Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2022 May 31.
Published in final edited form as: Curr Cardiol Rep. 2018 Oct 26;20(12):142. doi: 10.1007/s11886-018-1075-7

The Role of Cardiovascular Magnetic Resonance for Surveillance of Cardiac Performance upon Receipt of Potentially Cardiotoxic Cancer Therapeutics

Amitabh Parashar 1,2, W Gregory Hundley 3,4,5,6,7
PMCID: PMC9154310  NIHMSID: NIHMS1803722  PMID: 30367282

Abstract

Purpose of Review

Advancements in cancer treatment have resulted in improved cancer-related survival and consequently an increase in the number of cancer survivors. Unfortunately, associated with this increase in cancer-related survivorship, cardiac events have occurred with increasing frequency in cancer survivors. Recognition that cancer survivors are at increased risk for cardiovascular (CV) morbidity has generated interest to develop cardiac imaging techniques that identify subclinical CV disease during receipt of potentially cardiotoxic cancer treatment. Since subclinical cardiovascular disease precedes future cardiac events, early recognition of subclinical CV disease during receipt of potentially cardiotoxic cancer treatment offers the opportunity to initiate strategies that prevent further evolution of subclinical CV disease as well as cardiac events.

Recent Findings

Cardiovascular magnetic resonance imaging (CMR) is an advanced imaging technique that identifies imaging markers of subclinical cardiovascular disease in patients receiving potentially cardiotoxic cancer treatment regimens. In this article, we review the use of CMR for identifying subclinical cardiac disease in patients receiving potentially cardiotoxic cancer treatment regimens.

Summary

The ability of contemporary CMR to accurately define cardiac anatomy, function, and tissue characteristics may represent a critical tool to assess patients with cancer.

Keywords: Cardiovascular magnetic resonance, CardioOncology

Background and Introduction

Over the last 20 years, there have been substantive advances in the diagnosis and treatment of various cancers such that today there are approximately 15.5 million cancer survivors in the USA. The number of cancer survivors is expected to increase to 20.3 million by 2026 [1]. Many patients surviving cancer are at increased risk of premature cardiac disease [2], both because of the overlap in risk factors for cancer and cardiovascular (CV) disease [3], and the potentially cardiotoxic effects of cancer treatment. Today, CV events including congestive heart failure, stroke, and myocardial ischemia and infarction are among the leading causes of premature morbidity and mortality among those surviving beyond 5 years from their initial diagnosis and treatment for breast cancer [2] or Hodgkin or non-Hodgkin lymphoma [3, 4]. Furthermore, congestive heart failure after cancer therapy incurs a 3.5-fold increased mortality risk compared with idiopathic cardiomyopathy, and for many cancer survivors, the risk of death from CV events after cancer treatment may exceed the risk of cancer recurrence [5, 6].

To reduce the incidence of CV events among cancer survivors, there is increasing interest to identify subclinical cardiac abnormalities that portend future CV events. In so doing, one could identify those suitable for CV interventions to prevent these future untoward CV events. To this end, cardiovascular magnetic resonance (CMR) provides highly accurate and reproducible assessments of regional cardiac function and measurement of right and left ventricular (LV) volumes, ejection fraction, and mass [7]. Furthermore, CMR is useful to assess factors that contribute to cardiac dysfunction including abnormalities of myocardial perfusion, tissue composition, and both ventricular pre- and afterload. Abnormalities of each of these measures are associated with CV events in other patient populations. In the following sections, we review data from studies utilizing CMR to identify abnormalities of sub- or clinical cardiac dysfunction associated with future CV events.

Assessment of Left and Right Ventricular Volumes, Mass, and Function

Cardiovascular magnetic resonance provides accurate and reproducible cine images of high spatial and temporal resolution in any desired plane without exposure to contrast agents or ionizing radiation [8-10]. The noninvasive assessment of cardiac function is both accurate [8, 9, 11] and reproducible in those with normal as well as abnormal ventricles [12, 13].

