Radiation-induced heart disease

Radiation-induced heart disease, also known as radiation cardiotoxicity, describes an uncommon constellation of potential cardiac complications of thoracic radiotherapy.

Epidemiology

The demographics of patients affected by radiation-induced heart disease are those of the underlying condition for which radiation therapy was performed. Within this population, radiation-induced heart disease is estimated between 10 to 30%, happening in a period of 5 to 10 years after the treatment completion date ⁸.

Clinical presentation

Radiation-induced heart has a variety of potential presentations depending on the part of the heart affected and how long it has been since radiotherapy.

• coronary arteries
  • acute coronary syndrome and angina pectoris
    • prior radiotherapy increases the risk of an acute myocardial infarction by 2-13 times, with the event often occurring years after treatment ^1-6 
    • thought to be the most significant cause of mortality from radiation-induced heart disease ^1-4
    • clinical features are identical to any other cause of acute coronary syndrome (see individual article for a detailed discussion) ^1-4
• pericardium
  • acute pericarditis
    • manifests within weeks of treatment ^1-4
    • signs and symptoms are classic of any other acute pericarditis, such as acute pleuritic chest pain, tachycardia, and a pericardial rub heard on precordial auscultation (see individual article for a detailed discussion) ^1-4
  • delayed pericarditis
    • more common than the acute variant and occurs years after treatment ^1-4
    • also the most common manifestation of radiation-induced heart disease overall ^1-4
    • signs and symptoms are similar to those of acute pericarditis, but can be recurrent ^1-4
  • constrictive pericarditis
    • typically after recurrent episodes of delayed pancreatitis ^1-4
    • signs and symptoms classic of any other constrictive pericarditis (see individual article for a detailed discussion) ^1-4
• valves
  • aortic stenosis
    • most commonly affected and often manifests over a decade after treatment ^1-4
    • clinical presentation is the same as any other cause of aortic stenosis (see individual article for a detailed discussion) ^1-4
  • aortic regurgitation
    • often subclinical, but when symptomatic clinical presentation is the same as any other cause of chronic aortic regurgitation (see individual article for a detailed discussion) ^1-4
  • mitral stenosis
    • clinical presentation is the same as any other cause of mitral stenosis (see individual article for a detailed discussion) ^1-4
• myocardium and conduction system
  • acute myocarditis
    • a rare manifestation that presents similar to any other myocarditis, often with features of severe, acute heart failure (see individual article for a detailed discussion) ⁴
    • often occurs alongside acute pericarditis ⁴
  • myocardial fibrosis (radiation-induced cardiomyopathy)
    • often subclinical unless there has been a history of very high dose radiotherapy ^1-4
    • if symptomatic, presents with non-specific signs and symptoms consistent with heart failure ^1-4
  • arrhythmias
    • atrioventricular block
      • clinical presentation varies depending on the degree and type of the block ^1-4
    • bundle branch block
      • right bundle branch blocks are most common ^1-4
      • clinical presentation varies depending on the location of the block, but is often asymptomatic ^1-4

Pathology

Radiation has numerous direct and indirect effects on the various structures of the heart, many which have been attributed to damage to microvasculature leading to eventual fibrosis ^1-5.

• coronary artery disease
  • the pathophysiology of coronary artery disease is uncertain, but has been likened to accelerated atherosclerosis ^1-5
  • the proximal right coronary artery, proximal left anterior descending artery, and left main coronary artery are most commonly implicated, likely because of their anterior location ^1-5
• pericardial disease
  • acute pericarditis
    • it is likely that inflammation related to the tumor being irradiated is the likely cause of the acute pericarditis, rather than the radiation itself ^1-5
    • this theory is supported by the observation that acute pericarditis often occurs during irradiation of large tumors rather than smaller tumors ^1-5
  • delayed pericarditis and constrictive pericarditis
    • pathological changes are consistent with fibrosis (i.e. fibrinous pericarditis) and eventual thickening of the pericardium that compromises cardiac function (i.e. constrictive pericarditis) ^1-5
    • indeed, autopsy studies have demonstrated pericardial thickening of up to 7 times of normal ⁴
    • the mechanism by which this occurs is uncertain, but is likely due to damage to the pericardial microvasculature leading to ischemia and fibrosis ^1-5
• valvulopathy
  • pathologically characterized by endocardial fibrosis and eventual thickening of the valves, often leading to stenosis and subclinical regurgitation ^1-5
  • left-sided valves (i.e. aortic valve and mitral valve) are thought to be more commonly affected due to the higher pressures compared to the right side of the heart ¹
• myocardial and conduction system disease
  • acute myocarditis
    • similar mechanism to acute pericarditis, likely not directly related to the radiation ⁴
  • myocardial fibrosis (radiation-induced cardiomyopathy)
    • the myocardium was once thought to be resistant to radiation due to the very low rate of myocyte cell division ⁴
    • it is likely that the myocardium is affected due to damage and inflammation to its microvasculature causing ischemia and eventual fibrosis ^1-5
  • arrhythmias
    • arrhythmias occur due to the aforementioned myocardial fibrosis in regions critical to the conduction system, these are most commonly not clinically significant ^1-5
    • right bundle branch blocks are the most common branch block (more common than left bundle branch blocks) due to the right heart having a more anterior location ^1-5

