Diagnosis of Cardiac Damage: Role of Stress Echo

  • Ciro Santoro
  • Roberta Esposito
  • Covadonga Fernández-Golfín
  • Maurizio GalderisiEmail author
  • Jose Luis Zamorano Gomez
Part of the Current Clinical Pathology book series (CCPATH)


Stress echocardiography represents a valuable technique to reveal occult left ventricular dysfunction and coronary artery disease induced by chemo- and radiotherapy treatments. Indeed stress echocardiography can drive rapid cardiac intervention in terms of both chemotherapy dosage reduction and cardio protective strategies. Main indications for stress echocardiography are (i) suspect of coronary artery disease, (ii) evaluation of newly diagnosed LV dysfunction and (iii) assessment of new-onset valvular heart disease. The principal stressors used to reveal chemotherapy-induced cardiac damage are exercise, dobutamine and dipyridamole. Since sensitivity and specificity of different stressors are almost comparable, in cancer patients, the choice of the stressor can be selected according to safety, side effects and efficacy. To detect early signs of left ventricular dysfunction induced by chemotherapy, a complete evaluation of systolic and diastolic function at rest and after stress should be performed. Contractile reserve assessed by either ejection fraction or speckle tracking echocardiography should be determined considering its diagnostic and prognostic power. New technologies applied to stress echocardiography, such as three-dimensional evaluation, would overcome temporal and geometric assumption, but it shows several limitations that reduce its use in clinical practice.


LV dysfunction Stress echocardiography Coronary artery disease LV longitudinal function Speckle tracking echocardiography 


  1. 1.
    Bird BR, Swain SM. Cardiac toxicity in breast cancer survivors: review of potential cardiac problems. Clin Cancer Res. 2008;14:14–24.CrossRefGoogle Scholar
  2. 2.
    Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710–7.CrossRefGoogle Scholar
  3. 3.
    Marks LB, Yu X, Prosnitz RG, Zhou SM, Hardenbergh PH, Blazing M, et al. The incidence and functional consequences of RT-associated cardiac perfusion defects. Int J Radiat Oncol Biol Phys. 2005;63:214–23.CrossRefGoogle Scholar
  4. 4.
    Jones RL, Swanton C, Ewer MS. Anthracycline cardiotoxicity. Expert Opin Drug Saf. 2006;5:791–809.CrossRefGoogle Scholar
  5. 5.
    Martin M Jr, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, et al. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013;14:72–80.CrossRefGoogle Scholar
  6. 6.
    Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79.CrossRefGoogle Scholar
  7. 7.
    Neugut AI, Jacobson JS, Grann VR, Hershman DL. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23:8597–605.CrossRefGoogle Scholar
  8. 8.
    Khouri MG, Douglas PS, Mackey JR, Martin M, Scott JM, Scherrer-Crosbie M, et al. Cancer therapy-induced cardiac toxicity in early breast cancer: addressing the unresolved issues. Circulation. 2012;126:2749–63.CrossRefGoogle Scholar
  9. 9.
    Jones LW, Haykowsky MJ, Swartz JJ, Douglas PS, Mackey JR. Early breast cancer therapy and cardiovascular injury. J Am Coll Cardiol. 2007;50:1435–41.CrossRefGoogle Scholar
  10. 10.
    Drafts BC, Twomley KM, D’Agostino R Jr, Lawrence J, Avis N, Ellis LR, et al. Low to moderate dose anthracycline-based chemotherapy is associated with early non-invasive imaging evidence of subclinical cardiovascular disease. JACC Cardiovasc Imaging. 2013;6:877–85.CrossRefGoogle Scholar
  11. 11.
    Dolci A, Dominici R, Cardinale D, Sandri MT, Panteghini M. Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol. 2008;130:688–95.CrossRefGoogle Scholar
  12. 12.
    Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57:2263–70.CrossRefGoogle Scholar
  13. 13.