To acquire measures of right or left ventricular (RV or LV) volumes, mass, or ejection fraction, a series of contiguous tomographic slices are acquired in short axis planes oriented perpendicular to the long axis of the ventricles that encompass the entire left ventricle from the cardiac base to its apex. Ventricular volumes and mass are then calculated as the sum of the endocardial areas multiplied by the distance between the centers of each slice. Modern scanners utilizing their fast imaging can acquire a single cine in just one breath hold of about 8 to 10 s; allowing the whole stack of images to be acquired in 5 to 10 min. The volumes obtained by this method are therefore independent of geometric assumptions. Currently, both right and LV volumes are obtained using the same set of slices.

With transthoracic echocardiography, LV ejection fraction thresholds indicative of cardiotoxicity in those receiving cancer treatment have been defined by the American Society of Echocardiography as > 10% declines in LV ejection fraction to a value < 53% [14]. Drafts et al. [15] utilized CMR to determine when LV ejection fraction declines during receipt of potentially cardiotoxic chemotherapy. In this group’s study, LV ejection fraction was measured prior to and then at 1, 3, and 6 months after initiating anthracycline-based chemotherapy (Anth-bC). They demonstrated several important findings. First, they found that individuals with declines in LV ejection fraction 6 months after initiating Anth-bC often experienced a decline in LV ejection fraction 1 month after beginning treatment. Second, many of the declines in LV ejection fraction occurred commensurate with increases in LV end-systolic volume suggesting that Anth-bC promoted diminished myocardial contractility as the cause of the decline in LV ejection fraction.

Third, there were several individuals that experienced decline in LV ejection fraction after receipt of relatively low doses (< 150 mg/m2) of their respective Anth-bC regimen. This observation suggests that some individuals are susceptible to both subclinical and clinical myocardial injury at doses far lower than 450 to 550 mg/m2 of an anthracycline. Finally, no new infarcts or fibrosis by late gadolinium enhancement imaging were found during the study period. This suggests that new myocardial infarcts were not precipitated by the Anth-bC regimens that patients received [15].

In addition to the assessment of LV volumes and ejection fraction, from the same image acquisition, LV myocardial mass can be quantified during CMR. As with LV ejection fraction measures, LV mass assessments obtained with CMR are accurate and reproducible [16]. LV mass may decline—due to myocellular injury and death—in some patients receiving potentially cardiotoxic cancer treatments.

In a study by Nelian et al. [17] utilizing CMR, prognostic value of decreased LV mass was noted in 91 adult patients with reduced LVEF at a median of 88 months post-anthracycline therapy. During a median follow-up of 27 months, LV mass index was an independent predictor of a composite of cardiovascular death, appropriate implantable cardioverter defibrillator therapy, and admission for HF (hazard ratio, 0.89) despite medical therapy. An LV mass index of < 57 g/m2 had a sensitivity of 100% and specificity of 85% to predict adverse outcomes [17]. Future studies are needed to determine the association of LV mass changes with adverse outcomes in patients receiving treatment for cancer.

In a recent publication by Jordan et al. [18••], LV mass declines were found to occur early after receipt of Anth-bC. Interestingly, these declines occurred while both LV wall stress and afterload were elevated (Fig. 1). In other conditions, increases in LV wall stress and afterload, such as occurs with hypertension, serve as a stimulus for LV hypertrophy. After Anth-bC, it was noteworthy that the left ventricle did not respond to the increased wall stress and afterload by increasing its mass—rather it declined [18••].

Fig. 1.

Fig. 1

Open in a new tab

Six-month change in cardiovascular magnetic resonance (CMR)-derived left ventricular (LV) remodeling measurements after anthracycline-based chemotherapy (Anth-bC, orange), non-Anth-bC (purple) for breast cancer or hematologic malignancy and cancer-free comparators of similar age (white). Compared with cancer-free comparators, those receiving Anth-bC had a significant decrease in LV ejection fraction (LVEF; a; P < 0.01) and LV myocardial mass (b; P = 0.03) that occurred concurrently with increased end-systolic wall stress index (c; P < 0.01) and reduced ventricular-arterial coupling (d; P < 0.01). Changes among patients with cancer who received non-Anth-bC were not statistically different than those observed in noncancer comparators (P > 0.15 for all). Data shown as mean ± SEM.*P < 0.05 for change from baseline. †P < 0.05 vs change in controls. (With permission from Jordan and Hundley [18••])

A second important observation in this study related to an association of LV mass decline with heart failure sympto matology. This study is the first to demonstrate that early (within 6 month) declines in LV mass are associated with symptoms consistent with the presence of heart failure (Fig. 2). This relationship was present after accounting for measurement of LV ejection fraction and raises the possibility that algorithms may want to assess LV mass or other factors in addition to LV ejection fraction when surveying patients for evidence of cardiac injury upon receipt of potentially cardiotoxic cancer treatments.

