The Association between Vitamin D Levels and Thrombus Burden in Patients with ST-Elevation Myocardial Infarction
Abstract
Background: In current practice, establishing the potential predictors of high thrombus burden (HTB) before primary percutaneous coronary intervention (PCI) is crucial for its management. In this research, we aimed to investigate the association between vitamin D levels and HTB in patients with ST-elevation myocardial infarction (STEMI).
Methods: This prospective, observational study was conducted on 257 STEMI patients undergoing primary PCI in Van Education and Research Hospital between March 2020 and March 2021. The thrombus burden grade was determined for each subject. The study population was divided into 2 groups: patients with HTB and those with low thrombus burden (LTB) based on the thrombus burden grade. Demographic, laboratory, and angiographic features were compared between the groups.
Results: In total, 154 patients (mean age±SD=63.42±11.53 y, 65.6% male) had HTB and 103 patients had LTB (mean age±SD=61.50±10.23 y, 70.9% male). The patients stratified into the HTB group had lower vitamin D levels than those in the LTB group (8.0 ng/mL vs 17.9 ng/mL, respectively; P<0.001). The patients with HTB and low vitamin D levels had lower post-PCI thrombolysis in myocardial infarction (TIMI) flow, TIMI myocardial perfusion grade, and post-PCI ST resolution. In a multivariable analysis, vitamin D was an independent predictor of HTB among the STEMI patients (OR: 0.76, 95%CI: 0.70–0.82; P<0.001). The ideal value of vitamin D to predict HTB was >17.6 ng/mL with a sensitivity of 81.8% and a specificity of 90.3%.
Conclusion: The study results showed that vitamin D levels were an independent predictor of HTB in STEMI patients treated by primary PCI.
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2. Karur S, Veerappa V, Nanjappa MC. Study of vitamin D deficiency prevalence in acute myocardial infarction. Int J Cardiol Heart Vessel 2014;3:57-59.
3. Ismail HM, Algrafi AS, Amoudi O, Ahmed S, Al-Thagfan SS, Shora H, Aljohani M, Almutairi M, Alharbi F, Alhejaili A, Alamri M, Muhawish A, Abdallah A. Vitamin D and its metabolites deficiency in acute coronary syndrome patients undergoing coronary angiography: a case-control study. Vasc Health Risk Manag 2021;17:471-480.
4. Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YC. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 2005;288:E125-132.
5. Bernini G, Carrara D, Bacca A, Carli V, Virdis A, Rugani I, Duranti E, Ghiadoni L, Bernini M, Taddei S. Effect of acute and chronic vitamin D administration on systemic renin angiotensin system in essential hypertensives and controls. J Endocrinol Invest 2013;36:216-220.
6. Zhang JY, Wu P, Chen D, Ning F, Lu Q, Qiu X, Hewison M, Tamblyn JA, Kilby MD, Lash GE. Vitamin D promotes trophoblast cell induced separation of vascular smooth muscle cells in vascular remodeling via induction of G-CSF. Front Cell Dev Biol 2020;8:601043.
7. Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D's effect on immune function. Nutrients 2020;12:1248.
8. Surdu AM, Pînzariu O, Ciobanu DM, Negru AG, Căinap SS, Lazea C, Iacob D, Săraci G, Tirinescu D, Borda IM, Cismaru G. Vitamin D and its role in the lipid metabolism and the development of atherosclerosis. Biomedicines 2021;9:172.
9. Siasos G, Tousoulis D, Oikonomou E, Maniatis K, Kioufis S, Kokkou E, Vavuranakis M, Zaromitidou M, Kassi E, Miliou A, Stefanadis C. Vitamin D3, D2 and arterial wall properties in coronary artery disease. Curr Pharm Des 2014;20:5914-5918.
10. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-177.
11. Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT, Michalis LK, Serruys PW. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol 2007;50:573-583.
12. Sianos G, Papafaklis MI, Serruys PW. Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J Invasive Cardiol 2010;22:6B-14B.
13. Scarparo P, van Gameren M, Wilschut J, Daemen J, Den Dekker WK, De Jaegere P, Zijlstra F, Van Mieghem NM, Diletti R. Impact of large thrombus burden on very long-term clinical outcomes in patients presenting with ST-segment elevation myocardial infarction. J Invasive Cardiol 2021;33:E900-E909.
14. Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E; TIMI Study Group. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation 2001;103:2550-2554.
