Right from the heart: survivors of childhood cancer and the right ventricle

Survival after childhood cancer has improved significantly during the last decades and now over 83% of children with malignant disease in the USA are expected to become 5-year survivors. 1 In Europe, it is estimated that there are currently 300–500 000 childhood cancer survivors. 2 Acute lymphoblastic leukaemia is common in children with a peak at age 2–5; the treatment includes chemotherapy, radiation and intensive combinations of total body irradiation with bone marrow or stem cell transplants. Childhood lymphoma frequently necessitates treatment with mediastinal radiotherapy and anthracyclines. However, the life-saving oncology treatment at childhood may cause late sequel at adult age, leading to premature morbidity and mortality. Considerable subclinical progressive disease among adult survivors of childhood cancer has been recently identified, necessitating plans to facilitate the continuity and transition of childhood to adult care. 3 Importantly, premature cardiac and vascular diseases occur increasingly in adult childhood cancer survivors. 4 , 5 Especially the exposure to anthracyclines, but also other chemotherapeutic agents, and/or radiotherapy to the mediastinum or chest may generate long-term cardiac toxicity and subsequently, the risk of heart failure is increased 15-fold and of cardiac death 8-fold among adult survivor. Subtle myocardial structural changes up to overt heart failure, premature coronary artery disease and valvular disease have been recognized as late complications of cancer therapy and should be searched for during follow-up by echocardiography and other multimodality imaging. 6–8 The left ventricle (LV) has been well established as common entity involved in early and late cardiotoxicity. 4 , 9 Reduction in LV systolic ejection fraction and myocardial strain, similar to adult e.g. breast cancer therapy, 10 , 11 and also even reduction in LV myocardial wall thickness and LV mass after childhood cancer therapy have been increasingly identified in recent studies. 9 However, not much is known about the effects of childhood cancer treatment on the right ventricle (RV), and smaller studies pointed to different patterns of left or right ventricular response. Christiansen et al.12 examined a large group of adult patients with a long follow-up, having survived childhood lymphoma or acute lymphoblastic leukaemia with extensive focus on RV function and dimensions by echocardiography. The cohort comprised 246 survivors with a mean of 21.7 years after the diagnosis, identified through the Cancer Registry of Norway, and was compared with a similar large control group of 211 matched healthy persons from the Norwegian HUNT study. 13 Of the survivors, 207 patients (84%) had been exposed to anthracyclines and/ or mediastinal irradiation as children. Strikingly, right ventricular systolic impairment was evident in about one-third (30%) of childhood leukaemia or lymphoma survivors. The study examined different measures of RV function which can be easily performed in the clinical setting, such as tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, and longitudinal 2D speckle tracking strain of the RV free wall, as well as tissue Doppler peak systolic velocity of the tricuspid annulus. The authors observed significantly lower parameters of RV function in all survivor subgroups that had received a cardiotoxic treatment, especially after mediastinal radiation, whereas this was not observed in the small subgroup of cancer survivors who had not been exposed to anthracyclines or radiotherapy. Although the RV impairment was mild in many patients, these findings appear to point to an early stage of the progressive process of cardiotoxicity. The mean age of the survivors was only 31 years; therefore, the observed RV dysfunction might translate into prognostic impact at later age, even though this was not examined in this study. Maybe not surprisingly, RV systolic dysfunction was even more frequent in survivors who also had LV dysfunction, and occurred three times more. Overall, late LV systolic impairment was found in more than 1 of 10 (11%) with history of childhood cancer; furthermore, LV diastolic dysfunction was present in 22% of these young adults. In survivors of childhood Hodgkin's lymphoma, aortic valve stenosis was present in 18%, and some degree of mitral stenosis in 6% of patients. Irradiation of the chest may particularly involve the right heart, leading to later myocardial fibrosis, and the tricuspid valve, as also observed in adult cancer treatment. 6 In the present study, only few patients, however, had tricuspid regurgitation or elevated pulmonary artery pressure. The timely detection of myocardial left—or right—heart dysfunction is important, as prompt initiation of heart failure therapy might influence further progression, although not much is known in adult survivors of childhood cancer and whether underlying, chronic myocardial fibrosis might prevent restoration of ventricular function. 14 , 15 In conclusion, the authors could show that about one-third of survivors of childhood cancer exposed to chemotherapy or mediastinal radiation had impaired RV function at follow-up as adults, and >10% had LV systolic dysfunction. The RV may present a subclinical stage of late cardiotoxicity, occurring even before LV impairment, although the prognostic role is not well defined yet. It is time to get it right—raise awareness for late cardiotoxicity and follow childhood cancer survivors at a regular basis, looking comprehensively at clinical parameters, myocardial biomarkers (e.g. plasma B-type natriuretic peptide), ECG, and most importantly by echocardiography imaging, applying the new techniques available such as 2D speckle tracking strain routinely not only for the left but also for the right side of the heart. Conflict of interest: None declared.