Fig. 2.

Fig. 2

Open in a new tab

Associations of cardiovascular magnetic resonance-derived changes in left ventricular (LV) remodeling with worsening Minnesota Living With Heart Failure Questionnaire in patients with cancer treated with anthracyclines. Subclinical declines in LV ejection fraction (LVEF; a) were not associated with worsening of total Minnesota Living With Heart Failure Questionnaire (MLHFQ) score (P = 0.45). Instead, atrophic remodeling (reduced myocardial mass; b) was associated with worsening total MLHFQ score (P < 0.01) 6 months after initiation of cancer treatment. Correlation of variables in a and b with P values for model adjusted for baseline MLHFQ score. (With permission from Jordan and Hundley [18••])

Left ventricular mass by CMR has been examined in those previously treated in childhood for cancer. Left ventricular mass ≥ 2 standard deviations below the mean normative value has been reported in 48% of childhood cancer survivors [44].

Assessment of Left Ventricular Strain

Early reduction in LV global longitudinal myocardial strain or strain rate using transthoracic echocardiography is associated with future declines in LV ejection fraction in patients receiving potentially cardiotoxic chemotherapy [20, 21]. To date, the majority of CMR-based techniques used to assess LV strain in those treated for cancer involve assessment of LV mean mid-wall circumferential strain. Using this method, a decline of mid-wall circumferential strain at 1 month of therapy in 53 asymptomatic patients treated with Anth-bC remained reduced at 6 months [18••, 20]. Another possible method to calculate LV myocardial strain incorporates harmonic phase magnetic resonance imaging (HARP-MRI). This pulse sequence has been used to serially follow chemotherapy patients at high risk of developing cardiac dysfunction [22].

Jolly et al. assessed myocardial strain through the analysis of cine white blood images [23••]. This technique is advantageous because it does not incorporate special tagged or harmonic phase images; rather, the analysis is performed from the same images used to measure LV volumes, mass, and ejection fraction. Using a slice acquired at the middle papillary muscle level of the LV short axis as identified in the four-chamber view, mean mid-wall circumferential strain was assessed before and 3 months after receipt of potentially cardiotoxic chemotherapy. Participants (n = 72) averaged 54 ± 14 years in age and were receiving treatment for breast cancer, lymphoma, or sarcoma. Overall, mean mid-wall left ventricular myocardial strain deteriorated from −18.8 ± 2.9 to −17.6 ± 3.1 at 3 months, p = 0.001. There was a strong correlation between cine myocardial strain and left ventricular ejection fraction: r = −0.61; p = 0.0001. Future studies are needed to assess the role of CMR strain for predicting adverse cardiac outcomes in patients receiving potentially cardiotoxic chemotherapy.

This particular technique has the advantage of assessing myocardial strain for the cine images and not requiring a tagged imaging acquisition nor an analysis package specific to myocardial tissue tagging [23••].

At present, long-term follow-up studies of CMR-derived measures of global longitudinal strain among patients receiving potentially cardiotoxic chemotherapy have not been performed. Three ongoing studies (R01CA167821, R01CA199167, R01HL118740) funded by the National Institutes of Health will address this issue.

Assessment of LV Myocardial Tissue with T1 Mapping to Understand the Etiology of Left Ventricular Dysfunction

T1 mapping measures the longitudinal or spin-lattice relaxation time, which is determined by how rapidly protons reequilibrate their spins after being excited by a radiofrequency pulse [19]. Cancer therapy-induced myocardial injury may promote toxic injury to the myocardium through multiple mechanisms [24] that promote changes in LV myocardial T1. Early studies using T1-weighted CMR imaging approaches demonstrated increased myocardial gadolinium uptake after a single course of chemotherapy in individuals who later developed LV dysfunction, [25]. A limitation of these approaches relates to the fact that T1 is not calculated from the data. Additionally, other issues impacting signal intensity, for example, distance from the target of interest in the images to the surface coils, can impact the results.