    Ganz WI, Sridhar KS, Ganz SS, Gonzalez R, Chakko S, Serafini A. Review of tests for monitoring doxorubicin-induced cardiomyopathy. Oncology. 1996;53:461–70.CrossRefGoogle Scholar
  14. 14.
    Goethals I, De Winter O, De Bondt P, De Sutter J, Dierckx R, Van De Wiele C. The clinical value of nuclear medicine in the assessment of irradiation-induced and anthracycline-associated cardiac damage. Ann Oncol. 2002;13:1331–9.CrossRefGoogle Scholar
  15. 15.
    Plana JC. Chemotherapy and the heart. Rev Esp Cardiol (Engl Ed). 2011;64:409–15.CrossRefGoogle Scholar
  16. 16.
    Santoro C, Arpino G, Esposito R, Lembo M, Paciolla I, Cardalesi C, et al. 2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility. Eur Heart J Cardiovasc Imaging. 2017;18:930–6.CrossRefGoogle Scholar
  17. 17.
    Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2768–801.CrossRefGoogle Scholar
  18. 18.
    Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2014;15:1063–93.CrossRefGoogle Scholar
  19. 19.
    Civelli M, Cardinale D, Martinoni A, Lamantia G, Colombo N, Colombo A, et al. Early reduction in left ventricular contractile reserve detected by dobutamine stress echo predicts high-dose chemotherapy-induced cardiac toxicity. Int J Cardiol. 2006;111:120–6.CrossRefGoogle Scholar
  20. 20.
    Khouri MG, Hornsby WE, Velazquez EJ, Jones LW, Douglas PS. Exercise stress testing with strain echocardiography is superior to resting echocardiography in identifying doxorubicin-induced preclinical LV dysfunction in breast cancer patients. Circulation. 2011;124:A16399.Google Scholar
  21. 21.
    Correa CR, Das IJ, Litt HI, Ferrari V, Hwang WT, Solin LJ, et al. Association between tangential beam treatment parameters and cardiac abnormalities after definitive radiation treatment for left-sided breast cancer. Int J Radiat Oncol Biol Phys. 2008;72:508–16.CrossRefGoogle Scholar
  22. 22.
    Kohli P, Gulati M. Exercise stress testing in women: going back to the basics. Circulation. 2010;122:2570–80.CrossRefGoogle Scholar
  23. 23.
    Beckman JA, Thakore A, Kalinowski BH, Harris JR, Creager MA. Radiation therapy impairs endothelium-dependent vasodilation in humans. J Am Coll Cardiol. 2001;37:761–5.CrossRefGoogle Scholar
  24. 24.
    Corn BW, Trock BJ, Goodman RL. Irradiation-related ischemic heart disease. J Clin Oncol. 1990;8:741–50.CrossRefGoogle Scholar
  25. 25.
    Gaya AM, Ashford RF. Cardiac complications of radiation therapy. Clin Oncol (R Coll Radiol). 2005;17:153–9.CrossRefGoogle Scholar
  26. 26.
    Virmani R, Farb A, Carter AJ, Jones RM. Pathology of radiation-induced coronary artery disease in human and pig. Cardiovasc Radiat Med. 1999;1:98–101.CrossRefGoogle Scholar
  27. 27.
    Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087–106.CrossRefGoogle Scholar
  28. 28.
    Heidenreich PA, Schnittger I, Strauss HW, Vagelos RH, Lee BK, Mariscal CS, et al. Screening for coronary artery disease after mediastinal irradiation for Hodgkin’s disease. J Clin Oncol. 2007;25:43–9.CrossRefGoogle Scholar
  29. 29.
    Lancellotti P, Nkomo VT, Badano LP, Bergler-Klein J, Bogaert J, Davin L, et al. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2013;14:721–40.CrossRefGoogle Scholar
  30. 30.
    Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, et al. Stress echocardiography expertconsensus statement. Eur J Echocardiogr. 2008;9:415–37.CrossRefGoogle Scholar
  31. 31.