15. Burzotta F, Trani C, Romagnoli E, Belloni F, Biondi-Zoccai GG, Mazzari MA, De Vita M, Giannico F, Garramone B, Niccoli G, Rebuzzi AG, Mongiardo R, Schiavoni G, Crea F. A pilot study with a new, rapid-exchange, thrombus-aspirating device in patients with thrombus-containing lesions: the Diver C.E. study. Catheter Cardiovasc Interv 2006;67:887-893.
16. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987;76:142-154.
17. Henriques JP, Zijlstra F, van 't Hof AW, de Boer MJ, Dambrink JH, Gosselink M, Hoorntje JC, Suryapranata H. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation 2003;107:2115-2119.
18. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; ESC Scientific Document Group. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237-269.
19. Sánchez-Recalde A, Merino JL, Moreno R, Jiménez-Valero S, Galeote G, Calvo L, López de Sá E, López-Sendón JL. Clinical implications of intracoronary findings beyond coronary angiograms in patients with sudden death and high probability of coronary artery disease. Rev Esp Cardiol 2011;64:819-823.
20. Knuschke P. Sun exposure and vitamin D. Curr Probl Dermatol 2021;55:296-315.
21. Jorde R, Haug E, Figenschau Y, Hansen JB. Serum levels of vitamin D and haemostatic factors in healthy subjects: the Tromsø study. Acta Haematol 2007;117:91-97.
22. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 2016;96:365-408.
23. Latic N, Erben RG. Vitamin D and cardiovascular disease, with emphasis on hypertension, atherosclerosis, and heart failure. Int J Mol Sci 2020;21:6483.
24. Wu WX, He DR. Low vitamin D levels are associated with the development of deep venous thromboembolic events in patients with ischemic stroke. Clin Appl Thromb Hemost 2018;24:69S-75S.
25. Korzonek-Szlacheta I, Hudzik B, Nowak J, Szkodzinski J, Nowak J, Gąsior M, Zubelewicz-Szkodzinska B. Mean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patients with stable coronary artery disease. Heart Vessels 2018;33:1275-1281.
26. García-Carrasco M, Jiménez-Herrera EA, Gálvez-Romero JL, Mendoza-Pinto C, Méndez-Martínez S, Etchegaray-Morales I, Munguía-Realpozo P, Vázquez de Lara-Cisneros L, Santa Cruz FJ, Cervera R. The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome. Lupus 2018;27:2181-2189.
27. Aihara K, Azuma H, Akaike M, Ikeda Y, Yamashita M, Sudo T, Hayashi H, Yamada Y, Endoh F, Fujimura M, Yoshida T, Yamaguchi H, Hashizume S, Kato M, Yoshimura K, Yamamoto Y, Kato S, Matsumoto T. Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem 2004;279:35798-35802.
28. Owens AP, 3rd, Mackman N. Role of tissue factor in atherothrombosis. Curr Atheroscler Rep 2012;14:394-401.
29. Bouillon R. Vitamin D and cardiovascular disorders. Osteoporos Int 2019;30:2167-2181.
30. Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study, Tromsø, Norway. J Thromb Haemost 2010;8:157-162.
31. Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C. 1,25(OH)2 vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation 2009;120:687-698.
32. Zittermann A, Gummert JF, Börgermann J. The role of vitamin D in dyslipidemia and cardiovascular disease. Curr Pharm Des 2011;17:933-942.
33. Roquer J, Segura T, Serena J, Castillo J. Endothelial dysfunction, vascular disease and stroke: the ARTICO study. Cerebrovasc Dis 2009;27:25-37.
34. Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008;25:320-325.
35. Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 2009;94:4023-4030.
36. Syal SK, Kapoor A, Bhatia E, Sinha A, Kumar S, Tewari S, Garg N, Goel PK. Vitamin D deficiency, coronary artery disease, and endothelial dysfunction: observations from a coronary angiographic study in Indian patients. J Invasive Cardiol 2012;24:385-389.
37. Roy A, Lakshmy R, Tarik M, Tandon N, Reddy KS, Prabhakaran D. Independent association of severe vitamin D deficiency as a risk of acute myocardial infarction in Indians. Indian Heart J 2015;67:27-32.
38. Machulsky NF, Barchuk M, Gagliardi J, Gonzalez D, Lombardo M, Escudero AG, Gigena G, Blanco F, Schreier L, Fabre B, Berg G. Vitamin D is related to markers of vulnerable plaque in acute myocardial infarction. Curr Vasc Pharmacol 2018;16:355-360.
39. Milazzo V, De Metrio M, Cosentino N, Marenzi G, Tremoli E. Vitamin D and acute myocardial infarction. World J Cardiol 2017;9:14-20.
