Essay on Echocardiography's Role in Chemotherapy Induced Cardiotoxicity

Literature Review

Echocardiography is the process of taking the images of the heart using two dimensional, three dimensional and doppler ultrasound. It is useful in monitoring the heart of patients with known heart diseases with the use of an echocardiogram. An echocardiogram is the equipment used to take the images of the heart. The equipment produces moving images of the heart in a painless test that uses sound waves.6 The images show the shape and size of the heart, and the functioning of the valves and heart chambers. One can use the images to assess the contraction of the heart muscles and blood flow. Echocardiography is used routinely for diagnosis on patients with known heart diseases and cancer patients undergoing chemotherapy. It can detect if there is fluid buildup in the pericardium, if the heart has blood clots inside, and if there are problems with the aorta. Cancer patients undergoing chemotherapy may develop cardiotoxicity. Echocardiography is useful in the diagnosis of chemotherapy induced cardiotoxicity.

Cardiotoxicity is a term used to refer to the to the toxicity that develops in the heart especially to patients that undergo chemotherapy. There have been recent developments in the treatments of cancers such as chemotherapy increasing patient outcomes and survival rates. Despite the developments, cancer patients morbidity and mortality are still under threat due to cancer therapeutics-related dysfunction.4 One of the dysfunctions, cardiotoxicity that is secondary to chemotherapy, affects the left ventricular ejection fraction, conduction disorders, onset heart failure, thrombotic events, hypertension, and cardiovascular ischemia. There are a number of chemotherapeutic drugs such as 5-flouroucil, cyclophosphamide, trastuzamab, and anthracycline that are known to cause cardiotoxicity.4 Some of the drugs are cause reversible while others cause irreversible heart dysfunctions. Anthracycline, for example, can cause irreversible heart dysfunctions while Trastusumabs effects can be reversed by stopping the dosage.

Detection of cardiac problems is necessary so as to determine methods for intervention. Early detection can be useful to prevent further damage to the left ventricular function. According to Manrique et al, early detection of chemotherapy induced cardiotoxicity is necessary so that the drugs combinations used can be modified to reduce the toxicity.4 Additionally, early detection can help to reduce left ventricular dysfunction. Enalapril is initiated to reduce cardiotoxicity and can be introduced as part of the chemotherapeutic treatment combinations. Early detection can help to reduce left ventricular dysfunction. Enalapril is a drug administered to reduce cardiotoxicity and can be introduced as portion of the chemotherapeutic treatment combinations. An endomyocardial biopsy is a substitute method used to detect anthracycline-induced cardiomyopathy, but is problematic due to its invasive nature. Endomyocardial biopsy is also unsuitable for the detection of chemotherapy induced toxicity because of the limited success of obtaining a biopsy containing a damaged myocardium and the quality of the sample biopsied and endomyocardial biopsy is an alternative method used to detect anthracycline-induced cardiomyopathy, but is problematic due to its invasive nature. Endomyocardial biopsy is also unsuitable for the detection of chemotherapy induced toxicity because of the limited success of obtaining a biopsy containing a damaged myocardium and the quality of the model biopsied. An MRI and nuclear angiography can also be used to detect cardiotoxicity, but echocardiography is the most suitable method used to detect chemotherapy induced toxicity.

The left ventricular ejection fraction is an indicator of prognosis and can be used to measure cardiac systolic function. People with left ventricular dysfunction are at a risk of contracting cardiac failure and ultimately death.1 The decline of the left ventricular ejection fraction is an indication of cardiotoxicity. Echocardiography routinely measures the left ventricular ejection function, and provides information on the diastolic and valvular function. It is a preferred diagnostic method because it is non-invasive and it does not expose the patient to radiation. 2D echocardiography is dependent on the quality of the images and the measurement variability for accuracy. Echocardiography can obtain accurate measurements of the left ventricular ejection fraction by having clear endocardial borders. The borders can be measured to trace the end-systolic volume and the end-diastolic volume. The use of contrast agents is helpful in this process to improve endocardial visualization and to reduce the variability of the inter-observer and the intra-observer.2 It helps to convert a most of the non-diagnostic studies into diagnostic studies.

Three-dimensional echocardiography is more accurate in measuring the left ventricular ejection function. It overcomes the limitations of 2D echocardiography such as the geometrical assumptions to measure the left ventricular volumes, and the inaccuracies of the left ventricular ejection function. 3D echocardiography used in real time is able to accurately measure the ejection fraction and assess the left ventricular volumes. Larsen and Mulvagh explain that the 3D echocardiography is more efficient in diagnosing chemotherapy induced cardiac toxicity compared to 2D echocardiography.3 With 3D echocardiography, there is faster relay of results and the variation of observers is also reduced. The results of 3D echocardiography also correlate to those taken by MRI machines and CT scans. 3D echocardiography is can monitor wall function of the heart and the assess the interval changes in the ejection fraction.2 A drop in the left ventricular ejection function may indicate subclinical cardiotoxicity, or there might be sufficient damage on the myocardium.

