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Late Effects



Assessment and Diagnosis


The following reference documents are useful information sources:

Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: Diagnosis and management

Is it heart failure and what should I do?

To assess any patient with suspected cardiomyopathy, the most important initial investigation is:

Detailed clinical history including:

  • Cardiac symptoms:15
    • dyspnea
    • chest pain
    • palpitations
    • changes in exercise tolerance
    • functional limitations/capacity
  • Cerebrovascular disease symptoms
    • transient neurologic (sensory or motor) symptoms suggestive of TIA
  • Review of Cardiac Risk Factors:
    • Hypertension
    • Hyperlipidemia
    • Diabetes
    • Smoking
    • Family history of heart disease
  • Review of social factors
    • Alcohol
    • Illicit drug use (cocaine, crystal meth)
  • Background history
    • Diagnosis and extent of previous cancer
    • Total cumulative dose of anthracycline and other chemotherapy given
    • Radiotherapy
      • Total dose
      • Fractionation
      • Dates given
      • Region of body treated (how much of the heart was included in the RT volume?)
      • Was concurrent chemotherapy given with RT to the chest?
  • Any previous evaluation of cardiac function

Physical Examination:

  • Weight
  • Vital Signs
  • Volume Status
  • Cardiac/Pulmonary Exam


Evaluation of Cardiac Function:

Initial Investigations

Chest x-ray


Baseline 12-lead electrocardiogram is recommended at the end of therapy

Not useful for the detection of early toxicity. Changes in the ST-T segment and QRS complex on electrocardiography are frequently late in the course of cardiac toxicity14.

ECGs are useful in children as there are non invasive and when a decrease in ejection fraction or fractional shortening is found, it represents potential anthracycline cardiotoxicity14.

Prolongation of QTc:

  • Reported in long-term survivors after anthracycline Rx22
  • Patients with prolonged QTc should be counselled  about the use of medications which can cause further prolongation of QTc such as:
    • tricyclic antidepressants
    • macrolide antibiotics
    • antifungal agents
    • metronidazole
    • antipsychotics
    • antiarrhythmics

A detailed evaluation by a cardiologist should be considered for patients with prolonged QTc and subclinical left-ventricular dysfunction.


BNP (Brain natriuretic peptide) and ANP (atrial natriuretic peptide)

Elevated levels of serum BNP have been found in asymptomatic individuals who have been treated with anthracyclines18

Bone marrow transplant patients and patients treated with cardiac irradiation had the highest levels of ANP19.

Preliminary results from one study suggest that N-terminal pro B style BNP may help in identifying cardiac stress before irreversible damage occurs in children receiving anthracyclines20


HsCRP (high sensitivity C reactive protein)

HsCRP is also an independent predictor of outcome in some studies of adults with ischemic and non-ischemic cardiomyopathy and may be an important indicator of overall cardiovascular health during and after treatment20.

Transthoracic echocardiography (TTE)

  • Non-invasive
  • Evaluates possible structural changes in valves and pericardium secondary to radiotherapy.
  • Assesses diastolic function
  • In large patients, TTE echocardiogram may be technically difficult and of poor quality and accuracy
  • Trans esophageal echocardiography (TEE)  Tissue Doppler imaging is a non-invasive echocardiographic technique that assesses myocardial contractility. It has been studied predominantly in adults with ischemic heart disease. Studies of tissue Doppler imaging among cancer survivors are limited.

Echocardiogram is often the first investigation to measure subclinical deterioration

  • FS (fractional shortening)
    • lower limit of normal for FS is usually 28%.
  • EF (ejection fraction)
    • The lower limit of normal EF varies between 50% and 55%.
  • velocity of fiber shortening corrected for heart rate
  • stress velocity index
  • end-systolic wall stress
  • posterior wall thickness and left ventricular dimension

Diastolic function should be indirectly measured by measuring the ratio of peak early filling to peak late filling of the left ventricle during diastole on Doppler echocardiography.

Radionuclide ventriculography

  • Peak flow rate of filling assesses diastolic function
  • The left-ventricular ejection fraction (EF) measured by radionuclide angiocardiography has excellent reproducibility and accuracy which measures systolic function
  • Less operator dependent than echocardiography.

The FS obtained by echocardiogram and EF obtained by radionuclide ventriculography are not directly convertible.


MRI can be used for assessment of cardiac dysfunction after anthracyclines, but there is no evidence to suggest this should be used routinely.

Exercise stress testing

  • Can show abnormalities not seen on resting studies21.
  • Both anthracycline-induced cardiomyopathy and RT-induced cardiovascular disease are associated with exercise-associated decompensation.
  • Signs of ischemia and significant coronary artery disease are common on stress imaging of adult survivors of Hodgkin lymphoma (HL) treated with mediastinal radiation to 35 Gy2
  • Stress echocardiography and radionuclide perfusion imaging can identify asymptomatic individuals at high risk for acute myocardial infarction or sudden death.
  • Exercise stress test with or without imaging (echocardiography or radionuclide angiocardiography) is a useful screening tool21.


  • In patients with a history of previous mediastinal RT and symptoms suggestive of cardiopulmonary dysfunction (not due to poor systolic function or other causes), measure:
    • maximum oxygen consumption on exercise testing
    • pulmonary function tests


Screening is recommended for several decades after completion of therapy


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