Novel Clinical Utility of Retinal Imaging in Patients With Heart Failure

Study Overview
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Brief Summary
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Endothelial dysfunction and microvascular disease have been shown to play an important role in both the development and progression of heart failure. Retinal imaging provides a unique opportunity to non-invasively assess retinal microcirculation. Leveraging the non-invasiveness and relative ease of use of retinal imaging, we propose to investigate its clinical utility in assessing endothelial/microvascular dysfunction across the spectrum of heart failure. We aim to test the hypothesis that the degree of abnormality in retinal vessels is associated with heart failure disease severity, endothelial/microvascular dysfunction, and, potentially, treatment responses.

Detailed Description
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This is a human study to test the hypothesis that the degree of abnormality in retinal vessels is associated with heart failure disease severity, endothelial/microvascular dysfunction, and, potentially, treatment responses. Previous epidemiology studies have shown an association between ophthalmic measurements like retinal vessel caliber, retinal microvascular signs, and retinopathy diagnosed from conventional digitized retinal imaging, and the risk of heart failure, as well as alterations in left ventricular structure and function, and even altered filling pressure. Automatic detection software for retinal vessel caliber measurement is widely available, and deep learning algorithms have already enabled reliable detection of retinopathy from captured retinal images. Optical Coherence Tomography (OCT) is an imaging technology that allows for noninvasive, non-contact, high-resolution, cross-sectional imaging of tissue in real time (1). OCT angiography is a new development in OCT imaging that provides visualization of microvascular flow in the retinae of human eyes without the need for intravenous injection of a contrast dye. Several OCT angiography (OCTA) methods allow for three-dimensional noninvasive microvascular visualization. The Zeiss® VisuScout 100, used in the pilot phase of the study, is a handheld retinal camera, commercially available and is already in clinical use at the Cleveland Clinic by Cole Eye Institute specialists for bedside consultations. However, the use of retinal imaging in risk stratifying cardiovascular diseases is unknown, in large part because routine capturing of these images at the point of care is not performed. Novel applications of this non-invasive screening strategy beyond routine ophthalmology-based evaluation may pave the way to scalable population health screening or disease monitoring initiatives. We have established laboratory procedures and equipment for all proposed biomarker evaluations and have published work supporting their mechanistic link to pathophysiologic processes.

Official Title
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Novel Clinical Utility of Retinal Imaging in Patients With Heart Failure: A Pilot Study

Conditions
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Heart Failure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or above; have been diagnosed with HF of any etiology or healthy control; able to provide informed consent and comply with study protocol; able to undergo retinal evaluation using a handheld, automated, non-mydriatric retinal camera; and able to provide written informed consent. Exclusion Criteria: pregnancy or planned pregnancy; photosensitive epilepsy; significant ophthalmologic conditions such as cataract, glaucoma, blindness, or progressive diabetic retinopathy; having undergone retinal laser photocoagulation; any condition which, in the judgment of the investigator, would place a patient at undue risk by being enrolled in the trial, or cause inability to comply with the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Heart Failure out-patients<br>Subjects with heart failure of any etiology | |
| Heart Failure in-patients<br>Subjects with heart failure of any etiology | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinal measurements and heart failure severity | To generate the methodologies and establish workflow, and to generate preliminary data to demonstrate the association of retinal measurements with heart failure disease severity. | 4 years | 
| Retinal measurements and exercise capacity | To generate the methodologies and establish workflow, and to generate preliminary data to demonstrate the association of retinal measurements with exercise capacity represented by 6 Minute Walk Test distance | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood analysis | Blood samples may be collected to assess for asymmetric dimethylarginine levels (ADMA, a surrogate of endothelial dysfunction) | 4 years | 
| Urine analysis | Urine samples may be collected to obtain urine albumin/creatinine ratio (UACR) for microalbuminuria (a surrogate of microvascular disease) | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure