10.1016/0379-0738(95)01765-B
32. Sliman S, Waalen J, Shaw D. Methampheta-mine-Associated Congestive Heart Failure: In-creasing Prevalence and Relationship of Clini¬cal Outcomes to Continued Use or Abstinence. Cardiovasc Toxicol. 2016;16(4):381-389. Doi:10.1007/s12012-015-9350-y
33. Vaupel DB, Schindler CW, Chefer S, et al. De-layed emergence of methamphetamine’s en-hanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence. Drug Alcohol Depend. 2016;159:181. Doi:10.1016/j.dru-galcdep.2015.12.008
34. Schürer S, Klingel K, Sandri M, et al. Clinical Characteristics, Histopathological Features, and Clinical Outcome of Methamphetamine-Associated Cardiomyopathy. JACC Heart Fail. 2017;5(6):435-445. Doi:10.1016/j.jchf.2017.02.017
35. Pujol-López M, Ortega-Paz L, Flores-Umanzor EJ, Perea RJ, Bosch X. Cardiac Magnetic Res-onance as an Alternative to Endomyocardial Biopsy to Predict Recoverability of Left Ven-tricular Function in Methamphetamine- Associ-ated Cardiomyopathy. JACC Heart Fail. 2017;5(11):853-854. Doi:10.1016/j.jchf.2017.08.009
36. Paulus MP, Stewart JL. Neurobiology, Clinical Presentation, and Treatment of Methampheta¬mine Use Disorder: A Review. JAMA Psychiatry. 2020;77(9):959. Doi:10.1001/jamapsychia¬try.2020.0246
37. Lee NK, Jenner L, Harney A, Cameron J. Phar-macotherapy for amphetamine dependence: A systematic review. Drug Alcohol Depend. 2018;191:309-337. Doi:10.1016/j.dru-galcdep.2018.06.038
38. Chan B, Freeman M, Kondo K, et al. Pharma-cotherapy for methampheta-mine/amphetamine use disorder-a systematic review and meta-analysis. Addict Abingdon Engl. 2019;114(12):2122-2136. Doi:10.1111/add.14755
39. Hossain MK, Davidson M, Kypreos E, et al. Im-munotherapies for the Treatment of Drug Ad-diction. Vaccines. 2022;10(11):1778. Doi:10.3390/vaccines10111778
40. De Crescenzo F, Ciabattini M, D’Alò GL, et al. Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A sys-tematic review and network meta-analysis. PLoS Med. 2018;15(12):e1002715. Doi:10.1371/journal.pmed.1002715
41. Harada T, Tsutomi H, Mori R, Wilson DB. Cog-nitive-behavioural treatment for ampheta-mine-type stimulants (ATS)-use disorders. Cochrane Database Syst Rev. 2018;12(12):CD011315. Doi:10.1002/14651858.CD011315.pub2
42. Cook R, Quinn B, Heinzerling K, Shoptaw S. Dropout in clinical trials of pharmacological treatment for methamphetamine dependence: the role of initial abstinence. Addict Abingdon Engl. 2017;112(6):1077-1085. Doi:10.1111/add.13765
43. Rawson RA, Chudzynski J, Gonzales R, et al. The Impact of Exercise On Depression and Anxiety Symptoms Among Abstinent Methampheta¬mine-Dependent Individuals in A Residential Treatment Setting. J Subst Abuse Treat. 2015;57:36-40. Doi:10.1016/j.jsat.2015.04.007
44. Wang D, Zhou C, Zhao M, Wu X, Chang YK. Dose-response relationships between exercise intensity, cravings, and inhibitory control in methamphetamine dependence: An ERPs study. Drug Alcohol Depend. 2016;161:331-339. Doi:10.1016/j.dru-galcdep.2016.02.023
45. Morais APD, Pita IR, Fontes‐Ribeiro CA, Pereira FC. The neurobiological mechanisms of physi¬cal exercise in methamphetamine addiction. CNS Neurosci Ther. 2017;24(2):85-97. Doi:10.1111/cns.12788
46. Tuomainen T, Tavi P. The role of cardiac energy metabolism in cardiac hypertrophy and fail¬ure. Exp Cell Res. 2017;360(1):12-18. Doi:10.1016/j.yexcr.2017.03.052
47. Qi Z, Zheng Y, Chan JSK, Tse G, Liu T. Exercise-based cardiac rehabilitation for left ventricu¬lar function in patients with heart failure: A sys¬tematic review and meta-analysis. Curr Probl Cardiol. 2024;49(2):102210. Doi:10.1016/j.cpcardiol.2023.102210
48. O’Connor CM, Whellan DJ, Lee KL, et al. Effi-cacy and safety of exercise training in patients with chronic heart failure: HF-ACTION ran¬domized controlled trial. JAMA. 2009;301(14):1439-1450. Doi:10.1001/jama.2009.454
49. Molloy CD, Long L, Mordi IR, et al. Exercise-based cardiac rehabilitation for adults with heart failure - 2023 Cochrane systematic re-view and meta-analysis. Eur J Heart Fail. 2023;25(12):2263-2273. Doi:10.1002/ejhf.3046
50. Callum K, Swinton P, Gorely T, Crabtree D, Leslie S. Physiological and psychological out-comes of high intensity interval training in pa-tients with heart failure compared to moderate continuous training and usual care: A system¬atic review with meta analysis. Heart Lung J Crit Care. 2024;64:117-127. Doi:10.1016/j.hrtlng.2023.12.002
51. Scarà A, Palamà Z, Robles AG, et al. Non-Phar¬macological Treatment of Heart Failure—From Physical Activity to Electrical Therapies: A Literature Review. J Cardiovasc Dev Dis. 2024;11(4):122. Doi:10.3390/jcdd11040122
52. Kyselovič J, Leddy JJ. Cardiac Fibrosis: The Beneficial Effects of Exercise in Cardiac Fibro¬sis. Adv Exp Med Biol. 2017;999:257-268. Doi:10.1007/978-981-10-4307-9_14
53. Li H, Wang C, Huang X, et al. Chan-Chuang and resistance exercise for drug rehabilita-tion: a randomized controlled trial among Chi¬nese male methamphetamine users. Front Pub¬lic Health. 2023;11:1180503. Doi:10.3389/fpubh.2023.1180503
54. Maddox TM, Januzzi JL, Allen LA, et al. 2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2024;83(15):1444-1488. Doi:10.1016/j.jacc.2023.12.024
55. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. Doi:10.1161/CIR.0000000000001063
56. McDonagh TA, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627-3639. Doi:10.1093/eurheartj/ehad195
57. Burnett H, Earley A, Voors AA, et al. Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Re¬duced Ejection Fraction: A Network Meta-Analysis. Circ Heart Fail. 2017;10(1):e003529. Doi:10.1161/CIR-CHEARTFAILURE.116.003529
58. Xu Y, Li W, Wan K, et al. Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardi-omyopathy. Circ Heart Fail. 2021;14(1):e007944. Doi:10.1161/CIR-CHEARTFAILURE.120.007944
59. Haseeb MT, Nouman Aslam M, Avanteeka F, et al. Comparison of Efficacy and Safety of An¬giotensin Receptor-Neprilysin Inhibitors in Pa¬tients With Heart Failure With Reduced Ejec¬tion Fraction: A Meta-Analysis. Cureus. 2023;15(3):e36392. Doi:10.7759/cu-reus.36392
60. Qin J, Wang W, Wei P, Huang P, Lin R, Yue J. Effects of sacubitril-valsartan on heart failure patients with mid-range ejection fractions: A systematic review and meta-analysis. Front Pharmacol. 2022;13:982372. Doi:10.3389/fphar.2022.982372
61. Frankenstein L, Seide S, Täger T, et al. Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart fail¬ure (RESEARCH): a systematic review and net¬work meta-analysis of randomized controlled trials. Heart Fail Rev. 2020;25(2):161-171. Doi:10.1007/s10741-019-09832-y
62. Xie L, Xiao H, Zhao M, Tang S, Qiu Y. Retro-spective study on the short-term efficacy of different doses of Spironolactone in patients with heart failure of ischemic cardiomyopath and the influence of ventricular remodeling markers. Am J Cardiovasc Dis. 2024;14(1):21-28. Doi:10.62347/SYIX9692
63. Richards JR. Beta-Blockers: Physiological, Phar-macological and Therapeutic Implications. Nova Science Publishers, Incorporated; 2018. Ac¬cessed April 29, 2024.
64. de Oliveira MT, Baptista R, Chavez-Leal SA, Bonatto MG. Heart failure management with β-blockers: can we do better? Curr Med Res Opin. 2024;40(sup1):43-54. Doi:10.1080/03007995.2024.2318002
65. Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ. Treatment of toxicity from amphetamines, related derivatives, and analogues: A systematic clinical review. Drug Alcohol Depend. 2015;150:1-13. Doi:10.1016/j.drugalcdep.2015.01.040
66. Doughty RN, White HD. Carvedilol: use in chronic heart failure. Expert Rev Cardiovasc Ther. 2007;5(1):21-31. Doi:10.1586/14779072.5.1.21
67. Richards JR. Beta-Blockers and Evidence-Based Guidelines for the Pharmacological Manage¬ment of Acute Methamphetamine-Related Dis¬orders and Toxicity. Pharmacopsychiatry. 2018;51(3):108. Doi:10.1055/s-0043-118413
68. Colucci WS, Kolias TJ, Adams KF, et al. Metoprolol reverses left ventricular remodel-ing in patients with asymptomatic systolic dys¬function: the REversal of VEntricular Remodel¬ing with Toprol-XL (REVERT) trial. Circulation. 2007;116(1):49-56. Doi:10.1161/CIRCULA-TIONAHA.106.666016
69. Kaya MG, Sarli B, Akpek M, et al. Evaluation of beta-blockers on left ventricular dyssyn-chrony and reverse remodeling in idiopathic dilated cardiomyopathy: A randomized trial of carvedilol and metoprolol. Cardiol J. 2014;21(4):434-441. Doi:10.5603/CJ.a2013.0149
70. Chinnappa S, Maqbool A, Viswambharan H, Mooney A, Denby L, Drinkhill M. Beta Block-ade Prevents Cardiac Morphological and Mo¬lecular Remodelling in Experimental Uremia. Int J Mol Sci. 2023;25(1):373. Doi:10.3390/ijms25010373
71. Stougiannou TM, Christodoulou KC, Koufakis T, et al. Progenitor Cell Function and Cardiovas-cular Remodelling Induced by SGLT2 Inhibi-tors. Front Biosci Landmark Ed. 2024;29(4):145. Doi:10.31083/j.fbl2904145
72. Gao M, Bhatia K, Kapoor A, et al. SGLT2 Inhib¬itors, Functional Capacity, and Quality of Life in Patients With Heart Failure: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024;7(4):e245135. Doi:10.1001/jamanetworkopen.2024.5135
73. Singh S, Garg A, Tantry US, Bliden K, Gurbel PA, Gulati M. Cardiovascular Outcomes With Empagliflozin and Dapagliflozin in Patients Without Diabetes. Am J Cardiol. 2024;218:24-31. Doi:10.1016/