To address these limitations, investigators have begun utilizing T1 mapping to evaluate the LV myocardium during and after receipt of potentially cardiotoxic cancer therapy. Mapping allows one to measure the T1 values within each voxel comprising the LV myocardium. Jordan et al. studied 37 individuals with breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n = 37) or nonanthracycline-based (n = 17) chemotherapy 2.8 ± 1.3 years earlier and compared their evaluations with 236 cancer-free participants. The study participants were drawn from two NIH-funded studies who had their CMR examination done between 2010 and 2012.

Myocardial native T1 was noted to be elevated in pre- and post-treatment cancer participants (1058 ± 7 and 1040 ± 7 ms, respectively) compared to controls without cancer (965 ± 3 ms, p < 0.0001 for both) Fig. 3 [26]. This finding was interesting and merits further study to determine if the presence of cancer in and of itself is associated with increases in myocardial T1. She also found that age-adjusted myocardial extracellular volume fraction or extracellular volume fraction (ECV) was elevated in patients that had previously received Anth-bC at 30.4 ± 0.7%, compared to individuals without cancer at 26.9 ± 0.2% or individuals prior to receipt of cancer treatment at 27.8 ± 0.7%, p < 0.0001 and p < 0.01, respectively [26]. Myocardial ECV is calculated from both the pre- and postgadolinium contrast T1 maps and represents the percentage of material within the space between the myocytes relative to the entire myocardial volume.

Fig. 3.

Fig. 3

Open in a new tab

T1 and ECV map images. Representative left ventricular (LV) short axis native T1 (top row) and extracellular volume (ECV, bottom row) maps are shown in similarly-aged participants. The LV and right ventricular (RV) blood pool cavities are noted. On each image, the color of pixels in the images (color scales on left) identifies the native T1 (milliseconds) and ECV (%). Insets on the ECV maps demonstrate the change in color intensity within the anterolateral wall of each ventricle. As shown, ECV is elevated in the cancer survivor previously treated with anthracycline-based chemotherapy. (With permission from Jordan et al. [26])

This study also showed that LV myocardial ECV measured with CMR was abnormally increased even 3 years after receipt of anthracycline-based chemotherapy above and beyond noted in the presence of cancer prior to treatment [26]. This elevation in ECV persisted after accounting for pre-existing CV comorbidities associated with subclinical fibrosis development. More importantly, increased subclinical myocardial fibrosis, as manifest by ECV elevations, coincided with decreases in left ventricular ejection fraction and myocardial mass in adult cancer survivors 3 years after receiving Anth-bC [26].

Published data show that ECV is increased in mid- and long-time survivors of anthracycline therapy when compared with normal control subjects. These changes correlate with cumulative dose, impairment of peak oxygen consumption [27], and parameters of diastolic dysfunction [28].

An interesting recently published manuscript and accompanying editorial [29, 30] raises important questions regarding the use of ECV assessments in patients that received potentially cardiotoxic chemotherapy. The ECV calculation involves measurement of a ratio of the volume of tissue within the myocardial interstitial space/the total volume of the LV myocardium. Therefore, an increase in LV myocardial ECV may result from an increase in the volume appropriated to the interstitial space, or conversely a decrease in myocyte size or number that diminishes total LV myocardial volume.

De Souza et al. [29] used properties related to the clearance of gadolinium to determine if Anth-bC-associated ECV increases were related to a decrease in myocellular size, an increase in the interstitial space, or both. Among 27 women with breast cancer receiving Anth-bC, they found that LV ejection fraction declined along with decreases in LV mass and increases in ECV were related to cardiomyocyte atrophy versus increases in LV myocardial interstitial fibrosis. This raises important considerations for those receiving Anth-bC or for other medical conditions that may experience an increase in ECV. Not all increases in ECV may necessarily be related to increases in LV myocardial interstitial space components.

