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Branched-chain amino acids in cardiovascular disease

Nature Reviews Cardiology volume 20, pages 77–89 (2023)Cite this article

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Abstract

Research conducted in the past 15 years has yielded crucial insights that are reshaping our understanding of the systems physiology of branched-chain amino acid (BCAA) metabolism and the molecular mechanisms underlying the close relationship between BCAA homeostasis and cardiovascular health. The rapidly evolving literature paints a complex picture, in which numerous tissue-specific and disease-specific modes of BCAA regulation initiate a diverse set of molecular mechanisms that connect changes in BCAA homeostasis to the pathogenesis of cardiovascular diseases, including myocardial infarction, ischaemia–reperfusion injury, atherosclerosis, hypertension and heart failure. In this Review, we outline the current understanding of the major factors regulating BCAA abundance and metabolic fate, highlight molecular mechanisms connecting impaired BCAA homeostasis to cardiovascular disease, discuss the epidemiological evidence connecting BCAAs with various cardiovascular disease states and identify current knowledge gaps requiring further investigation.

Key points

  • Branched-chain amino acids (BCAAs) — isoleucine, leucine and valine — are essential amino acids that have a crucial role in metabolic homeostasis through nutrient signalling.

  • High circulating concentrations of BCAAs are a hallmark of metabolic disorders, including obesity, insulin resistance and type 2 diabetes mellitus.

  • Mechanisms underlying the association between BCAAs and cardiovascular disease (CVD) are still being defined, but include activation of the serine/threonine protein kinase mTOR, mitochondrial dysfunction, shifts in cardiac substrate utilization and platelet activation.

  • Epidemiological studies have also shown that high plasma BCAA concentrations identify individuals with heart failure, coronary artery disease or hypertension and predict adverse events in these populations.

  • In some other populations (such as African American individuals without CVD and frail elderly individuals), high plasma BCAA concentrations predict improved cardiovascular outcomes.

  • Areas for future research include the roles of tissue-specific BCAA metabolism and inter-organ BCAA metabolic crosstalk in various CVD states and the roles of impaired BCAA metabolism in vascular function and atherosclerosis.

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Fig. 1: Major sources and sites of BCAA supply and utilization.
Fig. 2: Potential mechanisms connecting dysregulated BCAA metabolism with CVD.

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References

  1. Ridaura, V. K. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214 (2013).

    Article  Google Scholar 

  2. Pedersen, H. K. et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376–381 (2016).

    Article  CAS  Google Scholar 

  3. Wolfson, R. L. et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351, 43–48 (2016).

    Article  CAS  Google Scholar 

  4. Felig, P., Marliss, E. & Cahill, G. F. Plasma amino acid levels and insulin secretion in obesity. N. Engl. J. Med. 281, 811–816 (1969).

    Article  CAS  Google Scholar 

  5. White, P. J. & Newgard, C. B. Branched-chain amino acids in disease. Science 363, 582–583 (2019).

    Article  CAS  Google Scholar 

  6. White, P. J. et al. Insulin action, type 2 diabetes, and branched-chain amino acids: a two-way street. Mol. Metab. 52, 101261 (2021).

    Article  CAS  Google Scholar 

  7. Hunter, W. G. et al. Metabolomic profiling identifies novel circulating biomarkers of mitochondrial dysfunction differentially elevated in heart failure with preserved versus reduced ejection fraction: evidence for shared metabolic impairments in clinical heart failure. J. Am. Heart Assoc. 5, e003190 (2016).

    Article  Google Scholar 

  8. Lanfear, D. E. et al. Targeted metabolomic profiling of plasma and survival in heart failure patients. JACC Heart Fail. 5, 823–832 (2017).

    Article  Google Scholar 

  9. Sun, H. et al. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation 133, 2038–2049 (2016).

    Article  CAS  Google Scholar 

  10. Shah, S. H. et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ. Cardiovasc. Genet. 3, 207–214 (2010).

    Article  CAS  Google Scholar 

  11. Bhattacharya, S. et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis 232, 191–196 (2014).

    Article  CAS  Google Scholar 

  12. Flores-Guerrero, J. L. et al. Concentration of branched-chain amino acids is a strong risk marker for incident hypertension. Hypertension 74, 1428–1435 (2019).