74. Adamou A, Chlorogiannis DD, Kyriakoulis IG, et al. Sodium-glucose cotransporter-2 inhibitors in heart failure patients across the range of body mass index: a systematic review and meta-analysis of randomized controlled trials. Intern Emerg Med. 2024;19(2):565-573. Doi:10.1007/s11739-024-03532-8
75. Kourek C, Briasoulis A, Papamichail A, et al. Be¬yond Quadruple Therapy and Current Thera¬peutic Strategies in Heart Failure with Re¬duced Ejection Fraction: Medical Therapies with Potential to Become Part of the Therapeu¬tic Armamentarium. Int J Mol Sci. 2024;25(6):3113. Doi:10.3390/ijms25063113
76. Amar M, Lam SW, Faulkenberg K, Perez A, Tang WHW, Williams JB. Captopril Versus Hydralazine-Isosorbide Dinitrate Vasodilator Protocols in Patients With Acute Decompen-sated Heart Failure Transitioning From Sodium Nitroprusside. J Card Fail. 2021;27(10):1053-1060. Doi:10.1016/j.cardfail.2021.05.007
77. Imamura T. Clinical Implications of Ivabradine in the Contemporary Era. Med Kaunas Lith. 2024;60(2):303. Doi:10.3390/medic-ina60020303
78. Wan H, Huang T, Zhang H, Wu Q. Effects of Ivabradine on Cardiac Remodeling in Patients With Stable Symptomatic Heart Failure: A Systematic Review and Meta-analysis. Clin Ther. 2020;42(12):2289-2297.e0. Doi:10.1016/j.clinthera.2020.10.005
79. Bryan Richard S, Huang B, Liu G, Yang Y, Luo S. Impact of ivabradine on the cardiac function of chronic heart failure reduced ejection frac¬tion: Meta-analysis of randomized controlled trials. Clin Cardiol. 2021;44(4):463-471. Doi:10.1002/clc.23581
80. Kang C, Lamb YN. Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. Am J Cardiovasc Drugs Drugs Devices Interv. 2022;22(4):451-459. Doi:10.1007/s40256-022-00538-5
81. Sahana U, Wehland M, Simonsen U, Schulz H, Grimm D. A Systematic Review of the Effect of Vericiguat on Patients with Heart Failure. Int J Mol Sci. 2023;24(14):11826. Doi:10.3390/ijms241411826
82. Jerkins T, McGill JB, Bell DSH. Heart failure and diabetes: Clinical significance and epidemiol¬ogy of this two-way association. Diabetes Obes Metab. 2023;25(S3):3-14. Doi:10.1111/dom.15062
83. Schulze PC, Drosatos K, Goldberg IJ. Lipid Use and Misuse by the Heart. Circ Res. 2016;118(11):1736-1751. Doi:10.1161/CIRCRESAHA.116.306842
84. Dihoum A, Rena G, Pearson ER, Lang CC, Mordi IR. Metformin: evidence from preclinical and clinical studies for potential novel applications in cardiovascular disease. Expert Opin Investig Drugs. Published online April 3, 2023. Ac¬cessed May 1, 2024.
