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Transient stress-related hyperviscosity and endothelial dysfunction in Takotsubo syndrome: a time course study

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Abstract

Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome, frequently associated with emotional or physical stress. Its pathophysiology remains largely unclear, although several mechanisms related to catecholaminergic storm have been proposed. In this study we analyzed during the acute phase of TTS and at follow-up both hemorheological parameters and biomarkers of endothelial damage, whose time course has never been fully explored. In 50 TTS women, we analyzed several hemorheological parameters [whole blood viscosity (WBV) at 0.512 s−1 and at 94.5 s−1, plasma viscosity (PLV), erythrocyte deformability and aggregation index] as well as biomarkers of endothelial dysfunction [von Willebrand Factor (vWF), Plasminogen activator inhibitor-1 and factor VIII levels] during the acute phase and after a median 6 months follow-up. These variables were also assessed in 50 age-matched healthy women. Respect to follow-up, in the acute phase of TTS we observed higher values of white blood cell count, fibrinogen, WBV at low and high shear rates, PLV, erythrocyte aggregation index and lower values of erythrocyte elongation index. Moreover, all biomarkers of endothelial dysfunction resulted significantly higher in the acute phase. During follow-up WBV at 94.5 s−1, erythrocyte elongation index and vWF resulted significantly altered with respect to controls. The results of this study confirm the role of hyperviscosity and endothelial dysfunction in TTS pathophysiology. Moreover, they suggest the persistence of alterations of erythrocyte deformability and endothelial dysfunction even beyond the acute phase that could be the target of therapeutic strategies also during follow-up.

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References

  1. Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, Sheppard MN, Figtree GA, Parodi G, Ruschitzka F, Filippatos G, Mebazaa A, Omerovic E (2016) Current state of knowledge on Takotsubo syndrome and other acute reversible stress-induced heart failure syndromes: a position statement from the taskforce on Takotsubo syndrome of the heart failure association of the European Society of Cardiology. Eur J Heart Fail 18:8–27

    Article  PubMed  Google Scholar 

  2. Ghadri JR, Cammann VL, Napp LC, Jurisic S, Diekmann J, Bataiosu DR, Seifert B, Jaguszewski M, Sarcon A, Neumann CA, Geyer V, Prasad A, Bax JJ, Ruschitzka F, Luscher TF, Templin C (2016) International Takotsubo registry. Differences in the clinical profile and outcomes of typical and atypical Takotsubo syndrome: data from the international Takotsubo registry. JAMA Cardiol 1:335–340

    Article  PubMed  Google Scholar 

  3. Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y-Hassan S, Migliore F, Horowitz JD, Shimokawa H, Lüscher TF, Templin C (2018) International expert consensus document on Takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 39:2032–2046

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sato H (1990) Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm. In: Kodama K, Hori HM (eds) clinical aspect of myocardial injury: from ischemia to heart failure. Kagakuhyoronsha Publishing Co, Tokyo, pp 56–64

    Google Scholar 

  5. Desmet WJ, Adriaenssens BF, Dens JA (2003) Apical ballooning of the left ventricle: first series in white patients. Heart 89:1027–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kurisu S, Kihara Y (2012) Tako-tsubo cardiomyopathy: clinical presentation and underlying mechanism. J Cardiol 60:429–437

    Article  PubMed  Google Scholar 

  7. Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, Kono Y, Umemura T, Nakamura S (2002) Takotsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 143:448–455

    Article  PubMed  Google Scholar 

  8. Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I (2001) Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina pectoris-myocardial infarction investigations in Japan. J Am Coll Cardiol 38:11–18

    Article  CAS  PubMed  Google Scholar 

  9. Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschöpe C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Böhm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Lüscher TF (2015) Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med 373:929–938

    Article  CAS  PubMed  Google Scholar 

  10. Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC (2005) Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 352:539–548

    Article  CAS  PubMed  Google Scholar 

  11. Kume T, Kawamoto T, Okura H, Toyota E, Neishi Y, Watanabe N, Hayashida A, Okahashi N, Yoshimura Y, Saito K, Nezuo S, Yamada R, Yoshida K (2008) Local release of catecholamines from the hearts of patients with Tako-tsubo-like left ventricular dysfunction. Circ J 72:106–108

