Vascular-variant cardiac amyloid: Cardiac MRI and histopathological appearances

Abstract

Cardiac amyloidosis is an infiltrative cardiomyopathy caused by the deposition of abnormally folded proteins within the myocardium. Several amyloid subtypes have been documented, with diagnosis supported by abnormal serum plasma electrophoresis, multimodality imaging, and endomyocardial biopsy. Herein, we describe the atypical MRI findings of vascular-variant cardiac amyloid supported by histopathological diagnosis. Knowledge of the vascular-variant cardiac amyloid, in which amyloid deposits in the myocardial vasculature rather than the interstitium, will enable clinicians to proceed down appropriate diagnostic and treatment pathways.

Main article

A 63-year-old man presented to our institution with progressive breathlessness on exertion and angina. He was previously fit and healthy with no chronic medical conditions, having competed in multiple marathons per year. He was a non-smoker and had no history of illicit drug use. He took no regular medications. There was no family history of cardiovascular disease. Chest CT demonstrated multiple lytic bone lesions, and serum testing showed raised free kappa light chains (259 mg/L, reference range 3.3–19.4 mg/L) confirming a kappa light chain myeloma diagnosis. Other blood results demonstrated a high sensitivity troponin level of 58 ng/L (reference range 5–14 ng/L), NT-proBNP was 3499 pg/mL (normal range < 250 pg/mL), and C reactive protein was 1.9 mg/L (normal range 0–5 mg/L). Treatment was commenced and complicated by acute decompensated heart failure and recurrent periods of asystole. A dual-lead pacemaker was inserted. Cardiac magnetic resonance imaging was used to assess for cardiac amyloid.

ECG-gated CMR (1.5 T system, Siemens) demonstrated asymmetric hypertrophy of the LV involving the basal and mid-infero-septal segments (Figure 1(a)). The post-contrast myocardial enhancement pattern suggested hypertrophic obstructive cardiomyopathy (HCM)-related fibrosis or a prior episode of myocarditis (Figure 1(b)). There was no contrast enhancement pattern to suggest cardiac amyloid. A subsequent admission with decompensated heart failure prompted an endomyocardial biopsy. Histology revealed thickened, hyalinized blood vessels (Figure 2(a)), and the presence of amyloid was demonstrated by the staining of amorphous material with Congo red (Figure 2(b)) with apple-green birefringence under high-intensity cross-polarized light. Kappa light chain immunohistochemistry was performed and kappa light chains were expressed (Figure 2(c)) in these vessels; lambda light chains were negative (Figure 2(d)). This was consistent with the AL vascular subtype of amyloid, further supported by the increased free kappa light chains in the patient’s serum.

Figure 1.

(a) Short axis cine view demonstrating a thickened LV wall (white arrow) and thickened RV wall (white arrowhead). (b) LGE short axis view showing an atypical enhancement pattern along the LV. Abbreviations: LV = left ventricle, RV = right ventricle, LGE = late gadolinium enhancement.

Figure 2.

On histology, there was thickened hyalinized vessels (Figure 2(a)) and the presence of amyloid was demonstrated by the staining of amorphous material with Congo red (Figure 2(b)) with apple-green birefringence under high-intensity cross-polarized light. Kappa lambda light chain immunohistochemistry was performed, and kappa light chains were expressed (Figure 2(c)) in these vessels; lambda light chains were negative (Figure 2(d)). This was consistent with AL vascular subtype of amyloid, further supported by increased free kappa light chains in the patient’s serum.

Cardiac amyloidosis (CA) is an uncommon cause of cardiomyopathy characterized by deposition in the heart of insoluble fibrils made of low-molecular-weight protein subunits, with two main types being immunoglobulin light chain (AL) and transthyretin (ATTR). ¹ The incidence of the AL subtype is approximately 9–14 cases per million person years. ² The incidence of the rarer vascular variant of AL amyloidosis is difficult to quantify and limited to case series.

CMR is increasingly used to investigate patients with suspected amyloidosis. Global sub-endocardial enhancement, transmural LGE, elevated ECV values, and post-contrast T1 mapping, while not specific for cardiac amyloid, are useful adjuncts in securing a diagnosis. ³

Transmural patterns of late gadolinium enhancement (LGE) distinguish ATTR from AL cardiac amyloidosis. Precise diagnosis of cardiac amyloidosis is crucial given the role of chemotherapy in AL type and with novel therapies for ATTR type currently in development. ⁴

Amyloid deposition typically occurs within the myocardial interstitium; however, a subgroup exhibit predominantly vascular deposition with minimal myocardial interstitial involvement.

A study by Kwon et al. showed that histopathologic involvement of the myocardial vasculature was strongly associated with AL amyloidosis after controlling for age, sex, and indexed LV mass. ⁵

While LVH in transthyretin amyloidosis is associated with interstitial amyloid deposition, the LVH in vascular amyloid is more likely related to amyloid-induced myocyte toxicity. The linear late gadolinium enhancement (LGE) pattern presented here may indicate aggregated vascular amyloid infiltration along the septal perforators superiorly and the posterior descending arterial branches inferiorly, providing a cohesive explanation for the observed LGE pattern. Such findings should raise the possibility of vascular amyloidosis when linear patterns of LGE along vascular pathways alongside LVH are identified in the context of relevant clinical and biochemical factors.

In conclusion, vascular-variant cardiac amyloid (CA) is a rare form of amyloidosis that primarily affects the myocardial vasculature. Multimodality imaging plays a key role in accurately diagnosing CA. While typical imaging features, coupled with endomyocardial biopsy, confirm a diagnosis, atypical imaging findings do not outrule variants of cardiac amyloid. Our case demonstrates an important subtype of CA that was not immediately apparent on imaging. The case highlights the importance of thorough clinical and radiological investigation in arriving at the correct diagnosis.