Monitoring Response to Cardioprotective Therapy with CMR

Cardiovascular magnetic resonance has been used in clinical trials of prophylactic cardioprotective medications in patients receiving cancer therapy or in monitoring the response to therapy in patients with established cardiomyopathy. A recent randomized controlled study of β-blockers and ACE inhibitors in 90 patients with hematologic malignancies receiving Anth-bC illustrated a 3.4% drop of LVEF in the control group and no change in the treatment group at 6 months [31].

Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research (MANTICORE)-101 randomized placebo-controlled trial of an ACE inhibitor or β-blocker in 159 women with breast cancer receiving trastuzumab used CMR-based change in LV end-diastolic volume at 12 months as the primary outcome and LVEF as the secondary outcome [32]. Results of this study demonstrated that prophylactic treatment with perindopril or bisoprolol prevented trastuzumab-mediated declines in LV ejection fraction. Additionally, these cardioprotective medications avoided associated interruptions in trastuzumab therapy and delays in adjuvant therapy initiation [33] and interruptions in hormonal therapy [34, 35].

The randomized placebo-controlled Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA) trial of angiotensin receptor blocker or β-blocker in 120 women with breast cancer receiving epirubicin-containing chemotherapy and trastuzumab as indicated also chose change in LV ejection fraction by CMR as the primary end point [35]. Using serial CMR for assessment of left ventricular function, PRADA revealed that low-to-moderate doses of anthracyclines with or without trastuzumab or radiation are associated with a numerically modest, but significant reduction in LVEF (−2.6%); these changes in LVEF were unlikely to have been reliably detected by echocardiography (which typically identifies LVEF changes of larger magnitude like 10%) [14, 45]. The PRADA results demonstrated that concomitant therapy with candesartan alleviated the decline in LVEF (−0.8%) when compared to those in the placebo group. No effect of metoprolol on the overall decline in LVEF was observed in this study.

Potential Use of CMR to Detect Cancer Therapy-Associated Myocarditis

Subjects receiving certain interleukin-based immunotherapy for certain cancers are at risk for developing an inflammatory cardiomyopathy or myocarditis. Relatively limited data are available utilizing CMR in this situation. In a study of 14 individuals with an inflammatory cardiomyopathy compared to 14 gender- and age-matched healthy control subjects, abnormalities of myocardial tissue characteristics were observed in those with myocarditis compared to the control population [37]. In a study by Ingkanisorn [36], the appearance of myocarditis associated with high doses of interleukin 2 in 7 patients was similar in nature compared to 14 individuals that experienced a community-acquired myocarditis. Further studies are needed to evaluate the utility of CMR for identifying myocarditis in patients suspected of developing an autoimmune process as a result of treatment for cancer.

Identification of Amyloid Deposition in Myocardium in Patients with Multiple Myeloma

Amyloid proteins may accumulate within the heart muscle in patients with multiple myeloma [38]. Light chain amyloid has specific abnormalities observed with CMR, particularly after the administration of Gd contrast. One of the most pathognomonic signs is difficulty in nulling LV myocardium when extensive amyloid light chain is present [39, 40]. Additionally, subendocardial late enhancement can be appreciated in this patient population [41, 42].

Among 251 individuals with a plasma cell dyscrasia who underwent CMR with a mean age of 63 ± 10 years, the presence of late Gd enhancement associated with LV intramyocardial amyloid independently predicted mortality even after accounting for other factors associated with cardiovascular disease, including the presence of coronary artery disease, age, and gender [38].

In another study of 130 subjects with cardiac amyloid, unusual patterns of LV hypertrophy have also been appreciated [39]. Asymmetric LVH has been found in up to 2/3 of individuals with transthyretin-related (TTR) and light chain (AL) amyloid [39].

Cardiac MRI LGE and T1 mapping characteristics for the AL and TTR amyloidosis exhibit mild differences but in general cannot completely distinguish the two conditions. Prior studies have demonstrated that the pattern of LGE in ATTR amyloidosis may differ from that in AL amyloidosis. The pattern of LGE in cardiac ATTR amyloidosis may exhibit more of a base-apex gradient that correlates with echocardiographic studies using strain analysis, which have reported reduced basal systolic longitudinal and radial strain (“apical sparing”) in cardiac amyloidosis [41, 42]. Patients with systemic AL amyloidosis may exhibit increased noncontrast T1 relaxation times in the myocardium in an LV endocardially based pattern. Among amyloid patients with overt cardiac involvement, the T1 increases are more pronounced than in patients with aortic stenosis and a similar degree of ventricular wall thickening. Furthermore, noncontrast T1 relaxation times correlate well with markers of systolic and diastolic dysfunction, indicating that the elevation in myocardial T1 likely reflects the severity of cardiac involvement. Thus, T1 mapping may have potential as a valuable method for diagnosing and quantifying cardiac involvement in systemic AL amyloidosis [43].

