Novel Clinical Utility of Retinal Imaging in Patients With Heart Failure

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05086978
• Other study ID #: 21-940
• Status: Enrolling by invitation
• Start date: February 1, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: October 2023
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 250
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

References & Publications (7)

Chandra A, Seidelmann SB, Claggett BL, Klein BE, Klein R, Shah AM, Solomon SD. The association of retinal vessel calibres with heart failure and long-term alterations in cardiac structure and function: the Atherosclerosis Risk in Communities (ARIC) Study. Eur J Heart Fail. 2019 Oct;21(10):1207-1215. doi: 10.1002/ejhf.1564. Epub 2019 Aug 1. — View Citation

Cheung N, Bluemke DA, Klein R, Sharrett AR, Islam FM, Cotch MF, Klein BE, Criqui MH, Wong TY. Retinal arteriolar narrowing and left ventricular remodeling: the multi-ethnic study of atherosclerosis. J Am Coll Cardiol. 2007 Jul 3;50(1):48-55. doi: 10.1016/j.jacc.2007.03.029. Epub 2007 Jun 18. — View Citation

Chung YR, Park SJ, Moon KY, Choi SA, Lim HS, Park SW, Kim JH, Lee K. Diabetic retinopathy is associated with diastolic dysfunction in type 2 diabetic patients with non-ischemic dilated cardiomyopathy. Cardiovasc Diabetol. 2017 Jul 6;16(1):82. doi: 10.1186/s12933-017-0566-y. — View Citation

Goto I, Katsuki S, Ikui H, Kimoto K, Mimatsu T. Pathological studies on the intracerebral and retinal arteries in cerebrovascular and noncerebrovascular diseases. Stroke. 1975 May-Jun;6(3):263-9. doi: 10.1161/01.str.6.3.263. — View Citation

Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol. 2012 Oct 16;60(16):1455-69. doi: 10.1016/j.jacc.2011.11.082. Epub 2012 Sep 19. — View Citation

Tanaka M, Fujiwara H, Onodera T, Wu DJ, Matsuda M, Hamashima Y, Kawai C. Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy. Circulation. 1987 Jun;75(6):1130-9. doi: 10.1161/01.cir.75.6.1130. — View Citation

Wong TY, Rosamond W, Chang PP, Couper DJ, Sharrett AR, Hubbard LD, Folsom AR, Klein R. Retinopathy and risk of congestive heart failure. JAMA. 2005 Jan 5;293(1):63-9. doi: 10.1001/jama.293.1.63. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Blood analysis	Blood samples may be collected to assess for asymmetric dimethylarginine levels (ADMA, a surrogate of endothelial dysfunction)	4 years
Secondary	Urine analysis	Urine samples may be collected to obtain urine albumin/creatinine ratio (UACR) for microalbuminuria (a surrogate of microvascular disease)	4 years