Gout treatment may aid patients with congenital heart disease
Cardiologist says pilot study shows promise, but a larger trial is needed


Date:
August 27, 2020
Source:
University of Cincinnati
Summary:
A drug used to treat gout, probenecid, may improve heart function
in individuals with a particular heart defect, according to
results from a small pilot study. Individuals with congenital
univentricular circulation ran better and their heart performed
better while taking probenecid. The change was small partially
because of the small number of study participants.



FULL STORY ==========================================================================
A drug used to treat gout, probenecid, may improve heart function in individuals with a particular heart defect, according to results from
a small pilot study run by a University of Cincinnati researcher.


==========================================================================
Jack Rubinstein, MD, associate professor in the UC College of Medicine
and UC Health cardiologist, conducted a randomized double-blind
trial which included eight participants who had palliative surgery to
correct a condition of the heart known as congenital univentricular circulation. Each participant received probenecid or a placebo during
a 12-week period.

As part of the study, Rubinstein and co-investigators at Cincinnati
Children's Hospital recruited patients to receive either probenecid
or a placebo for four weeks followed by a four-week period without
medication. They were then required to undergo another four weeks of
alternate treatment. All patients were assessed at baseline immediately preceding the initial use of probenecid or the placebo. This included
symptom reporting, heart imaging and exercise testing to determine
aerobic capacity and endurance.

The study findings are available online in the scholarly journal Pediatric Cardiology.

"Heart function in participants along with their symptoms improved as
a result of the pilot study," says Rubinstein. "Heart contractility was
better. It wasn't a huge increase but enough for us to be able to detect
it. They ran better and their heart pumped better. We observed a small
change, partially because there were a small number of people involved."
"We can repurpose this medicine, long used to treat gout, to improve
how the heart works for kids with univentricular circulation without
any adverse effects," says Rubinstein. "The next step is a larger study
to prove we can make it work safely in the long term." Probenecid has
been shown in recent years to positively influence cardiac function
via effects on the Transient Receptor Potential Vanilloid 2 (TRPV2)
channel in cardiomyocytes, explains Rubinstein. Researchers observed an improvement in cardiac function and exercise performance with probenecid
in patients with a functionally univentricular circulation.

This study also reported work with colleagues at the University of
Colorado that showed that patients with single ventricle physiology
had higher levels of TRPV2 in their hearts, while collaborators at Oslo University Hospital reported a novel mechanism through which probenecid
may particularly be helpful in this patient population.

Univentricular heart (UVH) is a severe congenital cardiac malformation characterized by one functional chamber. The clinical manifestations
include congestive heart failure, failure to thrive, cyanosis, hypoxemia
and neurodevelopmental disabilities.

This study was funded by American Heart Association Award #17GRNT33400014
(Co- funded by The Children's Heart Foundation, J.R, J.G.W, and G.V).


========================================================================== Story Source: Materials provided by University_of_Cincinnati. Original
written by Cedric Ricks. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jack Rubinstein, Jessica G. Woo, Anastacia M. Garcia, Tarek
Alsaied, Jia
Li, Per Kristian Lunde, Ryan A. Moore, Martin Laasmaa, Amanda
Sammons, Wayne A. Mays, Shelley D. Miyamoto, William E. Louch,
Gruschen R.

Veldtman. Probenecid Improves Cardiac Function in Subjects
with a Fontan Circulation and Augments Cardiomyocyte
Calcium Homeostasis. Pediatric Cardiology, 2020; DOI:
10.1007/s00246-020-02427-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200827122117.htm

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