RAMB Março/Abril 2016

ardiovascular

effects

radiotherapy

the

patient

with

cancer

ssoc

ras

2016; 62(2):192-196

193

particles. The biological effects of radiation can be di-

rect or indirect. It is considered a direct effect when in-

teracting with the cellular components, proteins and lip-

ids, causing them to undergo structural changes. In

indirect interaction, the effect occurs in the medium

where the cells and their constituents are suspended, that

is, water, with the production of free radicals. Free radi-

cals are atoms or molecules that are unstable and high-

ly reactive. Seeking an electronic balance causes the free

radicals to break chemical bonds in search of an electron.

The biological response to irradiation can lead to a large

number of changes like breakage to double-stranded

DNA, chromosome rearrangements and breakage, trans-

location of lipid molecules in the membrane, death by

apoptosis or cell division, mutation and carcinogenesis.

Radiation therapy is an important component of the

therapeutic arsenal for the treatment of breast CA, Hod-

gkin’s disease, lung CA and other tumors involving the

cervical and thoracic regions and is linked to increased

cardiovascular morbidity and mortality. Concerns about

cardiovascular lesions (CV) induced by RT in patients ir-

radiated for treatment of cervical and thoracic cancers

have occurred for decades.

4,5

Cardiovascular morbidity

and mortality is proportional to the dose of radiation

and the site exposed in the CV unit.

6-12

Therapeutic

advances for clinical control or curing of CA and better

support for treatment-related complications have provided

a greater survival rate to patients, with enough time to

develop late-onset cardiovascular sequelae from RT.

The

cardiac effects of RT in the long term are heterogeneous

and include coronary artery disease, valve disease; diseas-

es of pericardium; myocardial diseases, with systolic and

diastolic dysfunction in particular; and conduction sys-

tem disturbances.

Major vessels and carotid arteries may

also be involved.

14,15

amage

the

pericardium

The most common cardiac abnormality resulting from

thoracic irradiation, especially of the mediastinum, is

pericardial damage that manifests as fibrous thickening

and serofibrinous effusion that can progress to cardiac

tamponade and/or constrictive pericarditis.

13,16

Indepen-

dent clinical factors that may predict the predisposition

to pericardial damage have not yet been identified.

17,18

the past, pericardial disease induced by radiation has been

underestimated. The treatment applied was pericardio-

centesis in those that evolved with cardiac tamponade,

which resulted in increased mortality. It was assumed that

pericardial effusion accounted for the severity of the co-

existent illness and not the cardiotoxic effect secondary

to radiotherapy. In patients who develop pericardial thick-

ening, associated with pericardial effusion or otherwise,

in which is there is an increase in the final diastolic pres-

sure of the right chambers evidenced via cardiac cathe-

terization, the best treatment is pericardiectomy, given

that the central venous pressure is reduced to normal im-

mediately after the procedure, in addition to good clini-

cal evolution with disappearance of the symptoms of car-

diac dysfunction.

However, in patients with pericardial

thickening without high intracavitary pressures, rigor-

ous clinical monitoring seems appropriate. Simple drain-

age of the effusion is not recommended because the dis-

ease can evolve with more marked fibrosis and consequent

constriction, meaning that it appears reasonable to re-

move the maximum possible parietal pericardium.

oronary

artery

disease

Incidental exposure of the heart to RT increases the inci-

dence of accelerated or premature coronary artery disease

(CAD),

20-22

commonly identified in young or relatively

young patients with none of the major risk factors for

atherogenesis, such as smoking, diabetes mellitus, dys-

lipidemia, hypertension and a family history of early ath-

erosclerosis.

16,21,23

CAD risk begins to increase during the

first five years after irradiation and continues for at least

20 years.

21,22

There is no statistically significant difference

between patients with or without risk factors for CAD at

the time of radiotherapy.

The increase in CAD is direct-

ly proportional to the average dose of radiation and heart

volume included in the RT field.

20,22-24

The obstructive le-

sions of the epicardial vessels are most often proximal

and in more than 80% of the cases the lesion occurs in

the coronary artery. This can affect the coronary os-

tia.

14,16,20,24,25

as they occupy the region with greatest risk

of being included in the irradiation fields.

Under mi-

croscopy it is possible to observe fibrointimal thickening,

fibroproliferative lesions, fibrocalcific and also fibrolipid

plaques in the areas of coronary stenosis.

The plaques

in irradiated patients are more fibrous with little lipid

content.

Some factors such as more frequent proximal impair-

ment affecting the trunk of the left coronary artery and

proximal anterior descending artery, and the high prev-

alence of associated significant valvular disease lead many

patients to being recommended for cardiac surgery. How-

ever, the results of such treatment do not necessarily cor-

respond to what would be expected in a population that

has not been irradiated. In the postoperative period of

patients with lesions from RT there is longer hospitaliza-

tion time, incidence of atrial fibrillation, pacemaker im-