Chemotherapy and Valvopathy

Is there a relation between them?

The international literature has pointed out for many years that patients who have undergone treatments with thoracic radiotherapy and whose hearts have been exposed to high doses of radiation have evolved with valve disease over the years. The explanation for this is in the actinic lesion that, over the years, leads to progressive fibrosis and calcification.

Much of this work has been done in patients surviving Hodgkin’s lymphoma, since many were treated as children or adolescents and as adults, it would be possible to assess the long-term impact. In this group of patients, many of them underwent the combined treatment of radiotherapy and chemotherapy and by comparing the evolution of these individuals; it was possible to infer some points.

The most used chemotherapy regimen contained anthracycline and its isolated use was associated with an increase in the rates of heart valve diseases, among other cardiovascular diseases, such as coronary and left ventricular systolic dysfunction. Higher doses of anthracycline lead to a higher incidence of valve involvement (up to 200mg/m2, there was almost no risky incidence, rising to 3.3 times in doses of 350-880mg/m2). It used to be common to imagine that the valve dysfunction was mainly due to the secondary involvement of the mitral valve, due to a ventricular dilation caused by the chemotherapy myocardiotoxicity. However, a group of Norwegian researchers published in JACC imagingin 2016 a follow-up of approximately 13 years after treatment of Hodgkin’s lymphoma, both in patients with isolated radiation therapy, isolated chemotherapy and joint treatment. The study concluded that anthracycline use alone increased the incidence of valvular heart disease 3 times. In this publication, the most prevalent valve disease was aortic valve injury.

Of course, the main criticism of this work was the relatively small number of the cohort study. Larger works usually show the functional impairment of the mitral valve, but sub-analyzes of other works reveal interesting data. Even in the case of mitral regurgitation disease, we saw that the diameters and systolic function of the left ventricle did not differ significantly between the groups, which suggests that we have primary involvement of the leaflet or valve apparatus.

The conclusion we can draw from these works does not end our knowledge on the subject, but makes us believe that just as we have drugs that primarily affect heart valves, such as ergot derivatives or drugs metabolized to norfenfluramine, the use of anthracycline may lead to the same damage, which can cause valve endothelium fibrosis and/or lesion.

The incidence of this valve involvement is dose dependent in the case of anthracycline, as well as it is dose dependent in the case of radiation.

The combined treatment of chemotherapy and radiotherapy further increases the incidence of long-term valve repercussions in survivors.

Suggested literature:

1 – Crawford MH. Chemotherapy-Induced Valvular Heart Disease. JACC Cardiovasc Imaging. 2016 Mar;9(3):240-2.

2 – Murbraech K, Wethal T, Smeland KB, et al. Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study. JACC Cardiovasc Imaging. 2016 Mar;9(3):230-9.

3 – Andrejak M, Tribouilloy C. Drug-induced valvular heart disease: an update. Arch Cardiovasc Dis. 2013 May;106(5):333-9.

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