    Article  CAS  Google Scholar 

  13. Portero, V. et al. Chronically elevated branched chain amino acid levels are pro-arrhythmic. Cardiovasc. Res. 118, 1742–1757 (2022).

    Article  CAS  Google Scholar 

  14. Jang, C. et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat. Med. 22, 421–426 (2016).

    Article  CAS  Google Scholar 

  15. Green, C. R. et al. Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Nat. Chem. Biol. 12, 15–21 (2016).

    Article  CAS  Google Scholar 

  16. Yoneshiro, T. et al. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature 572, 614–619 (2019).

    Article  CAS  Google Scholar 

  17. Walejko, J. M. et al. Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart. Nat. Commun. 12, 1680 (2021).

    Article  CAS  Google Scholar 

  18. Neinast, M. D. et al. Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab. 29, 417–429.e4 (2019).

    Article  CAS  Google Scholar 

  19. Fillmore, N., Wagg, C. S., Zhang, L., Fukushima, A. & Lopaschuk, G. D. Cardiac branched-chain amino acid oxidation is reduced during insulin resistance in the heart. Am. J. Physiol. Endocrinol. Metab. 315, E1046–E1052 (2018).

    Article  CAS  Google Scholar 

  20. Nishi, K. et al. Branched-chain keto acid inhibits mitochondrial pyruvate carrier and suppresses gluconeogenesis. SSRN Electron. J. https://doi.org/10.2139/ssrn.4022706 (2022).

    Article  Google Scholar 

  21. Li, R. et al. Time series characteristics of serum branched-chain amino acids for early diagnosis of chronic heart failure. J. Proteome Res. 18, 2121–2128 (2019).

    Article  CAS  Google Scholar 

  22. Wang, W. et al. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 311, H1160–H1169 (2016).

    Article  Google Scholar 

  23. Uddin, G. M. et al. Impaired branched chain amino acid oxidation contributes to cardiac insulin resistance in heart failure. Cardiovasc. Diabetol. 18, 86 (2019).

    Article  Google Scholar 

  24. Sansbury, B. E. et al. Metabolomic analysis of pressure-overloaded and infarcted mouse hearts. Circ. Heart Fail. 7, 634–642 (2014).

    Article  CAS  Google Scholar 

  25. Spyropoulos, F. et al. Metabolomic and transcriptomic signatures of chemogenetic heart failure. Am. J. Physiol. Heart Circ. Physiol. 322, H451–H465 (2022).

    Article  CAS  Google Scholar 

  26. Lai, L. et al. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach. Circ. Heart Fail. 7, 1022–1031 (2014).

    Article  CAS  Google Scholar 

  27. Kwon, H. K., Jeong, H., Hwang, D. & Park, Z. Y. Comparative proteomic analysis of mouse models of pathological and physiological cardiac hypertrophy, with selection of biomarkers of pathological hypertrophy by integrative proteogenomics. Biochim. Biophys. acta Proteins Proteom. 1866, 1043–1054 (2018).

    Article  CAS  Google Scholar 

  28. Lu, G. et al. Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. J. Clin. Invest. 119, 1678–1687 (2009).

    Article  CAS  Google Scholar 

  29. Tso, S.-C. et al. Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched-chain α-ketoacid dehydrogenase kinase. J. Biol. Chem. 289, 20583–20593 (2014).

    Article  CAS  Google Scholar 

  30. White, P. J. et al. The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase. Cell Metab. 27, 1281–1293.e7 (2018).

    Article  CAS  Google Scholar 

  31. Chen, M. et al. Therapeutic effect of targeting branched-chain amino acid catabolic flux in pressure-overload induced heart failure. J. Am. Heart Assoc. 8, e011625 (2019).

    Article  CAS  Google Scholar 

  32. Sciarretta, S., Forte, M., Frati, G. & Sadoshima, J. New insights into the role of mTOR signaling in the cardiovascular system. Circ. Res. 122, 489–505 (2018).