Conclusion

The ability of contemporary CMR to accurately define cardiac anatomy, function, and tissue characteristics may represent a critical tool to assess patients with cancer. CMR is valuable to identify the presence and cause of LV dysfunction among patients receiving treatment for cancer. A combination of CMR functional and tissue characterization methods (incorporating T1, T2, late gadolinium enhancement, strain and stress perfusion) can be used to distinguish (A) LV dysfunction possibly due to primary cardiomyocyte abnormalities associated with the administration of chemotherapy or consequences as a result of the cancer itself; (B) the presence of infiltrative disorders, such as amyloidosis; (C) myocarditis due to infectious or autoimmune causes; and (D) elevations of LV myocardial ECV that may indicate and increase in LV interstitial fibrosis or a decrease in LV myocyte volume or size. Ongoing studies will help us determine to what extent CMR-based changes with cancer treatment can help guide therapeutic decisions to detect and/or prevent cancer therapy-related cardiac toxicity.

Funding Information

This research was supported in part by National Institutes of Health grants R01CA167821, R01CA199167, R01HL118740.

Footnotes

Conflict of Interest Amitabh Parashar and W. Gregory Hundley declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as:

• Of importance

•• Of major importance

  • 1.https://www.cancer.gov/about-Cancer/understanding/statistics). Access 5 June 2018. [Google Scholar]
  • 2.Hooning MJ, Botma A, Aleman BM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99:365–75. [DOI] [PubMed] [Google Scholar]
  • 3.Swerdlow AJ, Higgins CD, Smith P, et al. Myocardial infarction mortality risk after treatment for Hodgkin’s disease: a collaborative British cohort study J Natl Cancer Inst. 2007;99:206–14. [DOI] [PubMed] [Google Scholar]
  • 4.Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–5. [DOI] [PubMed] [Google Scholar]
  • 5.Carver JR, et al. ASCO Cancer Survivorship Expert Panel. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25:3991–4008. [DOI] [PubMed] [Google Scholar]
  • 6.Silber JH, et al. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol. 2004;22:820–8. [DOI] [PubMed] [Google Scholar]
  • 7.Mor-Avi V, Jenkins C, Kuhl HP, et al. Real-time 3-dimensional echocardiographic quantification of left ventricular volumes: multicenter study for validation with magnetic resonance imaging and investigation of sources of error. J Am Coll Cardiol Img. 2008;1:413–23. [Google Scholar]
  • 8.Natori S, Lai S, Finn JP, et al. Cardiovascular function in multiethnic study of atherosclerosis: normal values by age, sex, and ethnicity. AJR Am J Roentgenol. 2006;186:S357–65. [DOI] [PubMed] [Google Scholar]
  • 9.Katz J, Millikem MC, Stray-Gunderson J, et al. Estimation of human myocardial mass with MR imaging. Radiology. 1988;169:495–8. [DOI] [PubMed] [Google Scholar]
  • 10.Katz J, Whang J, Boxt LM, Barst RJ. Estimation of right ventricular mass in normal subjects and in patients with primary pulmonary hypertension by nuclear magnetic resonance imaging. J Am Coll Cardiol. 1993;21:1475–81. [DOI] [PubMed] [Google Scholar]
  • 11.Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–21. [DOI] [PubMed] [Google Scholar]
  • 12.Semelka RC, Tomei E, Wagner S, et al. Interstudy reproducibility of dimensional and functional measurements between cine magnetic resonance imaging studies in the morphologically abnormal left ventricle. Am Heart J. 1990;119:1367–73. [DOI] [PubMed] [Google Scholar]
  • 13.Pattynama PM, Lamb HJ, van der Velde EA, van der Wall EE, De Roos A. Left ventricular measurements with cine and spin-echo MR imaging: a study of reproducibility with variance component analysis. Radiology. 1993;187:261–8. [DOI] [PubMed] [Google Scholar]