    Heijenbrok-Kal MH, Fleischmann KE, Hunink MG. Stress echocardiography, stress single-photon-emission computed tomography and electron beam computed tomography for the assessment of coronary artery disease: a meta-analysis of diagnostic performance. Am Heart J. 2007;154:415–23.CrossRefGoogle Scholar
  32. 32.
    Schwartz RG, McKenzie WB, Alexander J, Sager P, D'Souza A, Manatunga A, et al. Congestive heart failure and left ventricular dysfunctioncomplicating doxorubicin therapy: a seven year experience using serialradionuclide angiocardiography. Am J Med. 1987;82:1109–18.CrossRefGoogle Scholar
  33. 33.
    Varga A, Garcia MA, Picano E, International Stress Echo Complication Registry. Safety of stress echocardiography (from the International Stress Echo Complication Registry). Am J Cardiol. 2006;98:541–3.CrossRefGoogle Scholar
  34. 34.
    Picano E, Marini C, Pirelli S, Maffei S, Bolognese L, Chiriatti G, et al. Safety of intravenous high-dosedipyridamole echocardiography. The Echo-Persantine International Cooperative Study Group. Am J Cardiol. 1992;70:252–8.CrossRefGoogle Scholar
  35. 35.
    Picano E, Mathias W Jr, Pingitore A, Bigi R, Previtali M. Safety and tolerability ofdobutamine-atropine stress echocardiography: a prospective, multicentrestudy. Echo Dobutamine International Cooperative Study Group. Lancet. 1994;344:1190–2.CrossRefGoogle Scholar
  36. 36.
    Beckmann S, Haug G. National registry 1995–1998 on 150,000 stress echo examinations side effects and complications in 60,448 examinations of the registry 1997–1998. Circulation. 1999;100(Suppl):3401A.Google Scholar
  37. 37.
    Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, et al. Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction. Circulation. 1993;88:405–15.CrossRefGoogle Scholar
  38. 38.
    Rigo F, Richieri M, Pasanisi E, Cutaia V, Zanella C, Della Valentina P, et al. Usefulness of coronary flow reserve over regional wall motion when added to dual-imaging dipyridamole echocardiography. Am J Cardiol. 2003;91:269–73.CrossRefGoogle Scholar
  39. 39.
    Nohtomi Y, Takeuchi M, Nagasawa K, Arimura K, Miyata K, Kuwata K, et al. Simultaneous assessment of wall motion and coronary flow velocity in the left anterior descending coronary artery during dipyridamole stress echocardiography. J Am Soc Echocardiogr. 2003;17:457–63.CrossRefGoogle Scholar
  40. 40.
    Lowenstein J, Tiano C, Marquez G, Presti C, Quiroz C. Simultaneous analysis of wall motion and coronary flow reserve of the left anterior descending coronary artery by transthoracic doppler echocardiography during dipyridamole stress. J Am Soc Echocardiogr. 2003;17:735–44.Google Scholar
  41. 41.
    Cerqueira MD. Pharmacologic stress versus maximal-exercise stress for perfusion imaging: which, when, and why? J Nucl Cardiol. 1996;3:S10–4.CrossRefGoogle Scholar
  42. 42.
    Tamargo J, Caballero R, Delpón E. Cancer chemotherapy and cardiac arrhythmias: a review. Drug Saf. 2015;38(2):129–52.CrossRefGoogle Scholar
  43. 43.
    Marwick TH, Shaw L, Case C, Vasey C, Thomas JD. Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice. Eur Heart J. 2003;24:1153–63.CrossRefGoogle Scholar
  44. 44.
    Crouse LJ, Cheirif J, Hanly DE, Kisslo JA, Labovitz AJ, Raichlen JS, et al. Opacification and border delineation improvement inpatients with suboptimal endocardial border definition in routineechocardiography: results of the Phase III Albunex Multicenter Trial. J Am Coll Cardiol. 1993;22:1494–500.CrossRefGoogle Scholar
  45. 45.