    Article  CAS  Google Scholar 

  33. Bueno, O. F. et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 19, 6341–6350 (2000).

    Article  CAS  Google Scholar 

  34. Zhang, L. et al. KLF15 establishes the landscape of diurnal expression in the heart. Cell Rep. 13, 2368–2375 (2015).

    Article  CAS  Google Scholar 

  35. Crnko, S., Du Pré, B. C., Sluijter, J. P. G. & Van Laake, L. W. Circadian rhythms and the molecular clock in cardiovascular biology and disease. Nat. Rev. Cardiol. 16, 437–447 (2019).

    Article  Google Scholar 

  36. McGinnis, G. R. et al. Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart. J. Mol. Cell. Cardiol. 110, 80–95 (2017).

    Article  CAS  Google Scholar 

  37. Latimer, M. N. et al. Branched chain amino acids selectively promote cardiac growth at the end of the awake period. J. Mol. Cell. Cardiol. 157, 31–44 (2021).

    Article  CAS  Google Scholar 

  38. Fan, L., Hsieh, P. N., Sweet, D. R. & Jain, M. K. Krüppel-like factor 15: regulator of BCAA metabolism and circadian protein rhythmicity. Pharmacol. Res. 130, 123–126 (2018).

    Article  CAS  Google Scholar 

  39. Jeyaraj, D. et al. Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature 483, 96–99 (2012).

    Article  CAS  Google Scholar 

  40. Haldar, S. M. et al. Klf15 deficiency is a molecular link between heart failure and aortic aneurysm formation. Sci. Transl. Med. 2, 26ra26 (2010).

    Article  Google Scholar 

  41. Prosdocimo, D. A. et al. Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism. J. Biol. Chem. 289, 5914–5924 (2014).

    Article  CAS  Google Scholar 

  42. Lu, G. et al. A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Genes Dev. 21, 784–796 (2007).

    Article  CAS  Google Scholar 

  43. Doehner, W., Frenneaux, M. & Anker, S. D. Metabolic impairment in heart failure: the myocardial and systemic perspective. J. Am. Coll. Cardiol. 64, 1388–1400 (2014).

    Article  Google Scholar 

  44. Murashige, D. et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 370, 364–368 (2020).

    Article  CAS  Google Scholar 

  45. White, P. J. et al. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export. Mol. Metab. 5, 538–551 (2016).

    Article  CAS  Google Scholar 

  46. McGarrah, R. W. et al. Dietary branched-chain amino acid restriction alters fuel selection and reduces triglyceride stores in hearts of Zucker fatty rats. Am. J. Physiol. Endocrinol. Metab. 318, E216–E223 (2020).

    Article  CAS  Google Scholar 

  47. Shao, D. et al. Glucose promotes cell growth by suppressing branched-chain amino acid degradation. Nat. Commun. 9, 2935 (2018).

    Article  Google Scholar 

  48. Zhou, Y., Jetton, T. L., Goshorn, S., Lynch, C. J. & She, P. Transamination is required for α-ketoisocaproate but not leucine to stimulate insulin secretion. J. Biol. Chem. 285, 33718–33726 (2010).

    Article  CAS  Google Scholar 

  49. Uddin, G. M. et al. Deletion of BCATm increases insulin-stimulated glucose oxidation in the heart. Metabolism 124, 154871 (2021).

    Article  CAS  Google Scholar 

  50. Raffel, S. et al. BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation. Nature 551, 384–388 (2017).

    Article  CAS  Google Scholar 

  51. Leenders, J. J. et al. Regulation of cardiac gene expression by KLF15, a repressor of myocardin activity. J. Biol. Chem. 285, 27449–27456 (2010).

    Article  CAS  Google Scholar 

  52. Grajeda-Iglesias, C., Rom, O. & Aviram, M. Branched-chain amino acids and atherosclerosis: friends or foes? Curr. Opin. Lipidol. 29, 166–169 (2018).

    Article  CAS  Google Scholar 

  53. Zhao, Y. et al. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice. Acta Pharmacol. Sin. 37, 196–203 (2016).

    Article  CAS  Google Scholar 

  54. Rom, O. et al. Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice: a key role for triglyceride metabolism. J. Nutr. Biochem. 45, 24–38 (2017).