Apart from measurements of the left ventricular ejection function, chemotherapy induced toxicity can also be measured using diastolic parameters. Compared to left ventricular ejection fraction, diastolic parameters are a more sensitive and subtle in detecting cardiac dysfunction. Anthracyclines used in chemotherapy result in the abnormalities in the diastolic functions.5 Anthracyclines cause the ration of the early peak flow velocity and the atrial peak flow velocity to reduce. It also caused the declaration of the isovolumetric relaxation time, and the condition persists even after the treatment has stopped. Chemotherapy leads to isovolumetric relaxation weeks after chemotherapy that subsequently leads to systolic dysfunction.1 Cardiotoxicity is measured using the diastolic parameters with the use of the echocardiogram.

Stress testing can also be used to diagnose abnormalities of the functions of the left ventricle caused by chemotherapy. In patients undergoing chemotherapy, left ventricular ejection fraction develops abnormalities, and they are at a risk of developing congestive cardiac failure.5 Stress and exercise are seen to increase the abnormalities in the ejection fraction. Detection of chemotherapy induced toxicity can also be measured by using dobutamine stress echocardiography, but with conflicting results. Patients that seize the use of high dose of chemotherapy still experience myocardial contractile reserve, and a decline in the left ventricular ejection function. Patients using anthracyclines in high doses experience alteration of the fractional shortening, and this is observed using high dose dobutamine stress echocardiography. However, there are some studies that do not account for the alterations. For this reason, the dobutamine stress echocardiography is not preferred to diagnose chemotherapy induced cardiotoxicity.4 It is invasive in nature, produces inconclusive results, and it has limited repeatability. Nonetheless, prognostics can still be conducted using the exercise capacity to determine the overall risk of cardiovascular problems.

Chemotherapy induced cardiotoxicity can also be measured by assessing the myocardial deformation and deformation rate. Compared to assessment of the left ventricular ejection fraction, measuring the strain and stain rate can detect wall motion abnormalities and provide dimensional assessment of the myocardial process where the radial, longitudinal and circumferential functions are measured.6 Stress and strain levels have emerged as better measurement alternatives to the left ventricular ejection fraction and can detect dysfunctions of the heart in patients administered anthracyclines, trastuzumab, and taxanes. Patients under chemotherapy exhibit reductions in the longitudinal strain levels. Apart from the longitudinal strain, there are also radial regional systolic strain shortly after administering the first dose of anthracyclines. However, there are no observable changes in the left ventricular ejection fraction within the same time of diagnosis. Other patients, especially elderly women, experience limited or no changes in the left ventricular ejection fraction and also no observable changes in the systolic myocardial velocity. However, there were notable changes in the radial and longitudinal strain and strain rates during chemotherapy.2 The changes in the radial functions occur earlier in prominence compared to the longitudinal direction.

An echocardiogram can also be used to measure the torsion analysis in addition to using it to measure cardiotoxicity using the strain and strain rates. Patients that undergo chemotherapy exhibit twisting and untwisting rates, and deteriorations in torsions.4 There were no notable changes in the left ventricular ejection fraction and the left ventricular dimensions one month after chemotherapy. Strain and stress rates can be used to determine the long-term effects of anthracyclines. The longitudinal and radial myocardial stress levels can also be observed to reduce. However, the left ventricular ejection fraction remains the same. Changes in the strain rates indicate mortality and late cardiac dysfunction.3 Therefore, there are cases in patients where they do not exhibit any changes in the parameters in the diastolic function and left ventricular ejection fraction, but notable changes in the longitudinal strain from the baseline.

Chemotherapy induced toxicity is a serious complication that need constant monitoring to address its side effects. Echocardiography has a major role of diagnosing chemotherapy induced toxicity, and then intervention methods can be implemented accordingly. early detection can help to reduce left ventricular dysfunction. An MRI and nuclear angiography can also be used to detect cardiotoxicity, however, echocardiography is the most suitable method used to detect chemotherapy induced toxicity. Enalapril is used to reduce cardiotoxicity and can be another technique used to detect anthracycline-induced cardiomyopathy, but is problematic due to its invasive nature. Endomyocardial biopsy is also unsuitable for the detection of chemotherapy induced toxicity since of the limited success of obtaining a biopsy containing a damaged myocardium and the value of the sample biopsied. Measurement of the left ventricular ejection fraction and the radial and longitudinal strains can be integrated in the future to diagnose cardiac toxicity. Challenges such as poor image quality need to be overcome in the subject of echocardiography.

References

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Medicine. 2015:24 285295. (doi:10.1016/j. tcm.2014.07.003)

Kimmick G, Lenihan J, Sawyer B, Mayer L, Hershman L. Cardio-oncology: The clinical overlap of cancer and heart disease.

Larsen C, Mulvagh, S. Cardio-oncology: what you need to know now for clinical practice and echocar...