    Article  CAS  PubMed  Google Scholar 

  12. Galiuto L, De Caterina AR, Porfidia A, Paraggio L, Barchetta S, Locorotondo G, Rebuzzi AG, Crea F (2010) Reversible coronary microvascular dysfunction: a common pathogenetic mechanism in apical ballooning or Tako-tsubo syndrome. Eur Heart J 31:1319–1327

    Article  PubMed  Google Scholar 

  13. Uchida Y, Egami H, Uchida Y, Sakurai T, Kanai M, Shirai S, Nakagawa O, Oshima T (2010) Possible participation of endothelial cell apoptosis of coronary microvessels in the genesis of Takotsubo cardiomyopathy. Clin Cardiol 33:371–377

    Article  PubMed  PubMed Central  Google Scholar 

  14. Barletta G, Del Pace S, Boddi M, Del Bene R, Salvadori C, Bellandi B, Coppo M, Saletti E, Gensini GF (2009) Abnormal coronary reserve and left ventricular wall motion during cold pressor test in patients with previous left ventricular ballooning syndrome. Eur Heart J 30:3007–3014

    Article  PubMed  Google Scholar 

  15. Patel SM, Lerman A, Lennon RJ, Prasad A (2013) Impaired coronary microvascular reactivity in women with apical ballooning syndrome (Takotsubo/stress cardiomyopathy). Eur Heart J Acute Cardiovasc Care 2:147–152

    Article  PubMed  PubMed Central  Google Scholar 

  16. Naegele M, Flammer AJ, Enseleit F, Roas S, Frank M, Hirt A, Kaiser P, Cantatore S, Templin C, Fröhlich G, Romanens M, Lüscher TF, Ruschitzka F, Noll G, Sudano I (2016) Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome. Int J Cardiol 224:226–230

    Article  CAS  PubMed  Google Scholar 

  17. Amadio P, Porro B, Cavalca V, Barbieri SS, Eligini S, Fiorelli S, Di Minno A, Gorini A, Giuliani M, Werba JP, Cosentino N, Olivares P, Barbieri S, Veglia F, Tremoli E, Trabattoni D (2021) Persistent long-term platelet activation and endothelial perturbation in women with Takotsubo syndrome. Biomed Pharmacother 136:111259

    Article  CAS  PubMed  Google Scholar 

  18. El-Battrawy I, Borggrefe M, Akin I (2017) Endothelial dysfunction in Takotsubo syndrome. Int J Cardiol 234:101

    Article  PubMed  Google Scholar 

  19. Carbonara R, Giardinelli F, Pepe M, Luzzi G, Panettieri I, Vulpis V, Bortone AS, Ciccone MM (2018) Correlation between endothelial dysfunction and myocardial damage in acute phase of Tako-Tsubo cardiomyopathy: brachial flow mediated dilation as a potential marker for assessment of patient with Tako-Tsubo. Heart Vessels 33:291–298

    Article  PubMed  Google Scholar 

  20. Verna E, Provasoli S, Ghiringhelli S, Morandi F, Salerno-Uriarte J (2018) Abnormal coronary vasoreactivity in transient left ventricular apical ballooning (Tako-tsubo) syndrome. Int J Cardiol 250:4–10

    Article  PubMed  Google Scholar 

  21. Wilson HM, Cheyne L, Brown PAJ, Kerr K, Hannah A, Srinivasan J, Duniak N, Horgan G, Dawson DK (2018) Characterization of the myocardial inflammatory response in acute stress-induced (Takotsubo) cardiomyopathy. JACC Basic Transl Sci 3:766–778

    Article  PubMed  PubMed Central  Google Scholar 

  22. Scally C, Abbas H, Ahearn T, Srinivasan J, Mezincescu A, Rudd A, Spath N, Yucel-Finn A, Yuecel R, Oldroyd K, Dospinescu C, Horgan G, Broadhurst P, Henning A, Newby DE, Semple S, Wilson HM, Dawson DK (2019) Myocardial and systemic inflammation in acute stress-induced (Takotsubo) cardiomyopathy. Circulation 139:1581–1592

    Article  PubMed  PubMed Central  Google Scholar 

  23. Parkkonen O, Mustonen P, Puurunen M, Valkonen K, Nieminen M, Sinisalo J (2014) Coagulation changes in Takotsubo cardiomyopathy support acute phase reaction and catecholamine excess, but not thrombus production. Int J Cardiol 177:1063–1065