    Article  CAS  Google Scholar 

  55. Wu, G. et al. Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J. Nutr. 137, 2680–2685 (2007).

    Article  CAS  Google Scholar 

  56. Kakoki, M. et al. Amino acids as modulators of endothelium-derived nitric oxide. Am. J. Physiol. Ren. Physiol. 291, F297–F304 (2006).

    Article  CAS  Google Scholar 

  57. Schachter, D. & Sang, J. C. Aortic leucine-to-glutamate pathway: metabolic route and regulation of contractile responses. Am. J. Physiol. Heart Circ. Physiol. 282, H1135–H1148 (2002).

    Article  CAS  Google Scholar 

  58. Reho, J. J., Guo, D. F. & Rahmouni, K. Mechanistic target of rapamycin complex 1 signaling modulates vascular endothelial function through reactive oxygen species. J. Am. Heart Assoc. 8, e010662 (2019).

    Article  Google Scholar 

  59. Zhenyukh, O. et al. Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation. J. Cell. Mol. Med. 22, 4948–4962 (2018).

    Article  CAS  Google Scholar 

  60. Xu, Y. et al. Branched-chain amino acid catabolism promotes thrombosis risk by enhancing tropomodulin-3 propionylation in platelets. Circulation 142, 49–64 (2020).

    Article  CAS  Google Scholar 

  61. Li, T. et al. Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury. Cell Metab. 25, 374–385 (2017).

    Article  CAS  Google Scholar 

  62. Lian, K. et al. PP2Cm overexpression alleviates MI/R injury mediated by a BCAA catabolism defect and oxidative stress in diabetic mice. Eur. J. Pharmacol. 866, 172796 (2020).

    Article  CAS  Google Scholar 

  63. Adabag, A. S., Luepker, R. V., Roger, V. L. & Gersh, B. J. Sudden cardiac death: epidemiology and risk factors. Nat. Rev. Cardiol. 7, 216–225 (2010).

    Article  Google Scholar 

  64. Fontana, L., Partridge, L. & Longo, V. D. Extending healthy life span–from yeast to humans. Science 328, 321–326 (2010).

    Article  CAS  Google Scholar 

  65. Le Couteur, D. G. et al. Branched chain amino acids, aging and age-related health. Ageing Res. Rev. 64, 101198 (2020).

    Article  Google Scholar 

  66. Green, C. L. et al. The effects of graded levels of calorie restriction: XIII. Global metabolomics screen reveals graded changes in circulating amino acids, vitamins, and bile acids in the plasma of C57BL/6 mice. J. Gerontol. A Biol. Sci. Med. Sci. 74, 16–26 (2019).

    CAS  Google Scholar 

  67. Solon-Biet, S. M. et al. Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control. Nat. Metab. 1, 532–545 (2019).

    Article  CAS  Google Scholar 

  68. Richardson, N. E. et al. Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice. Nat. Aging 1, 73–86 (2021).

    Article  Google Scholar 

  69. Du, X. et al. Increased branched-chain amino acid levels are associated with long-term adverse cardiovascular events in patients with STEMI and acute heart failure. Life Sci. 209, 167–172 (2018).

    Article  CAS  Google Scholar 

  70. Ahmad, T. et al. Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support. J. Am. Coll. Cardiol. 67, 291–299 (2016).

    Article  CAS  Google Scholar 

  71. Lim, L. L. et al. Circulating branched-chain amino acids and incident heart failure in type 2 diabetes: the Hong Kong diabetes register. Diabetes Metab. Res. Rev. 36, e3253 (2020).

    Article  CAS  Google Scholar 

  72. Nemutlu, E. et al. Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure. J. Card. Fail. 21, 460–469 (2015).

    Article  Google Scholar 

  73. Zhang, Z. Y. et al. Diastolic left ventricular function in relation to circulating metabolic biomarkers in a population study. Eur. J. Prev. Cardiol. 26, 22–32 (2019).

    Article  Google Scholar 

  74. Shah, S. H. et al. Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease. Am. Heart J. 163, 844–850.e1 (2012).

    Article  CAS  Google Scholar 

  75. Du, X. et al. Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI. Sci. Rep. 8, 15809 (2018).

    Article  Google Scholar 

  76. Ruiz-Canela, M. et al. Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial. Clin. Chem. 62, 582–592 (2016).

    Article  CAS  Google Scholar 

  77. Magnusson, M. et al. A diabetes-predictive amino acid score and future cardiovascular disease. Eur. Heart J. 34, 1982–1989 (2013).