85. Kamel AM, Sabry N, Farid S. Effect of metfor-min on left ventricular mass and functional pa¬rameters in non-diabetic patients: a meta-analysis of randomized clinical trials. BMC Cardiovasc Disord. 2022;22(1):405. Doi:10.1186/s12872-022-02845-w
86. Hosseini MJ, Arabiyan A, Mobassem S, Ghavimi H. Metformin attenuates depressive-like be¬haviour of methamphetamine withdrawal in mice: A mechanistic approach. World J Biol Psychiatry. 2023;24(3):209-222. Doi:10.1080/15622975.2022.2086294
87. Yang J, Zhang Z, Xie Z, et al. Metformin modu¬lates microbiota-derived inosine and amelio¬rates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice. Biomed Pharmacother. 2022;149:112837. Doi:10.1016/j.biopha.2022.112837
88. Niazi M, Galehdar N, Jamshidi M, Mohammadi R, Moayyedkazemi A. A Review of the Role of Statins in Heart Failure Treatment. Curr Clin Pharmacol. 2020;15(1):30-37. Doi:10.2174/1574884714666190802125627
89. Lee MMY, Sattar N, McMurray JJV, Packard CJ. Statins in the Prevention and Treatment of Heart Failure: a Review of the Evidence. Curr Atheroscler Rep. 2019;21(10):41. Doi:10.1007/s11883-019-0800-z
90. Liu G, Zheng XX, Xu YL, Lu J, Hui RT, Huang XH. Effects of lipophilic statins for heart failure: a meta-analysis of 13 randomised controlled tri¬als. Heart Lung Circ. 2014;23(10):970-977. Doi:10.1016/j.hlc.2014.05.005
91. Bielecka-Dabrowa A, Bytyçi I, Von Haehling S, et al. Association of statin use and clinical out¬comes in heart failure patients: a systematic review and meta-analysis. Lipids Health Dis. 2019;18(1):188. Doi:10.1186/s12944-019-1135-z
92. Singh RR, Slater RE, Wang J, et al. Distinct Mechanisms for Increased Cardiac Contraction Through Selective Alteration of Either Myo¬sin or Troponin Activity. JACC Basic Transl Sci. 2022;7(10):1021-1037. Doi:10.1016/j.jac¬bts.2022.04.013
93. Leancă SA, Afrăsânie I, Crișu D, et al. Cardiac Reverse Remodeling in Ischemic Heart Disease with Novel Therapies for Heart Failure with Reduced Ejection Fraction. Life Basel Switz. 2023;13(4):1000. Doi:10.3390/life13041000
94. Patel PH, Nguyen M, Rodriguez R, Surani S, Udeani G. Omecamtiv Mecarbil: A Novel Mechanistic and Therapeutic Approach to Chronic Heart Failure Management. Cureus. 2021;13(1):e12419. Doi:10.7759/cu-reus.12419
95. Alqatati F, Elbahnasawy M, Bugazia S, et al. Safety and efficacy of omecamtiv mecarbil for heart failure: A systematic review and meta-analysis. Indian Heart J. 2022;74(3):155-162. Doi:10.1016/j.ihj.2022.03.005
96. Zhou S, Liu Y, Huang X, Wu C, Pórszász R. Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future. Front Cardiovasc Med. 2024;11. Doi:10.3389/fcvm.2024.1337154
97. Ibrahim R, Olagunju A, Terrani K, Takamatsu C, Khludenev G, William P. KCCQ total symptom score, clinical outcome measures, and adverse events associated with omecamtiv mecarbil for heart failure with reduced ejection fraction: a systematic review and meta-analysis of ran¬domized controlled trials. Clin Res Cardiol Off J Ger Card Soc. 2023;112(8):1067-1076. Doi:10.1007/s00392-023-02172-w
98. Kalou Y, Al-Khani AM, Haider KH. Bone Mar-row Mesenchymal Stem Cells for Heart Failure Treatment: A Systematic Review and Meta-Analysis. Heart Lung Circ. 2023;32(7):870-880. Doi:10.1016/j.hlc.2023.01.012
99. Shen T, Xia L, Dong W, et al. A Systematic Re-view and Meta-Analysis: Safety and Efficacy of Mesenchymal Stem Cells Therapy for Heart Failure. Curr Stem Cell Res Ther. 2021;16(3):354-365. Doi:10.2174/1574888X15999200820171432