Etiology

Typically, patients have received radiation therapy for one of the following ^1-5:

• mediastinal lymphoma
• esophageal cancer
• thymoma
• lung cancer (especially left-sided)
• breast cancer (especially left-sided)

The risk of developing radiation-induced lung disease depends on a number of factors including ^1-5:

• total dose administered, with the highest risk being with total doses above 44 Gy
• prior or concurrent chemotherapy, especially with anthracyclines (e.g. doxorubicin)
• lack of cardiac protection (e.g. subcarinal blocking)

Radiographic features

Radiographic appearances vary considerably depending on the part of the heart involved ^1,2,4,6. Although plain radiographs, echocardiography, and CT are useful modalities, cardiac MRI is considered to be the best modality for evaluating radiation-induced heart disease ^1,2,4,6. The role of imaging is to provide a diagnosis and assess severity ^1,2,4,6.

Many manifestations of radiation-induced heart disease have radiographic features that are identical to those with different underlying etiologies ^1,2,4,6. In such cases, individual articles should be sought, where a more detailed discussion is presented.

• coronary artery disease
  • a variety of modalities may be employed to assess coronary arteries and associated functional and perfusion defects in these patients, such as stress echocardiography, nuclear myocardial perfusion imaging, CT calcium scoring, and CT coronary angiography (see cardiac CT) ^1,2,4,6
  • one recommendation is to begin scanning patients 5 years post-treatment if they were older than 45 years during treatment, or 10 years post-treatment if they were younger than 45 years during treatment ²
• pericardial disease
  • acute pericarditis
    • radiographic changes are consistent with any other cause of acute pericarditis, pericardial effusion is also commonly present (see the individual articles for detailed discussions) ^1,2,4,6
    • often imaging is not necessary as the diagnosis can be made clinically ^1,2,4,6
  • delayed pericarditis and constrictive pericarditis
    • radiographic changes are consistent with any other cause of fibrinous pericarditis or constrictive pericarditis, pericardial effusion is also commonly present (see the individual articles for detailed discussions) ^1,2,4,6
    • in general, CT is the best modality for identifying pericardial calcifications however MRI is otherwise superior ^1,2,4,6
  • valvulopathy
    • radiographic changes are consistent with any other cause of the individual valvulopathies (see the articles on aortic stenosis, aortic regurgitation, and mitral stenosis for detailed discussions) ^1,2,4,6
    • generally, echocardiography is considered the most pragmatic imaging modality for screening purposes ^1,2,4,6
• myocardium and conduction system disease
  • acute myocarditis
    • radiographic changes are consistent with any other cause of acute myocarditis (see the individual article for a detailed discussion) ^1,2,4,6
  • myocardial fibrosis (radiation-induced cardiomyopathy)
    • echocardiography is a useful screening modality to assess for systolic or diastolic dysfunction ^1,2,4,6
    • however, cardiac MRI is the optimal imaging modality for assessing cardiac function and distinguishing it from other restrictive cardiomyopathies ^1,2,4,6
      • for example, delayed enhancement images may demonstrate features of myocardial fibrosis that does not correspond to a coronary territory or to a pattern consistent with other restrictive cardiomyopathies (e.g. amyloidosis, sarcoidosis) ⁷
  • arrhythmias
    • generally, imaging is not indicated or useful

Treatment and prognosis

Management depends on the part of the heart involved and the severity of the resultant disease.

• coronary artery disease
  • stenting, ideally prior to an acute event, may be warranted depending on the degree of coronary artery stenosis and symptoms ^1,4
• pericardial disease
  • acute pericarditis
    • supportive therapy with NSAIDs and colchicine is usually sufficient ^1,4
  • delayed pericarditis and constrictive pericarditis
    • supportive therapy may be given but is often not sufficient ^1,4
    • many patients require pericardiocentesis or even a pericardial window or pericardiectomy ^1,4
• valvulopathy
  • management depends on the severity of the valvulopathy, valve replacement may eventually be necessary ^1,4
• myocardium and conduction system disease
  • acute myocarditis
    • supportive therapy in an intensive care unit is often necessary ⁴
  • myocardial fibrosis (radiation-induced cardiomyopathy)
    • a similar pharmacological armamentarium to that used in heart failure may eventually be necessary ^1,4
  • arrhythmias
    • often no treatment is needed, however, anti-arrhythmic medications may be used ^1,4