    Article  CAS  Google Scholar 

  78. Tobias, D. K. et al. Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ. Genom. Precis. Med. 11, e002157 (2018).

    Article  CAS  Google Scholar 

  79. Chevli, P. A. et al. Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study. Cardiovasc. Diabetol. 20, 231 (2021).

    Article  CAS  Google Scholar 

  80. Cruz, D. E. et al. Metabolomic analysis of coronary heart disease in an African American cohort from the Jackson Heart Study. JAMA Cardiol. 7, 184–194 (2022).

    Article  Google Scholar 

  81. Yamaguchi, N. et al. Plasma free amino acid profiles evaluate risk of metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large Asian population. Environ. Health Prev. Med. 22, 35 (2017).

    Article  Google Scholar 

  82. Yang, R. et al. Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors. PLoS ONE 9, e99598 (2014).

    Article  Google Scholar 

  83. Teymoori, F., Asghari, G., Mirmiran, P. & Azizi, F. Dietary amino acids and incidence of hypertension: a principle component analysis approach. Sci. Rep. 7, 16838 (2017).

    Article  Google Scholar 

  84. Jennings, A. et al. Amino acid intakes are inversely associated with arterial stiffness and central blood pressure in women. J. Nutr. 145, 2130–2138 (2015).

    Article  CAS  Google Scholar 

  85. Kimberly, W. T., Wang, Y., Pham, L., Furie, K. L. & Gerszten, R. E. Metabolite profiling identifies a branched chain amino acid signature in acute cardioembolic stroke. Stroke 44, 1389–1395 (2013).

    Article  CAS  Google Scholar 

  86. Le Couteur, D. G. et al. Branched chain amino acids, cardiometabolic risk factors and outcomes in older men: the Concord Health and Ageing in Men Project. J. Gerontol. A Biol. Sci. Med. Sci. 75, 1805–1810 (2020).

    Article  Google Scholar 

  87. Lerman, J. B. et al. Plasma metabolites associated with functional and clinical outcomes in heart failure with reduced ejection fraction with and without type 2 diabetes. Sci. Rep. 12, 9183 (2022).

    Article  CAS  Google Scholar 

  88. Tsuji, S. et al. Nutritional status of outpatients with chronic stable heart failure based on serum amino acid concentration. J. Cardiol. 72, 458–465 (2018).

    Article  Google Scholar 

  89. Blackburn, P. R. et al. Maple syrup urine disease: mechanisms and management. Appl. Clin. Genet. 10, 57–66 (2017).

    Article  CAS  Google Scholar 

  90. Fontana, L. et al. Decreased consumption of branched-chain amino acids improves metabolic health. Cell Rep. 16, 520–530 (2016).

    Article  CAS  Google Scholar 

  91. Tuchman, M. et al. Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Mol. Genet. Metab. 94, 397–402 (2008).

    Article  CAS  Google Scholar 

  92. Brunetti-Pierri, N. et al. Phenylbutyrate therapy for maple syrup urine disease. Hum. Mol. Genet. 20, 631–640 (2011).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are supported by NIH grants K08HL135275 (R.W.M.) and R01HL160689 (R.W.M.), American Diabetes Association Pathway to Stop Diabetes Award 1-16-INI-17 (P.J.W.), the Edna and Fred L. Mandel Jr. Foundation (R.W.M.) and the Duke School of Medicine Strong Start Award (R.W.M.).

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Authors and Affiliations

  1. Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA

    Robert W. McGarrah & Phillip J. White

  2. Sarah W. Stedman Nutrition and Metabolism Center, Duke University School of Medicine, Durham, NC, USA

    Robert W. McGarrah

  3. Department of Medicine, Division of Cardiology, Duke University, Durham, NC, USA

    Robert W. McGarrah

  4. Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University, Durham, NC, USA

    Phillip J. White

  5. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA

    Phillip J. White

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McGarrah, R.W., White, P.J. Branched-chain amino acids in cardiovascular disease. Nat Rev Cardiol 20, 77–89 (2023). https://doi.org/10.1038/s41569-022-00760-3

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