Study identifies underlying dysfunction of seemingly non-critical heart condition

Sep 14, 2010

Repairing small, seemingly benign holes in a child's heart may be more clinically important than previously thought, as dysfunction could be lurking out of sight. These are the findings from a study conducted by doctors and researchers at Nationwide Children's Hospital and the Ohio State University Medical Center examining a subset of the most common form of congenital heart disease, ventricular septal defect. The recently published study appears in the Journal of Molecular and Cellular Cardiology, the official journal of the International Society for Heart Research.

Ventricular septal defect is a defined by one or more holes in the wall that separates the right and left ventricles of the heart. These defects can be large (nonrestrictive) or small (restrictive) and vary in severity depending on size. Medical management of large ventricular septal defects is straightforward in that the hole must be closed or the patient will develop severe, life-threatening complications including and right ventricle failure.

Management of a restrictive ventricular septal defect (rVSD) is less clear.

"rVSD patients typically have normal blood circulation despite an obvious defect and hole in the ventricular wall," said Loren Wold, PhD, FAHA, principal investigator in the Center for Cardiovascular and Pulmonary Research at The Research Institute at Nationwide Children's Hospital and one of the study authors. "Clinically, these patients are usually observed with the hope that the defect will close over time without the need for surgical repair and without the development of or sudden death."

Because rVSD is often considered to be hemodynamically benign, meaning that blood flow appears normal, it is assumed that whole is a reflection of conditions at the cellular and molecular levels. Therefore, few studies have investigated whether changes in the heart at the molecular and cellular levels precede future dysfunction in these patients.

"Without clearly defined evidence supporting optimal care, clinicians are unable to predict which rVSD patients have an increased risk of a poor outcome," said Mark Gerhardt, MD, PhD, associate professor of Anesthesiology at the Ohio State University Medical Center and one of the study authors.

Using an animal model of rVSD, the team at Nationwide Children's Hospital and Ohio State University Medical Center discovered that although blood flow was normal in the models' heart, there were molecular changes, evidence of right ventricular diastolic dysfunction, and impairment of muscle contraction and relaxation at the cellular level.

"These data indicate that despite no overt dysfunction at the level of the whole heart, molecular remodeling and progressive diastolic dysfunction is nevertheless taking place," said Dr. Wold, also a faculty member at The Ohio State University College of Medicine.

"Right ventricular diastolic dysfunction in rVSD is a major finding of this study," said Dr. Gerhardt. "Because the right ventricle is a low-pressure system, small changes in right ventricular compliance may have significant clinical consequences. Our findings indicate that patients with rVSD should be carefully evaluated for right ventricular diastolic dysfunction."

The study also revealed upregulation of the cytoskeletal protein, desmin, in the wall of the right ventricle that precedes functional alterations.

"Desmin may represent a key early marker for future right ventricular dysfunction," said Dr. Wold. "Future research is warranted to determine if increased desmin is the cause or a reaction to diastolic dysfunction."

Findings from the study may lead to a fundamental change in the clinical management of rVSD by providing evidence for early repair of the defect.

Explore further: Diet affects men's and women's gut microbes differently

add to favorites email to friend print save as pdf

Related Stories

Nuclear stress test can detect more than blockages

Jul 14, 2008

A less invasive test commonly used to diagnose coronary disease also may be used to detect one of the leading causes of heart failure, say researchers at the Medical College of Georgia.

Spinal muscular atrophy may also affect the heart

Aug 11, 2010

Along with skeletal muscles, it may be important to monitor heart function in patients with spinal muscular atrophy (SMA). These are the findings from a study conducted by Nationwide Children's Hospital and published online ...

New Clinical Trial Studies Heart Failure Therapy

May 13, 2010

(PhysOrg.com) -- A new clinical trial at UC Health University Hospital is looking at how cardiac resynchronization therapy (CRT) may help individuals with advanced heart failure who may not have been previously ...

Recommended for you

Diet affects men's and women's gut microbes differently

10 hours ago

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published ...

Researchers explore what happens when heart cells fail

11 hours ago

Through a grant from the United States-Israel Binational Science Foundation, Biomedical Engineering Associate Professor Naomi Chesler will embark upon a new collaborative research project to better understand ...

Stem cells from nerves form teeth

14 hours ago

Researchers at Karolinska Institutet in Sweden have discovered that stem cells inside the soft tissues of the tooth come from an unexpected source, namely nerves. These findings are now being published in the journal Nature and co ...

User comments : 0