Kardiotoxische Komplikationen und Herzinsuffizienz durch Radio- und Chemotherapie

Abstract

We review the mechanisms of cardiotoxicity of cytotoxic chemotherapies, the substances associated with a particular high risk of cardiac damage, the clinical signs and symptoms of cardiotoxicity with special emphasis on cardiac failure, and the prevention and therapy of possible cardiotoxic effects. Generally, chemotherapy-induced cardiotoxicity is defined as a reduction of the left-ventricular ejection fraction (LVEF) of more than 5 % to less than 55 % with clinical signs of heart failure or as a reduction of the left-ventricular ejection fraction (LVEF) of more than 10 % to less than 55 % without clinical signs of heart failure. The cardiotoxicity of anthracyclines such as doxorubicin results in limitations of the use of this chemotherapeutic class in the treatment of malignant diseases in 5 – 20 % of patients due to asymptomatic impairment of left ventricular function and in 1 – 5 % of patients due to symptomatic heart failure. The common use of trastuzumab, a monoclonal antibody against „human epidermal growth factor receptor 2“ (HER2), has resulted in an incidence of cardiotoxicity – commonly as asymptomatic impairment of left ventricular function or even as symptomatic cardiac failure – in up to 10 % with monotherapy and in up to 30 % in combination with anthracyclines. The prevention of cardiotoxicity, the early detection by echocardiography and measurement of troponin, prompt therapy, and a meticulous cardiological work up of individual risk factors and cardiac comorbidities are essential for the reduction of potentially cardiotoxic effects of cytotoxic chemotherapy.

Kernaussagen

• Essenziell ist die Kenntnis möglicher kardiotoxischer Effekte vor Einleitung einer Chemotherapie mit anthrazyklinhaltigen Substanzen und monoklonalen Antikörpern wie Trastuzumab.

• Ein sorgfältiges kardiovaskuläres diagnostisches „work up“ von individuellen Risikofaktoren und kardialen Komorbiditäten ist vor Durchführung einer potenziell kardiotoxischen Radiochemotherapie notwendig.

• Eine adäquate Einstellung kardiovaskulärer Risikofaktoren und leitlinienorientierte Behandlung kardialer Komorbiditäten wie arterieller Hypertonie und linksventrikulärer systolischer und/oder diastolischer Dysfunktion können mögliche spätere kardiotoxische Effekte minimieren.

• Eine regelmäßige klinische Untersuchung zur Beurteilung kardialer Nebenwirkungen und Komplikationen sollte im Follow-up einer potenziell kardiotoxischen Chemotherapie gewährleistet sein.

• Die Troponinbestimmung und die longitudinale Strain-Bestimmung in der Echokardiografie sind geeignete Parameter zur Früherkennung kardiotoxischer Komplikationen und sollten grundsätzlich zur Überwachung von Patienten unter einer potenziell kardiotoxischen Polychemotherapie eingesetzt werden.

• Patienten mit einer kardiotoxischinduzierten Herzinsuffizienz werden entsprechend den Leitlinien zur Therapie der Herzinsuffizienz behandelt.

• Grundsätzlich sollte eine interdisziplinäre Zusammenarbeit zwischen Onkologen und Kardiologen zur Prävention kardiotoxischer Komplikationen etabliert werden.

• Literatur

• 1 Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin. Cancer 2003; 97: 2869-2876
• 2 Martin M, Esteva FJ, Alba E et al. Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations. Oncologist 2009; 14: 1-11
• 3 Yeh ETH, Tong AT, Lenihan DJ et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation 2004; 109: 3122-3131
• 4 Adams MJ, Lipsitz SR, Colan SD et al. Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol 2004; 22: 3139-3148
• 5 Heidenreich PA, Hancock SL, Vagelos RH et al. Diastolic dysfunction after mediastinal irradiation. Am J Heart J 2005; 150: 977-982
• 6 Gyenes G, Rutqvist LE, Liedberg A et al. Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer. Radiother Oncol 1998; 48: 185-190
• 7 Eschenhagen Th, Force Th, Ewer MS et al. Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Europ J Heart Failure 2011; 13: 1-10
• 8 Lipshultz S, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart 2008; 94: 525-533
• 9 Yeh ETH, Bickford CL. Cardiovascular complications of cancer therapy. J Am Coll Cardiol 2009; 53: 2231-2234
• 10 Elliot P. Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol 2006; 33: 2-11
• 11 Cardinale D, Colombo A, Torrisi R et al. Trastuzumab – induced cardiotoxicity. Clinical and prognostic implications of troponin I evaluation. J Clin Oncol 2010; 28: 3910-3916
• 12 Ewer SE, Ewer SM. Troponin I provides insight into cardiotoxicity and the anthracycline-trastuzumab interaction. J Clin Oncol 2010; 28: 3901-3904
• 13 Fallah-Rad N, Walker JR, Wassef A 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: 2263-2270
• 14 Sawaya H, Sebag IA, Plana JC et al. Early detection and prediction of cardiotoxicity in chemotherapy – treated patients. Am J Cardiol 2011; 107: 1375-1380
• 15 Ho E, Brown A, Barrett P et al. Subclinical anthracycline- and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study. Heart 2010; 96: 701-707
• 16 Dolci A, Dominici R, Cardinale D et al. Biochemical markers of the literature and recommendations for use. Am J Clin Pathol 2008; 130: 688-695
• 17 Cardinale D, Sandri MT, Colombo A et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 2004; 109: 2749-2754
• 18 Cardinale D, Colombo A, Sandri MT et al. Prevention of high – dose chemotherapy induced cardiotoxicity in high - risk patients by angiotensin – converting enzyme inhibition. Circulation 2006; 114: 2474-2481
• 19 Jones LW, Haykowsky MJ, Swartz JJ et al. Early Breast Cancer therapy and cardiovascular injury. J Am Coll Cardiol 2007; 50: 1435-1441
• 20 Batist G, Ramakrishnaa G, Rao CS et al. Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol 2001; 19: 1444-1454