  • 14.Plana JC, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014;27:911–39. [DOI] [PubMed] [Google Scholar]
  • 15.Drafts BC, Twomley KM, D’Agostino R Jr, Lawrence J, Avis N, Ellis LR, et al. Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease. J Am Coll Cardiol Cardiovasc Imaging. 2013;6:877–85. [Google Scholar]
  • 16.Grothues F, Smith GC, Moon JCC, et al. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol. 2002;90:29–34. [DOI] [PubMed] [Google Scholar]
  • 17.Neilan TG, Coelho-Filho OR, Pena-Herrera D, Shah RV, Jerosch-Herold M, Francis SA, et al. Left ventricular mass in patients with a cardiomyopathy after treatment with anthracyclines. Am J Cardiol. 2012;110:1679–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.••. Jordan J, Hundley WG. Left ventricular mass change after anthracycline chemotherapy. Circ Heart Fail. 2018;11(7):e004560. This study documented a decline in LV mass with Anth B chemotherapy and association of LV mass decline with heart failure symptomatology.
  • 19.Ridgway JP. Cardiovascular magnetic resonance physics for clinicians: part I. J Cardiovasc Magn Reson. 2010;12:71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57:2263–70. [DOI] [PubMed] [Google Scholar]
  • 21.Negishi K, Negishi T, Hare JL, Haluska BA, Plana JC, Marwick TH. Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr. 2013;26:493–8. [DOI] [PubMed] [Google Scholar]
  • 22.Sampath S, Derbyshire JA, Atalar E, Osman NF, Prince JL. Real-time imaging of two-dimensional cardiac strain using a harmonic phase magnetic resonance imaging (HARP-MRI) pulse sequence. Magn Reson Med. 2003;50:154–63. [DOI] [PubMed] [Google Scholar]
  • 23.••. Jolly MP, Jordan JH, Meléndez GC, Mcneal GR, D’Agostino RB, Hundley WG. Automated assessments of circumferential strain from cine CMR correlate with LVEF declines in cancer patients early after receipt of cardio- toxic chemotherapy. J Cardiovasc Magn Reson. 2017;19(1):59–62 This study found a strong correlation between cine myocardial strain and left ventricular ejection fraction: r = −0.61; p = 0.0001.
  • 24.Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18(11):1639–42. [DOI] [PubMed] [Google Scholar]
  • 25.Wassmuth R, Lentzsch S, Erdbruegger U, et al. Subclinical cardiotoxic effects of anthracyclines as assessed by magnetic resonance imaging—a pilot study. Am Heart J. 2001;141(6):1007–13. [DOI] [PubMed] [Google Scholar]
  • 26.Jordan JH, Vasu S, Morgan TM, D’Agostino RB Jr, Meléndez GC, Hamilton CA, et al. Anthracycline-associated T1 mapping characteristics are elevated independent of the presence of cardiovascular comorbidities in cancer survivors. Circ Cardiovasc Imaging. 2016;9(8). 10.1161/CIRCIMAGING.115.004325). [DOI] [Google Scholar]
  • 27.Tham EB, Haykowsky MJ, Chow K, et al. Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling. J Cardiovasc Magn Reson. 2013;15:48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Neilan TG, Coelho-Filho OR, Shah RV, et al. Myocardial extracellular volume by cardiac magnetic resonance imaging in patients treated with anthracycline-based chemotherapy. Am J Cardiol. 2013;111(5):717–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.de Souza TF, Silva TQAC, Osorio Costa F, et al. Anthracycline therapy is associated with cardiomyocyte atrophy and preclinical manifestations of heart disease. J Am Coll Cardiol Img. 2018;1045–55. [Google Scholar]
  • 30.Hundley WG, Jordan JH. When left ventricular extracellular volume fraction changes after anthracyclines: is it due to a change in the numerator, denominator, or both? J Am Coll Cardiol Img. 2018;11:1056–8. [Google Scholar]
  • 31.Bosch X, Rovira M, Sitges M, Domènech A, Ortiz-Pérez JT, de Caralt TM, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (prevention of left ventricular dysfunction with Enalapril and caRvedilolin patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013;61:2355–62. [DOI] [PubMed] [Google Scholar]