40. Şen Ö, Şen SB, Topuz AN, Topuz M. Vitamin D level predicts angiographic no-reflow phenomenon after percutaneous coronary intervention in patients with ST segment elevation myocardial infarction. Biomark Med 2021;15:1357-1366.
41. Abdallah AA, Elrhman MAA, Elshazly A, Bastawy I. Relationship of serum vitamin D levels with coronary thrombus grade, TIMI flow, and myocardial blush grade in patients with acute ST-segment elevation myocardial infarction. Egypt Heart J 2020;72:84.
2. Karur S, Veerappa V, Nanjappa MC. Study of vitamin D deficiency prevalence in acute myocardial infarction. Int J Cardiol Heart Vessel 2014;3:57-59.
3. Ismail HM, Algrafi AS, Amoudi O, Ahmed S, Al-Thagfan SS, Shora H, Aljohani M, Almutairi M, Alharbi F, Alhejaili A, Alamri M, Muhawish A, Abdallah A. Vitamin D and its metabolites deficiency in acute coronary syndrome patients undergoing coronary angiography: a case-control study. Vasc Health Risk Manag 2021;17:471-480.
4. Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YC. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 2005;288:E125-132.
5. Bernini G, Carrara D, Bacca A, Carli V, Virdis A, Rugani I, Duranti E, Ghiadoni L, Bernini M, Taddei S. Effect of acute and chronic vitamin D administration on systemic renin angiotensin system in essential hypertensives and controls. J Endocrinol Invest 2013;36:216-220.
6. Zhang JY, Wu P, Chen D, Ning F, Lu Q, Qiu X, Hewison M, Tamblyn JA, Kilby MD, Lash GE. Vitamin D promotes trophoblast cell induced separation of vascular smooth muscle cells in vascular remodeling via induction of G-CSF. Front Cell Dev Biol 2020;8:601043.
7. Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D's effect on immune function. Nutrients 2020;12:1248.
8. Surdu AM, Pînzariu O, Ciobanu DM, Negru AG, Căinap SS, Lazea C, Iacob D, Săraci G, Tirinescu D, Borda IM, Cismaru G. Vitamin D and its role in the lipid metabolism and the development of atherosclerosis. Biomedicines 2021;9:172.
9. Siasos G, Tousoulis D, Oikonomou E, Maniatis K, Kioufis S, Kokkou E, Vavuranakis M, Zaromitidou M, Kassi E, Miliou A, Stefanadis C. Vitamin D3, D2 and arterial wall properties in coronary artery disease. Curr Pharm Des 2014;20:5914-5918.
10. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-177.
11. Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT, Michalis LK, Serruys PW. Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol 2007;50:573-583.
12. Sianos G, Papafaklis MI, Serruys PW. Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J Invasive Cardiol 2010;22:6B-14B.
13. Scarparo P, van Gameren M, Wilschut J, Daemen J, Den Dekker WK, De Jaegere P, Zijlstra F, Van Mieghem NM, Diletti R. Impact of large thrombus burden on very long-term clinical outcomes in patients presenting with ST-segment elevation myocardial infarction. J Invasive Cardiol 2021;33:E900-E909.
14. Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E; TIMI Study Group. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation 2001;103:2550-2554.
15. Burzotta F, Trani C, Romagnoli E, Belloni F, Biondi-Zoccai GG, Mazzari MA, De Vita M, Giannico F, Garramone B, Niccoli G, Rebuzzi AG, Mongiardo R, Schiavoni G, Crea F. A pilot study with a new, rapid-exchange, thrombus-aspirating device in patients with thrombus-containing lesions: the Diver C.E. study. Catheter Cardiovasc Interv 2006;67:887-893.
16. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987;76:142-154.
17. Henriques JP, Zijlstra F, van 't Hof AW, de Boer MJ, Dambrink JH, Gosselink M, Hoorntje JC, Suryapranata H. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation 2003;107:2115-2119.
18. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; ESC Scientific Document Group. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019;40:237-269.
19. Sánchez-Recalde A, Merino JL, Moreno R, Jiménez-Valero S, Galeote G, Calvo L, López de Sá E, López-Sendón JL. Clinical implications of intracoronary findings beyond coronary angiograms in patients with sudden death and high probability of coronary artery disease. Rev Esp Cardiol 2011;64:819-823.