    Ewer MS, Lenihan DJ. Left ventricular ejection fraction and cardiotoxicity: is our ear really to the ground? J Clin Oncol. 2008;26:1201–3.CrossRefGoogle Scholar
  46. 46.
    McKillop JH, Bristow MR, Goris ML, Billingham ME, Bockemuehl K. Sensitivity and specificity of radionuclide ejection fractions in doxorubicin cardiotoxicity. Am Heart J. 1983;106:1048–56.CrossRefGoogle Scholar
  47. 47.
    Ilardi F, Santoro C, Cirillo P, Esposito G, Trimarco B, Galderisi M. Quantitative detection of inducible ischemia during dobutamine stress by speckle racking echocardiography: a dream comes true. Int J Cardiol. 2016;220:357–9.CrossRefGoogle Scholar
  48. 48.
    Argyle RA, Ray SG. Stress and strain: double trouble or useful tool? Eur J Echocardiogr. 2009;10:716–22.CrossRefGoogle Scholar
  49. 49.
    Gyenes G, Fornander T, Carlens P, Rutqvist LE. Morbidity of ischemic heart disease in early breast cancer 15-20 years after adjuvant radiotherapy. Int J Radiat Oncol Biol Phys. 1994;28:1235–41.CrossRefGoogle Scholar
  50. 50.
    Ramahi T. Dobutamine-induced augmentation of left ventricular ejection fraction predicts survival of heart failure patients with severe non-ischaemic cardiomyopathy. Eur Heart J. 2001;22:849–56.CrossRefGoogle Scholar
  51. 51.
    Yildirim A, SedefTunaoglu F, Pinarli FG, Ilhan M, Oguz A, Karadeniz C, et al. Early diagnosis of anthracycline toxicity in asymptomatic long-term survivors: dobutamine stress echocardiography and tissue Doppler velocities in normal and abnormal myocardial wall motion. Eur J Echocardiogr. 2010;11:814–22.CrossRefGoogle Scholar
  52. 52.
    Abusaid GH, Ahmad M. Real time three-dimensional stress echocardiographyadvantages and limitations. Echocardiography. 2012;29:200–6.CrossRefGoogle Scholar
  53. 53.
    Ahmad M, Xie T, McCulloch M, Abreo G, Runge M. Real-time three dimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: comparison with two-dimensional dobutamine stress echocardiography. J Am Coll Cardiol. 2001;37:1303–9.CrossRefGoogle Scholar
  54. 54.
    Pratali L, Molinaro S, Corciu AI, Pasanisi EM, Scalese M, Sicari R. Feasibility of realtimethree-dimensional stress echocardiography: pharmacological and semi-supine exercise. Cardiovasc Ultrasound. 2010;8:10.CrossRefGoogle Scholar
  55. 55.
    Varnero S, Santagata P, Pratali L, Basso M, Gandolfo A, Bellotti P. Head to head comparison of 2D vs real time 3D dipyridamole stress echocardiography. Cardiovasc Ultrasound. 2008;6:31.CrossRefGoogle Scholar
  56. 56.
    Badano LP, Muraru D, Rigo F, Del Mestre L, Ermacora D, Gianfagna P, et al. High volume-ratethree-dimensional stress echocardiography to assess inducible myocardial ischemia: a feasibility study. J Am Soc Echocardiogr. 2010;23:628–35.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ciro Santoro
    • 1
  • Roberta Esposito
    • 1
  • Covadonga Fernández-Golfín
    • 2
  • Maurizio Galderisi
    • 1
    Email author
  • Jose Luis Zamorano Gomez
    • 2
  1. 1.Advanced Biomedical ScienceFederico II University HospitalNaplesItaly
  2. 2.Cardiology DepartmentRamon y Cajal University HospitalMadridSpain

Personalised recommendations