  • 32.Pituskin E, Haykowsky M, Mackey JR, Thompson RB, Ezekowitz J, Koshman S, et al. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101–Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI BMC Cancer. 2011;11:318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Chavez-MacGregor M, Clarke CA, Lichtensz-tajn DY, et al. Delayed initiation of adjuvant chemo-therapy among patients with breast cancer. JAMA Oncol. 2016;2:322–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Hsieh KP, Chen LC, Cheung KL, et al. Interruption and nonadherence to long-term adjuvant hormone therapy is associated with adverse survival outcome of breast cancer women—an Asian population-based study. PLoS One. 9:e87027 2014. have each been associated with lower breast cancer survival. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Heck SL, Gulati G, Ree AH, Schulz-Menger J, Gravdehaug B, Røsjø H, et al. Rationale and design of the prevention of cardiac dysfunction during an Adjuvant Breast Cancer Therapy (PRADA) trial. Cardiology. 2012;123:240–7. [DOI] [PubMed] [Google Scholar]
  • 36.Ingkanisorn WP, Paterson DI, Calvo KR, Rosing D, Schwart zentruber D, Fuisz A, et al. Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: similarities to community acquired myocarditis. J Cardiovasc Magn Reson. 2006;8(2):353–60. [DOI] [PubMed] [Google Scholar]
  • 37.Diederichsen LP, Simonsen JA, Diederichsen AC, Kim WY, Hvidsten S, Hougaard M, et al. Cardiac abnormalities assessed by non-invasive techniques in patients with newly diagnosed idiopathic inflammatory myopathies. Clin Exp Rheumatol. 2015;33(5):706–14. [PubMed] [Google Scholar]
  • 38.Bhatti S, Watts E, Syed F, Vallurupalli S, Pandey T, Jambekar K, et al. Clinical and prognostic utility of cardiovascular magnetic resonance imaging in myeloma patients with suspected cardiac amyloidosis. Eur Heart J Cardiovasc Imaging. 2016;17(9):970–7. [DOI] [PubMed] [Google Scholar]
  • 39.Pozo E, Kanwar A, Deochand R, Castellano JM, Naib T, Pazos-López P, et al. Cardiac magnetic resonance evaluation of left ventricular remodeling distribution in cardiac amyloidosis. Heart. 2014;100(21):1688–95. [DOI] [PubMed] [Google Scholar]
  • 40.Pozo E, Castellano JM, Kanwar A, et al. Myocardial amyloid quantification with look-locker magnetic resonance sequence in cardiac amyloidosis. Diagnostic accuracy in clinical practice and histological validation. J Card Fail. 2017;08:445–53. [Google Scholar]
  • 41.Phelan D, Collier P, Thavendiranathan P, et al. Relative “apical sparing” of longitudinal strain using two-dimensional speckle tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98:1442–8. [DOI] [PubMed] [Google Scholar]
  • 42.Dungu JN, Valencia O, Pinney JH, Gibbs SDJ, Rowczenio D, Gilbertson JA, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC Cardiovasc Imaging. 2014;7(2):133–42. [DOI] [PubMed] [Google Scholar]
  • 43.Karamitsos TD, Piechnik SK, Banypersad SM, Fontana M, Ntusi NB, Ferreira VM, et al. Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. JACC Cardiovasc Imaging. 2013;6(4):488–97. [DOI] [PubMed] [Google Scholar]
  • 44.Armstrong GT, Plana JC, Zhang N, Srivastava D, Green DM, Ness KK, et al. Screening adult survivors of childhood cancer for cardiomyopathy: comparison of echocardiography and cardiac magnetic resonance imaging. J Clin Oncol. 2012;30:2876–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Thavendiranathan P, Grant AD, Negishi T, Plana JC, Popovic ZB, Marwick TH. Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: application to patients undergoing cancer chemotherapy. J Am Coll Cardiol. 2013;61:77–84. [DOI] [PubMed] [Google Scholar]

RESOURCES