Could the Presence of Microvascular Retinal Dysfunction Be a New Lens for Suspecting Cardiac Amyloidosis?

Clinical symptoms, pathologic evidence, and functional imaging studies all suggest significant vasculature involvement in amyloidosis; however, data of vascular function in amyloidosis are scarce, and the level of involvement has been poorly defined. Researchers aimed to investigate retinal vascular function in patients with cardiac amyloidosis using a new, validated method for assessing microvascular function—dynamic retinal vessel analysis (DVA)—in combination with comprehensive vascular and laboratory testing.

Patients diagnosed within the Zurich Amyloidosis Network with either cardiac light-chain amyloidosis (AL) or transthyretin-mediated cardiac amyloidosis (ATTR-CM) were recruited for this cross-sectional, prospective, exploratory, observational study between 2016 and 2019 and compared with healthy controls without cardiovascular risk factors (dyslipidemia, hypertension, coronary artery disease, active smoking, and diabetes). The primary end point of flicker‐induced arterial dilation (FIDa) was measured using DVA; other vascular assessments included flow-mediated dilation (FMD) and pulse-wave analysis and velocity (PWA/PWV). Fasting blood samples were obtained at study visit and analyzed for high-sensitivity troponin T (hs-TnT) and N-terminal pro-B–type natriuretic peptide (NT-proBNP) on the same day using standard methods. Estimated glomerular filtration rate (eGFR) was calculated for each patient, with undetectable values replaced by half the lower limit of detection.

A total of 33 patients with cardiac amyloidosis (14 with AL, 19 with ATTR-CM) were matched with 70 healthy controls for a sufficient balance of age, blood pressure, body mass index, glucose, and low-density lipoprotein cholesterol. FIDa was impaired in patients with cardiac amyloidosis compared with healthy controls (P <.001). Similarly, PWV was increased in patients with cardiac amyloidosis compared with healthy controls (P = .018). Other DVA-derived vascular parameters did not significantly differ between patients with cardiac amyloidosis and healthy controls. A comparison of patients with cardiac AL with those with ATTR-CM revealed similar FIDa and other DVA-derived vascular parameters between the 2 subgroups. When comparing retinal vascular function parameters with cardiac and renal biomarkers, significant associations were discovered: FIDa negatively correlated with hs-TnT (P <.001) and NT-proBNP (P <.001), and positively correlated with eGFR (P <.001).

This study revealed impaired retinal FIDa in patients with cardiac amyloidosis compared with healthy controls, with patients with AL and ATTR-CM similarly affected, adding further evidence of vascular dysfunction in cardiac amyloidosis using DVA. The association of retinal microvascular dysfunction with cardiac and renal biomarkers for cardiac amyloidosis may reflect the extent of amyloid deposition and potentially prognosis.

Future studies should be conducted to compare the extent of microvascular dysfunction in patients with amyloidosis with and without cardiac involvement to confidently define the correlation between microvascular dysfunction and amyloidosis. In addition, prospective longitudinal data are needed to establish the utility of DVA in assessing prognosis, risk stratification, and the impact of treatment in cardiac amyloidosis.


Zampiccoli E, Barthelmes J, Kreysing L, et al. Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis. ESC Heart Fail. 2022;9(2):1186-1194.

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