Diagnostic Strategies for Early Recognition of Cancer Therapeutics-Related Cardiac Dysfunction

Abstract

Cardiovascular toxicity in the form of cardiac dysfunction continues to be an obstacle for patients with cancer. Survival and quality of life of cancer survivors are frequently affected by increased incidence of cardiovascular disease. The involvement of the cardiovascular system by primary or secondary malignancies, as well as its dysfunction secondary to the administration of antineoplastics, has led to the development of a new discipline called Cardio-Oncology, an exciting cardiology subspecialty with more questions than answers and as a result an enormous opportunity for research in the field. Multidisciplinary efforts have been focused on the prevention, diagnosis, and treatment of cancer therapeutics-related cardiovascular dysfunction (CTRCD). This review article will focus on the early diagnosis of left ventricular dysfunction associated with chemotherapy. Currently, the identification of cardiac toxicity associated with cancer treatment is the cornerstone for critical decisions regarding anticancer therapy and cardioprotective strategies. Its early detection, especially in subclinical phases, allows immediate intervention to prevent further impairment of the myocardium and other cardiovascular structures. The most significant published studies were selected for this revision, providing an updated document for the health professionals involved in the care of patients with cancer. We examined the current evidence and recommendations for biochemical and noninvasive diagnostic techniques, including their specific role for identification of CTRCD. Traditional and advanced imaging modalities, used alone or in combination with cardiovascular biomarkers, are essential for the recognition of cardiotoxicity during cancer therapy. Evolving basic and clinical research are focused on the development of more sensitive and specific diagnostic tools and for the recognition of cardiac toxicity.

Keywords: Cardiomyopathy; cardiotoxicity; chemotherapy.

Figure 1.

Progression of cancer therapeutics–related cardiac dysfunction. LV indicates left ventricular.

Figure 2.

Stages of CTRCD and its diagnosis. 2D indicates 2 dimensional; CMR, cardiac magnetic resonance; LV, left ventricular; MUGA, multiple-gated acquisition.

Figure 3.

Real-time 3-dimensional echocardiogram (3DE). Left ventricular volume measurements and ejection fraction calculation using semiautomated endocardial delineation. (A) Apical 4-chamber view, (B) apical 2-chamber view, (C) short axes view, and (D) 3-Dimensional reconstruction of the left ventricle for volumetricmeasurements. EDV indicates end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; SV, stroke volume. (Courtesy D. Spevack, MD)

Figure 4.

Global longitudinal strain assessed by speckle-tracking echocardiography. Measurements are obtained from the 3 apical views and averaged. Bull’s-eye plot is built from global and regional longitudinal systolic strain measurements representing the left ventricular myocardial function. (Courtesy J. Liu, MD)

Figure 5.

Bull’s-eye plot of a 60-year-old patient with breast cancer who received anthracycline-based chemotherapy followed by trastuzumab. Cardioprotective therapy was started due to early detection of abnormal global longitudinal strain (GLS) representing subclinical myocardial dysfunction. Almost complete normalization of speckle-tracking echocardiography parameters was noticed. (Courtesy J. Liu, MD)

Figure 6.

Evaluation and follow-up of patients receiving anthracyclines. 2DE indicates 2-dimensional echocardiography; 3DE, 3-dimensional echocardiography; CMR, cardiac magnetic resonance; CV, cardiovascular; ECG, electrocardiogram; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; LLN, Lower Limit of Normal. Source. Adapted from Plana et al. 2014;27:911–939 (Ref. 8).

Figure 7.

Evaluation and follow-up of patients receiving trastuzumab. 2DE indicates 2-dimensional echocardiography; 3DE, 3-dimensional echocardiography; CMR, cardiac magnetic resonance; CV, cardiovascular; ECG, electrocardiogram; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction; LLN, Lower Limit of Normal. Source. Adapted from Plana et al. 2014;27:911–939 (Ref. 8).