    Article  PubMed  Google Scholar 

  24. Ajmani RS, Fleg JL, Demehin AA, Wright JG, O’Connor F, Heim JM, Tarien E, Rifkind JM (2003) Oxidative stress and hemorheological changes induced by acute treadmill exercise. Clin Hemorheol Microcirc 28:29–40

    CAS  PubMed  Google Scholar 

  25. Chiocchia G, Motais R (1989) Effect of catecholamines on deformability of red cells from trout: relative roles of cyclic AMP and cell volume. J Physiol 412:321–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cecchi E, Parodi G, Giglioli C, Passantino S, Bandinelli B, Liotta AA, Bellandi B, Cioni G, Costanzo M, Abbate R, Gensini GF, Antoniucci D, Mannini L (2013) Stress-induced hyperviscosity in the pathophysiology of Takotsubo cardiomyopathy. Am J Cardiol 111:1523–1529

    Article  PubMed  Google Scholar 

  27. Cecchi E, Parodi G, Fatucchi S, Angelotti P, Giglioli C, Gori AM, Bandinelli B, Bellandi B, Sticchi E, Romagnuolo I, Mannini L, Antoniucci D, Abbate R (2016) Prevalence of thrombophilic disorders in Takotsubo patients: the (ThROmbophylia in Takotsubo cardiomyopathy) TROTA study. Clin Res Cardiol 105:717–726

    Article  CAS  PubMed  Google Scholar 

  28. Delgado GA, Truesdell AG, Kirchner RM, Zuzek RW, Pomerantsev EV, Gordon PC, Regnante RA (2011) An angiographic and intravascular ultrasound study of the left anterior descending coronary artery in Takotsubo cardiomyopathy. Am J Cardiol 108:888–891

    Article  PubMed  Google Scholar 

  29. Eitel I, Stiermaier T, Graf T, Moller C, Rommel KP, Eitel C, Schuler G, Thiele H, Desch S (2016) Optical coherence tomography to evaluate plaque burden and morphology in patients with Takotsubo syndrome. J Am Heart Assoc 5:e004474

    Article  PubMed  PubMed Central  Google Scholar 

  30. Prasad A, Lerman A, Rihal CS (2008) Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 155:408–417

    Article  PubMed  Google Scholar 

  31. International Committee for Standardization in Haematology (1986) Guidelines for measurement of blood viscosity and erythrocyte deformability. Clin Hemorheol 6:439–453

    Google Scholar 

  32. Bennett-Guerrero E, Veldman TH, Doctor A, Telen MJ, Ortel TL, Reid TS, Mulherin MA, Zhu H, Buck RD, Califf RM, McMahon TJ (2007) Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci USA 104:17063–17068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force Members; Document Reviewers (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37:2129–2200

    Article  PubMed  Google Scholar 

  34. Nef HM, Möllmann H, Akashi YJ, Hamm CW (2010) Mechanisms of stress (Takotsubo) cardiomyopathy. Nat Rev Cardiol 7:187–193

    Article  PubMed  Google Scholar 

  35. Akashi YJ, Nef HM, Lyon AR (2015) Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol 12:387–397

    Article  PubMed  Google Scholar 

  36. Said SM, Saygili E, Rana OR, Genz C, Hahn J, Bali R, Varshney S, Albouaini K, Prondzinsky R, Braun-Dullaeus RC (2016) Takotsubo cardiomyopathy: what we have learned in the last 25 years? A comparative literature review. Curr Cardiol Rev 12:297–303

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kume T, Akasaka T, Kawamoto T, Yoshitani H, Watanabe N, Neishi Y, Wada N, Yoshida K (2005) Assessment of coronary microcirculation in patients with takotsubo-like left ventricular dysfunction. Circ J 69:934–939

    Article  PubMed  Google Scholar 

  38. Ono R, Falcão LM (2016) Takotsubo cardiomyopathy systematic review: pathophysiologic process, clinical presentation and diagnostic approach to Takotsubo cardiomyopathy. Int J Cardiol 209:196–205

    Article  PubMed  Google Scholar 

  39. Morel O, Sauer F, Imperiale A, Cimarelli S, Blondet C, Jesel L, Trinh A, De Poli F, Ohlmann P, Constantinesco A, Bareiss P (2009) Importance of inflammation and neurohumoral activation in Takotsubo cardiomyopathy. J Card Fail 15:206–213

    Article  CAS  PubMed  Google Scholar 

  40. Spengler MI, Goñi GM, Mengarelli G, Bravo Luna M, Bocanera R, Tozzini R, Rasia ML (2003) Effect of hormone replacement therapy upon haemorheological variables. Clin Hemorheol Microcirc 28:13–19