100. Makkar RR, Kereiakes DJ, Aguirre F, et al. In-tracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial. Eur Heart J. 2020;41(36):3451-3458. Doi:10.1093/eurheartj/ehaa541
101. Werb D, Kerr T, Zhang R, Montaner JS, Wood E. Methamphetamine use and malnutrition among street-involved youth. Harm Reduct J. 2010;7:5. Doi:10.1186/1477-7517-7-5
102. Awad AK, Abdelgalil MS, Gonnah AR, et al. Intravenous Iron for Acute and Chronic Heart Failure with Reduced Ejection Fraction (HFrEF) Patients with Iron Deficiency: An Updated Sys¬tematic Review and Meta-Analysis. Clin Med Lond Engl. Published online April 19, 2024:100211. Doi:10.1016/j.clinme.2024.100211
103. Singh RB, Fedacko J, Pella D, et al. High Exog¬enous Antioxidant, Restorative Treatment (Heart) for Prevention of the Six Stages of Heart Failure: The Heart Diet. Antioxid Basel Switz. 2022;11(8):1464. Doi:10.3390/an¬tiox11081464
104. Colin-Ramirez E, Sepehrvand N, Rathwell S, et al. Sodium Restriction in Patients With Heart Failure: A Systematic Review and Meta-Anal¬ysis of Randomized Clinical Trials. Circ Heart Fail. 2023;16(1):e009879. Doi:10.1161/CIR-CHEARTFAILURE.122.009879
105. Liyanage T, Ninomiya T, Wang A, et al. Effects of the Mediterranean Diet on Cardiovascular Outcomes-A Systematic Review and Meta-Analysis. PloS One. 2016;11(8):e0159252. Doi:10.1371/journal.pone.0159252
106. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q₁₀ supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013;97(2):268-275. Doi:10.3945/ajcn.112.040741
107. Lazzarin T, Martins D, Ballarin RS, et al. The Role of Omega-3 in Attenuating Cardiac Re-modeling and Heart Failure through the Oxi-dative Stress and Inflammation Pathways. An-tioxidants. 2023;12(12):2067. Doi:10.3390/antiox12122067
108. Prokopidis K, Therdyothin A, Giannos P, et al. Does omega-3 supplementation improve the inflammatory profile of patients with heart failure? a systematic review and meta-analy-sis. Heart Fail Rev. 2023;28(6):1417-1425. Doi:10.1007/s10741-023-10327-0
109. Masenga SK, Povia JP, Lwiindi PC, Kirabo A. Recent Advances in Microbiota-Associated Metabolites in Heart Failure. Biomedicines. 2023;11(8):2313. Doi:10.3390/biomedi-cines11082313
110. Petruzziello C, Saviano A, Manetti LL, Macer-ola N, Ojetti V. The Role of Gut Microbiota and the Potential Effects of Probiotics in Heart Failure. Med Kaunas Lith. 2024;60(2):271. Doi:10.3390/medicina60020271
111. Pechanova O, Dayar E, Cebova M. Therapeu¬tic Potential of Polyphenols-Loaded Polymeric Nanoparticles in Cardiovascular System. Mol Basel Switz. 2020;25(15):3322. Doi:10.3390/molecules25153322
112. Iqbal I, Wilairatana P, Saqib F, et al. Plant Polyphenols and Their Potential Benefits on Cardiovascular Health: A Review. Mol Basel Switz. 2023;28(17):6403. Doi:10.3390/mol-ecules28176403
113. Mendelson J, Jones RT, Upton R, Jacob P. Methamphetamine and ethanol interactions in humans. Clin Pharmacol Ther. 1995;57(5):559-568. Doi:10.1016/0009-9236(95)90041-1
114. Fleury G, De La Garza R, Mahoney JJ, Evans SE, Newton TF. Predictors of cardiovascular response to methamphetamine administration in methamphetamine-dependent individuals. Am J Addict. 2008;17(2):103-110. Doi:10.1080/10550490701861078
115. de Melo Reis RA, Isaac AR, Freitas HR, et al. Quality of Life and a Surveillant Endocanna-binoid System. Front Neurosci. 2021;15:747229. Doi:10.3389/fnins.2021.747229
