Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors

Jordan, Jennifer H.; Vasu, Sujethra; Morgan, Timothy M.; D’Agostino, Ralph B.; Meléndez, Giselle C.; Hamilton, Craig; Arai, Andrew E.; Liu, Songtao; Liu, Chia Ying; Lima, João A.C.; Bluemke, David A.; Burke, Gregory L.; Hundley, W. Gregory

doi:10.1161/circimaging.115.004325

Cited by 152 publications

(94 citation statements)

References 35 publications

(43 reference statements)

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“…The differential responses of CMR markers of cardiomyocyte atrophy and extra-cellular remodeling support further investigation of the role for CMR-based tissue characterization in anthracycline-based chemotherapy surveillance. Our study also extends the longitudinal observation of LV remodeling and dysfunction by CMR from approximately 3 months in 2 previous landmark studies (20,21) to up to 2 years after anthracyclines, which revealed an association between LV atrophy and peak cTnT response.…”

Section: Resultssupporting

confidence: 87%

“…Interstitial myocardial fibrosis is commonly observed in experimental models of AIC and is a functional marker of disease in patients: ECV is an independent risk factor for reduced exercise capacity (28), HF, and sudden death. Nevertheless, patient studies on the time course of fibrosis and hypertrophy development during anthracycline exposure remain limited (20,35). …”

Section: Resultsmentioning

confidence: 99%

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Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease

Souza

Quinaglia

Costa

et al. 2018

JACC: Cardiovascular Imaging

116

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OBJECTIVES The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. METHODS A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. RESULTS At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. CONCLUSIONS A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036) (J Am Coll Cardiol Img 2018;11:1045–55) © 2018 by the American College of Cardiology Foundation.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease

Souza

Quinaglia

Costa

et al. 2018

JACC: Cardiovascular Imaging

116

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“…In ischemic cardiomyopathy, delineation of the extent of infarction and the area of viable myocardium plays an important role in patient management and the assessment of long‐term prognosis 1, 2, 3, 4. Myocardial tissue characterization is also of value in the diagnosis and assessment of a number of nonischemic cardiomyopathies 5, 6, 7. In addition, scar‐imaging techniques are increasingly used in the preprocedural assessment of the underlying arrhythmic substrate for patients undergoing catheter ablation for ventricular arrhythmias,8 for which intraprocedural scar definition is performed using endocardial or epicardial voltage mapping 8, 9…”

Section: Introductionmentioning

confidence: 99%

“…A variety of imaging modalities and approaches have been used to assess myocardial injury, infiltration, and viability, most notably late gadolinium enhancement (LGE),1, 2, 3, 5, 6, 7 and positron emission tomography 10, 11, 12. LGE has emerged as a leading technique for tissue characterization of the myocardium; however, several issues complicate its use.…”

Section: Introductionmentioning

confidence: 99%

Myocardial Scar Delineation Using Diffusion Tensor Magnetic Resonance Tractography

Mekkaoui

Jackowski

Kostis

et al. 2018

JAHA

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BackgroundLate gadolinium enhancement (LGE) is the current standard for myocardial scar delineation. In this study, we introduce the tractographic propagation angle (PA), a metric of myofiber curvature (degrees/unit distance) derived from diffusion tensor imaging (DTI), and compare its use to LGE and invasive scar assessment by endocardial voltage mapping.Methods and Results DTI was performed on 7 healthy human volunteers, 5 patients with myocardial infarction, 6 normal mice, and 7 mice with myocardial infarction. LGE to delineate the infarct and border zones was performed with a 2‐dimensional inversion recovery gradient‐echo sequence. Ex vivo DTI was performed on 5 normal human and 5 normal sheep hearts. Endocardial electroanatomic mapping and subsequent ex vivo DTI was performed on 5 infarcted sheep hearts. PA in the normal human hearts varied smoothly and was generally <4. The mean PA in the infarct zone was significantly elevated (10.34±1.02 versus 4.05±0.45, P<0.05). Regions with a PA ≤4 consistently had a bipolar voltage ≥1.5 mV, whereas those with PA values between 4 and 10 had voltages between 0.5 and 1.5 mV. A PA threshold >4 was the most accurate DTI‐derived measure of infarct size and demonstrated the greatest correlation with LGE (r=0.95).ConclusionsWe found a strong correlation between infarct size by PA and LGE in both mice and humans. There was also an inverse relationship between PA values and endocardial voltage. The use of PA may enable myocardial scar delineation and characterization of arrhythmogenic substrate without the need for exogenous contrast agents.

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“…Left and right ventricular systolic functions determined by MRI were reduced at 24 months (but still within normal range) for the whole cohort. Furthermore, with T1 mapping, a promising technique to quantify morphologic tissue injuries, it was shown in cancer survivors (including BC patients) that interstitial/diffuse myocardial fibrosis was elevated 3 years after anthracycline-based chemotherapy independent of the underlying cancer or comorbidities, suggesting that imaging biomarkers of interstitial fibrosis are related to prior receipt of potentially cardiotoxic cancer treatment [28], that may also include ionizing radiation.…”

Section: Introductionmentioning

confidence: 99%

Early detection of cardiovascular changes after radiotherapy for breast cancer: Protocol for a European multicenter prospective cohort (MEDIRAD EARLY HEART Study) (Preprint)

Walker¹,

Crijns²,

Langendijk³

et al. 2018

Preprint

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1Background: Breast cancer (BC) is the most common cancer among women and radiotherapy (RT) plays a major role in its treatment. However, BC RT can lead to incidental irradiation of the heart, resulting in an increased risk of a variety of heart diseases arising many years after radiotherapy. Therefore, identifying BC patients with the highest-risk of radiation-induced cardiac complications is crucial for developing strategies for primary and secondary prevention, which may contribute to healthy ageing. There is still a need of precise knowledge on the relationship between radiation dose to specific cardiac structures and early subclinical cardiac changes and their occurrence in time that could finally lead to cardiac complications.

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Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors

Cited by 152 publications

References 35 publications

Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease

Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease

Myocardial Scar Delineation Using Diffusion Tensor Magnetic Resonance Tractography

Early detection of cardiovascular changes after radiotherapy for breast cancer: Protocol for a European multicenter prospective cohort (MEDIRAD EARLY HEART Study) (Preprint)

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