Risk stratification of cardiac metastases using late gadolinium enhancement cardiovascular magnetic resonance: prognostic impact of hypo-enhancement evidenced tumor avascularity

Abstract

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is widely used to identify cardiac neoplasms, for which diagnosis is predicated on enhancement stemming from lesion vascularity: Impact of contrast-enhancement pattern on clinical outcomes is unknown. The objective of this study was to determine whether cardiac metastasis (C_MET) enhancement pattern on LGE-CMR impacts prognosis, with focus on heterogeneous lesion enhancement as a marker of tumor avascularity.

Methods: Advanced (stage IV) systemic cancer patients with and without C_MET matched (1:1) by cancer etiology underwent a standardized CMR protocol. C_MET was identified via established LGE-CMR criteria based on lesion enhancement; enhancement pattern was further classified as heterogeneous (enhancing and non-enhancing components) or diffuse and assessed via quantitative (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR)) analyses. Embolic events and mortality were tested in relation to lesion location and contrast-enhancement pattern.

Results: 224 patients were studied, including 112 patients with C_MET and unaffected (C_MET -) controls matched for systemic cancer etiology/stage. C_MET enhancement pattern varied (53% heterogeneous, 47% diffuse). Quantitative analyses were consistent with lesion classification; CNR was higher and SNR lower in heterogeneously enhancing C_MET (p < 0.001)-paralleled by larger size based on linear dimensions (p < 0.05). Contrast-enhancement pattern did not vary based on lesion location (p = NS). Embolic events were similar between patients with diffuse and heterogeneous lesions (p = NS) but varied by location: Patients with right-sided lesions had threefold more pulmonary emboli (20% vs. 6%, p = 0.02); those with left-sided lesions had lower rates equivalent to controls (4% vs. 5%, p = 1.00). Mortality was higher among patients with C_MET (hazard ratio [HR] = 1.64 [CI 1.17-2.29], p = 0.004) compared to controls, but varied by contrast-enhancement pattern: Diffusely enhancing C_MET had equivalent mortality to controls (p = 0.21) whereas prognosis was worse with heterogeneous C_MET (p = 0.005) and more strongly predicted by heterogeneous enhancement (HR = 1.97 [CI 1.23-3.15], p = 0.005) than lesion size (HR = 1.11 per 10 cm [CI 0.53-2.33], p = 0.79).

Conclusions: Contrast-enhancement pattern and location of C_MET on CMR impacts prognosis. Embolic events vary by C_MET location, with likelihood of PE greatest with right-sided lesions. Heterogeneous enhancement-a marker of tumor avascularity on LGE-CMR-is a novel marker of increased mortality risk.

Keywords: Cardiac neoplasm; Cardio-oncology; Cardiovascular magnetic resonance.

Fig. 1

Study design. Overall schematic of multicenter enrollment as well as standardized cardiovascular magnetic resonance (CMR) acquisition and analysis. Note that both enrolling sites employed a tailored CMR protocol for assessment of C_MET, inclusive dedicated long inversion time (TI) late gadolinium enhancement (LGE)-CMR for evaluation of contrast-enhancement pattern within lesions. Ancillary clinical data were collected in a uniform manner, including baseline cancer-related indices, embolic events, and mortality following CMR

Fig. 2

Representative examples. Representative examples of C_MET classifications, including heterogeneously (left) and diffusely (right) enhancing lesions with intracavitary or intramural location [top: cine-CMR ∣ bottom: LGE-CMR). Lesions denoted by green circles. Note focal hypo-enhancement (yellow arrows) within heterogeneously enhancing lesions, corresponding to C_MET avascular components

Fig. 3

Pulmonary Embolism (PE) in Relation to C_MET Location and Tissue Properties. Top: Clinically documented PE (within 6 months of CMR) among patients grouped based on presence and location of C_MET. Note higher rate of PE among patients with C_MET involving the right ventricle, with differences most marked in analysis limited to intra-cavitary lesions (p < 0.001). Bottom: Location-based comparisons of PE rates among patients with heterogeneous and diffusely enhancing C_MET. Note equivalent rates of PE between patients grouped based on C_MET contrast enhancement pattern

Fig. 4

Mortality status. a Kaplan Meier survival curves for patients with C_MET (solid line) and cancer-matched controls (dotted line), demonstrating increased mortality among patients with C_MET compared to (C_MET -) controls matched for primary cancer type and stage (p = 0.004). b Kaplan–Meier curves among sub-groups with heterogeneously (left) and diffusely enhancing (right) C_MET as compared to respective cancer-matched controls. Note that prognosis varied based on C_MET tissue properties, as evidenced by equivalent mortality risk between diffusely enhancing C_MET and controls (p = 0.21) but increased mortality for patients with heterogeneously enhancing lesions (p = 0.004)