116. Razavi Y, Keyhanfar F, Shabani R, Haghparast A, Mehdizadeh M. Therapeutic Effects of Cannabidiol on Methamphetamine Abuse: A Review of Preclinical Study. Iran J Pharm Res IJPR. 2021;20(4):152-164. Doi:10.22037/ijpr.2021.114918.15106
117. Jîtcă G, Ősz BE, Vari CE, Rusz CM, Tero-Vescan A, Pușcaș A. Cannabidiol: Bridge be-tween Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance. An-tioxidants. 2023;12(2):485. Doi:10.3390/an-tiox12020485
118. Nie Q, Dong W, Shen B, et al. Cannabidiol at¬tenuates methamphetamine-induced cardiac inflammatory response through the PKA/CREB pathway in rats. Ann Transl Med. 2022;10(18):985. Doi:10.21037/atm-22-4082
119. Garza-Cervantes JA, Ramos-González M, Lozano O, Jerjes-Sánchez C, García-Rivas G. Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure. Oxid Med Cell Longev. 2020;2020:4587024. Doi:10.1155/2020/4587024
120. Durst R, Danenberg H, Gallily R, et al. Canna¬bidiol, a nonpsychoactive Cannabis constitu¬ent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Physiol. 2007;293(6):H3602-3607. Doi:10.1152/ajpheart.00098.2007
121. Vrajová M, Šlamberová R, Hoschl C, Ovsepian SV. Methamphetamine and sleep impairments: neurobehavioral correlates and molecular mechanisms. Sleep. 2021;44(6):zsab001. Doi:10.1093/sleep/zsab001
122. Zhang C, Chen C, Zhao X, et al. New insight into methamphetamine-associated heart fail-ure revealed by transcriptomic analyses: Cir-cadian rhythm disorder. Toxicol Appl Pharma-col. 2022;451:116172. Doi:10.1016/j.taap.2022.116172
123. Cacciapuoti F, D’Onofrio A, Tarquinio LG, et al. Sleep-disordered breathing and heart fail¬ure: a vicious cycle of cardiovascular risk. Monaldi Arch Chest Dis Arch Monaldi Mal Tor-ace. Published online September 1, 2023. Doi:10.4081/monaldi.2023.2660
124. Costanzo MR, Khayat R, Ponikowski P, et al. Mechanisms and Clinical Consequences of Un-treated Central Sleep Apnea in Heart Failure. J Am Coll Cardiol. 2015;65(1):72-84. Doi:10.1016/j.jacc.2014.10.025
125. Albertsen IE, Bille J, Piazza G, Lip GYH, Niel-sen PB. Cardiovascular Risk in Young Patients Diagnosed With Obstructive Sleep Apnea. J Am Heart Assoc. 2024;13(8):e033506. Doi:10.1161/JAHA.123.033506
126. Chen H, Zhang Q, Hao Y, Zhang J, He Y, Hu K. Cardiac autonomic dysfunction and structural remodeling: the potential mechanism to medi¬ate the relationship between obstructive sleep apnea and cardiac arrhythmias. Front Med. 2024;11:1346400. Doi:10.3389/fmed.2024.1346400
127. Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res. 2016;61(3):253-278. Doi:10.1111/jpi.12360
128. Dzida G, Prystupa A, Lachowska-Kotowska P, et al. Alteration in diurnal and nocturnal mela¬tonin serum level in patients with chronic heart failure. Ann Agric Environ Med AAEM. 2013;20(4):745-748.
129. Reiter RJ, Sharma R, Chuffa LG de A, Simko F, Dominguez-Rodriguez A. Mitochondrial Mela¬tonin: Beneficial Effects in Protecting against Heart Failure. Life Basel Switz. 2024;14(1):88. Doi:10.3390/life14010088
130. Nduhirabandi F, Maarman GJ. Melatonin in Heart Failure: A Promising Therapeutic Strat-egy? Mol Basel Switz. 2018;23(7):1819. Doi:10.3390/molecules23071819
131. Wongprayoon P, Govitrapong P. Melatonin Attenuates Methamphetamine-Induced Neuro¬toxicity. Curr Pharm Des. 2016;22(8):1022-1032. Doi:10.2174/1381612822666151214125657