20. Knuschke P. Sun exposure and vitamin D. Curr Probl Dermatol 2021;55:296-315.
21. Jorde R, Haug E, Figenschau Y, Hansen JB. Serum levels of vitamin D and haemostatic factors in healthy subjects: the Tromsø study. Acta Haematol 2007;117:91-97.
22. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 2016;96:365-408.
23. Latic N, Erben RG. Vitamin D and cardiovascular disease, with emphasis on hypertension, atherosclerosis, and heart failure. Int J Mol Sci 2020;21:6483.
24. Wu WX, He DR. Low vitamin D levels are associated with the development of deep venous thromboembolic events in patients with ischemic stroke. Clin Appl Thromb Hemost 2018;24:69S-75S.
25. Korzonek-Szlacheta I, Hudzik B, Nowak J, Szkodzinski J, Nowak J, Gąsior M, Zubelewicz-Szkodzinska B. Mean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patients with stable coronary artery disease. Heart Vessels 2018;33:1275-1281.
26. García-Carrasco M, Jiménez-Herrera EA, Gálvez-Romero JL, Mendoza-Pinto C, Méndez-Martínez S, Etchegaray-Morales I, Munguía-Realpozo P, Vázquez de Lara-Cisneros L, Santa Cruz FJ, Cervera R. The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome. Lupus 2018;27:2181-2189.
27. Aihara K, Azuma H, Akaike M, Ikeda Y, Yamashita M, Sudo T, Hayashi H, Yamada Y, Endoh F, Fujimura M, Yoshida T, Yamaguchi H, Hashizume S, Kato M, Yoshimura K, Yamamoto Y, Kato S, Matsumoto T. Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem 2004;279:35798-35802.
28. Owens AP, 3rd, Mackman N. Role of tissue factor in atherothrombosis. Curr Atheroscler Rep 2012;14:394-401.
29. Bouillon R. Vitamin D and cardiovascular disorders. Osteoporos Int 2019;30:2167-2181.
30. Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study, Tromsø, Norway. J Thromb Haemost 2010;8:157-162.
31. Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C. 1,25(OH)2 vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation 2009;120:687-698.
32. Zittermann A, Gummert JF, Börgermann J. The role of vitamin D in dyslipidemia and cardiovascular disease. Curr Pharm Des 2011;17:933-942.
33. Roquer J, Segura T, Serena J, Castillo J. Endothelial dysfunction, vascular disease and stroke: the ARTICO study. Cerebrovasc Dis 2009;27:25-37.
34. Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008;25:320-325.
35. Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 2009;94:4023-4030.
36. Syal SK, Kapoor A, Bhatia E, Sinha A, Kumar S, Tewari S, Garg N, Goel PK. Vitamin D deficiency, coronary artery disease, and endothelial dysfunction: observations from a coronary angiographic study in Indian patients. J Invasive Cardiol 2012;24:385-389.
37. Roy A, Lakshmy R, Tarik M, Tandon N, Reddy KS, Prabhakaran D. Independent association of severe vitamin D deficiency as a risk of acute myocardial infarction in Indians. Indian Heart J 2015;67:27-32.
38. Machulsky NF, Barchuk M, Gagliardi J, Gonzalez D, Lombardo M, Escudero AG, Gigena G, Blanco F, Schreier L, Fabre B, Berg G. Vitamin D is related to markers of vulnerable plaque in acute myocardial infarction. Curr Vasc Pharmacol 2018;16:355-360.
39. Milazzo V, De Metrio M, Cosentino N, Marenzi G, Tremoli E. Vitamin D and acute myocardial infarction. World J Cardiol 2017;9:14-20.
40. Şen Ö, Şen SB, Topuz AN, Topuz M. Vitamin D level predicts angiographic no-reflow phenomenon after percutaneous coronary intervention in patients with ST segment elevation myocardial infarction. Biomark Med 2021;15:1357-1366.
41. Abdallah AA, Elrhman MAA, Elshazly A, Bastawy I. Relationship of serum vitamin D levels with coronary thrombus grade, TIMI flow, and myocardial blush grade in patients with acute ST-segment elevation myocardial infarction. Egypt Heart J 2020;72:84.
| Files | ||
| Issue | Vol 17 No 2 (2022): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v17i2.9835 | |
| Keywords | ||
| Coronary thrombosis Vitamin D ST elevation myocardial infarction | ||
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How to Cite
1.
Şaylık F, Selçuk M, Akbulut T, Çınar T. The Association between Vitamin D Levels and Thrombus Burden in Patients with ST-Elevation Myocardial Infarction. J Tehran Heart Cent. 2022;17(2):48-55.
