Prognostic utility of differential tissue characterization of cardiac neoplasm and thrombus via late gadolinium enhancement cardiovascular magnetic resonance among patients with advanced systemic cancer

Abstract

Background: Late gadolinium enhancement (LGE-) cardiovascular magnetic resonance (CMR) is well-validated for cardiac mass (C_MASS) tissue characterization to differentiate neoplasm (C_NEO) from thrombus (C_THR): Prognostic implications of C_MASS subtypes among systemic cancer patients are unknown.

Methods: C_MASS + patients and controls (C_MASS -) matched for cancer diagnosis and stage underwent a standardized CMR protocol, including LGE-CMR (IR-GRE) for tissue characterization and balanced steady state free precession cine-CMR (SSFP) for cardiac structure/function. C_MASS subtypes (C_NEO, C_THR) were respectively defined by presence or absence of enhancement on LGE-CMR; lesions were quantified for tissue properties (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR) and size. Clinical follow-up was performed to evaluate prognosis in relation to C_MASS etiology.

Results: The study population comprised 126 patients with systemic neoplasms referred for CMR, of whom 50% (n = 63) had C_MASS + (C_NEO = 32%, C_THR = 18%). Cancer etiology differed between C_NEO (sarcoma = 20%, lung = 18%) and C_THR (lymphoma = 30%, GI = 26%); cardiac function (left ventricular ejection fraction: 63 ± 9 vs. 62 ± 10%; p = 0.51∣ right ventricular ejection fraction: 53 ± 9 vs. 54 ± 8%; p = 0.47) and geometric indices were similar (all p = NS). LGE-CMR tissue properties assessed by CNR (13.1 ± 13.0 vs. 1.6 ± 1.0; p < 0.001) and SNR (29.7 ± 20.4 vs. 15.0 ± 11.4, p = 0.003) were higher for C_NEO, consistent with visually-assigned diagnostic categories. C_THR were more likely to localize to the right atrium (78% vs. 25%, p < 0.001); nearly all (17/18) were associated with central catheters. Lesion size (17.3 ± 23.8 vs. 2.0 ± 1.5 cm²; p < 0.001) was greater with C_NEO vs. C_THR, as was systemic disease burden (cancer-involved organs: 3.6 ± 2.0 vs. 2.3 ± 2.1; p = 0.02). Mortality during a median follow-up of 2.5 years was markedly higher among patients with C_NEO compared to those with C_THR (HR = 3.13 [CI 1.54-6.39], p = 0.002); prognosis was similar when patients were stratified by lesion size assessed via area (HR = 0.99 per cm² [CI 0.98-1.01], p = 0.40) or maximal diameter (HR = 0.98 per cm [CI 0.91-1.06], p = 0.61). C_THR conferred similar mortality risk compared to cancer-matched controls without cardiac involvement (p = 0.64) whereas mortality associated with C_NEO was slightly higher albeit non-significant (p = 0.12).

Conclusions: Among a broad cancer cohort with cardiac masses, C_NEO defined by LGE-CMR tissue characterization conferred markedly poorer prognosis than C_THR, whereas anatomic assessment via cine-CMR did not stratify mortality risk. Both C_NEO and C_THR are associated with similar prognosis compared to C_MASS - controls matched for cancer type and disease extent.

Keywords: Cardiac mass; Cardiac metastases; Cardiac thrombus; Cardio-oncology.

Fig. 1

Study Design. Schematic of overall study design, inclusive of baseline LGE-CMR (for mass tissue characterization) and subsequent clinical follow-up (for all cause mortality). Note that for all C_MASS + patients, etiology (C_NEO vs. C_THR) was established based on presence or absence of enhancement on LGE-CMR

Fig. 2

C_MASS Enhancement Patterns Identified by LGE-CMR. a C_NEO: Representative examples of diffuse (left) and heterogeneous (right) enhancement as manifest on (long TI) LGE-CMR (lesions denoted within green circles). Corresponding cine-CMR images shown on bottom for purpose of anatomic localization. Both lesions (diffusely enhancing pericardial lesion adjacent to distal left ventricle (LV), heterogeneously enhancing right atrial (RA) lesion) identified in patients with advanced (stage IV) melanoma. b C_THR: Typical non-enhancing lesion deemed consistent with avascular composition (thrombus). Note that RA localization of lesion, which was identified by LGE-CMR following placement of central catheter for therapeutic management of stage IV ovarian cancer

Fig. 3

Quantitative Tissue Properties of Cardiac Neoplasm and Thrombus. a SNR (left) and CNR (right) compared between C_NEO and C_THR (data shown as overall distribution [line bars] together with 25–75% distribution [box], and median [central line]). Note that SNR and CNR were generally higher for C_NEO, consistent with contrast-enhancement secondary to vascular supply. b SNR and CNR comparisons inclusive of C_NEO subtypes (diffuse and heterogeneous enhancement). Increased CNR within heterogeneously enhancing lesions (p < 0.001 vs. other types) consistent with interspersed regions with and without adequate vascular supply

Fig. 4

Receiver Operating Characteristics Curves. ROC curves for CNR, SNR, and lesion size (length, area) as indices for discriminating between C_MASS types. As shown, CNR yielded highest overall diagnostic performance (based on area under the curve [AUC]) for differentiating between C_NEO and C_THR. AUC associated p-values reflect comparisons to null hypothesis (area = 0.5)

Fig. 5

Mortality Status. Kaplan Meier survival curves for patient groups partitioned based on C_MASS status (solid blue = C_NEO, dotted blue = C_NEO control; solid red = C_THR, dotted line = C_THR control): For both C_NEO and C_THR, controls were matched for primary cancer type and stage. Note higher mortality among patients with C_NEO vs. C_THR (p = 0.002); C_THR conferred similar mortality risk compared to respective cancer-matched controls whereas mortality associated with C_NEO was slightly higher albeit non-significant