    CAS  PubMed  Google Scholar 

  41. Sakashita T, Nobuzane T, Miyoshi H, Fujiwara H, Kudo Y (2009) Effects of menopause and hormone therapy on erythrocyte deformability. Menopause 16:555–558

    Article  PubMed  Google Scholar 

  42. Maturana MA, Irigoyen MC, Spritzer PM (2007) Menopause, estrogens, and endothelial dysfunction: current concepts. Clinics (Sao Paulo) 62:77–86

    Article  Google Scholar 

  43. Bakker N, Schoorl M, Stoutjesdijk E, Houdijk APJ (2020) Erythrocyte deformability and aggregability in patients undergoing colon cancer surgery and effects of two infusions with omega-3 fatty acids. Clin Hemorheol Microcirc 74:287–297

    Article  CAS  PubMed  Google Scholar 

  44. Bakker N, Schoorl M, Demirkiran A, Cense HA, Houdijk APJ (2020) Erythrocyte deformability and aggregation in morbidly obese women undergoing laparoscopic gastric bypass surgery and effects of oral omega-3 fatty acid supplementation. Clin Hemorheol Microcirc 75:303–311

    Article  CAS  PubMed  Google Scholar 

  45. Ho M, Maple C, Bancroft A, McLaren M, Belch JJ (1999) The beneficial effects of omega-3 and omega-6 essential fatty acid supplementation on red blood cell rheology. Prostaglandins Leukot Essent Fatty Acids 61:13–17

    Article  CAS  PubMed  Google Scholar 

  46. Rillaerts E, Van Camp K, Vandewoude MF, Rademakers F, De Leeuw I (1989) Blood viscosity parameters in coronary heart disease: effect of fish oil supplementation. Acta Clin Belg 44:17–23

    Article  CAS  PubMed  Google Scholar 

  47. Cartwright IJ, Pockley AG, Galloway JH, Greaves M, Preston FE (1985) The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. Atherosclerosis 55:267–281

    Article  CAS  PubMed  Google Scholar 

  48. Mills DE, Galey WR, Dixon H (1993) Effects of dietary fatty-acid supplementation on fatty-acid composition and deformability of young and old erythrocytes. Biochim Biophys Acta 1149:313–318

    Article  CAS  PubMed  Google Scholar 

  49. Bor-Kucukatay M, Wenby RB, Meiselman HJ, Baskurt OK (2003) Effects of nitric oxide on red blood cell deformability. Am J Physiol Heart Circ Physiol 284:H1577–H1584

    Article  CAS  PubMed  Google Scholar 

  50. Bor-Kucukatay M, Meiselman HJ, Başkurt OK (2005) Modulation of density-fractionated RBC deformability by nitric oxide. Clin Hemorheol Microcirc 33:363–367

    CAS  PubMed  Google Scholar 

  51. Ludolph B, Bloch W, Kelm M, Schulz R, Kleinbongard P (2007) Short-term effect of the HMG-CoA reductase inhibitor rosuvastatin on erythrocyte nitric oxide synthase activity. Vasc Health Risk Manag 3:1069–1073

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiac Thoracic and Vascular Medicine, Center for Atherothrombotic Diseases, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

    Rossella Marcucci, Lucia Mannini, Brunella Bandinelli & Anna Maria Gori

  2. Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy

    Rossella Marcucci, Anna Maria Gori & Salvatore Mario Romano

  3. General Cardiology Unit, Department of Cardiac Thoracic and Vascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85, 50141, Florence, Italy

    Valentina Andrei, Serena Fatucchi, Cristina Giglioli, Salvatore Mario Romano, Chiara Piazzai, Niccolo’ Marchionni & Emanuele Cecchi

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  1. Rossella Marcucci
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  2. Lucia Mannini
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Correspondence to Emanuele Cecchi.

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This study was performed in accordance with the principles of the 1964 Helsinki Declaration and its later amendments and was approved by the Ethics Committee of the Azienda Ospedaliero-Universitaria Careggi in Florence.

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Marcucci, R., Mannini, L., Andrei, V. et al. Transient stress-related hyperviscosity and endothelial dysfunction in Takotsubo syndrome: a time course study. Heart Vessels 37, 1776–1784 (2022). https://doi.org/10.1007/s00380-022-02071-6

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