Medical Design and Outsourcing

  • Home
  • Medical Device Business
    • Mergers & Acquisitions
    • Financial
    • Regulatory
  • Applications
    • Cardiovascular
    • Devices
    • Imaging
    • Implantables
    • Medical Equipment
    • Orthopedic
    • Surgical
  • Technologies
    • Contract Manufacturing
    • Components
    • Electronics
    • Extrusions
    • Materials
    • Motion Control
    • Prototyping
    • Pumps
    • Tubing
  • Med Tech Resources
    • DeviceTalks Tuesdays
    • Digital Editions
    • eBooks
    • Manufacturer Search
    • Medical Device Handbook
    • MedTech 100 Index
    • Podcasts
    • Print Subscription
    • The Big 100
    • Webinars / Digital Events
    • Whitepapers
    • Video
  • 2022 Leadership in MedTech
    • 2022 Leadership Voting!
    • 2021 Winners
    • 2020 Winners
  • Women in Medtech

Heart Defect Prediction Technology Could Lead to Earlier, More Informed Treatment

May 23, 2016 By CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER

An experimental model uses genetics-guided biomechanics and patient-derived stem cells to predict what type of inherited heart defect a child will develop, according to authors of a new study in the journal Cell.

A multi-institutional team developing the technology – and led by the Cincinnati Children’s Heart Institute – reports May 19 it would let doctors intervene earlier to help patients manage their conditions and help inform future pharmacologic treatment options. In laboratory tests, the model accurately predicts whether mouse models and stem-cell derived heart cells from human patients will develop a hypertrophic or dilated cardiomyopathy.

With cells illuminated by fluoresced antibodies, this microscopic photograph of sarcomeres – the part of heart muscle that generates tension and contraction – shows a mutant troponin protein used to study inherited cardiomyopathy. Researchers at Cincinnati Children’s Hospital Medical Center and the Howard Hughes Medical Institute have developed a computational algorithm that allows them to measure biochemical and physical changes and predict if heart tissues will develop a hypertrophic cardiomyopathy or dilated cardiomyopathy. Researchers report May 19 in the journal Cell the technology could one day allow physicians to intervene earlier to help patients with mutations that cause inherited cardiomyopathies. (Credit: Cincinnati Children’s)

“This technology would make it possible to predict the eventual cardiac phenotype in pediatric patients and help guide their treatment and future monitoring,” said Jeffery Molkentin, PhD, lead author and a researcher in the Division of Molecular Cardiovascular Biology at Cincinnati Children’s and the Howard Hughes Medical Institute. “It could help when counseling patients about athletic endeavors, in which sudden death can occur with hypertrophic cardiomyopathy. Or it could help decide whether certain patients should consider an implantable cardioverter defibrillator to prevent sudden death as they grow into young adulthood.”

Inherited cardiomyopathy is a genetically diverse group of heart muscle diseases affecting about one of every 500 people. There are two primary clinical manifestations: hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The diseases involve nearly 1,500 different gene mutations in sarcomeres, the part of the heart muscle that generates tension and contraction.

In HCM, the heart’s chambers and valves grow so that they are not symmetric. The dimension of the ventricular chamber is reduced, the interventricular septum thickens, and patients suffer from diastolic dysfunction (in which heart muscle doesn’t relax normally), causing an increased risk of sudden death from arrhythmia. With DCM, people have an enlarged left ventricular chamber accompanied by a lengthening of heart cells (myocytes) that results in reduced systolic function and eventually heart failure.

Effective drug regimens to manage the conditions do not exist, although there is research looking for new drugs. The only effective treatment at present is a heart transplant. This leaves an urgent need to develop new technologies to manage, treat, cure or prevent the diseases, according to researchers. 
In developing the technology, scientists analyzed how sarcomeres generate tension coupled with alterations in calcium cycling, which is critical to heart function. The coupling of tension generation and calcium cycling is altered in patients with sarcomeric gene mutations. The alteration can be measured and then used to predict how the heart will change as disease progresses, Molkentin said.

To study the influence of gene mutations on this process, researchers tested an array of genetically altered mice. The mouse models were either normal (wild type) mice or those expressing different gene mutations for various cardiomyopathies.

This allowed researchers to examine tension generation and associated calcium cycling rates through heart muscle in a highly defined manner. That information was used to create a mathematical model for disease prediction that integrates the total tension generated by isolated cardiomyocytes. The tension-integrated, algorithm-based model was able to predict if hearts in mouse models would undergo hypertrophic or dilated cardiac growth.

The scientists next tested the computational model on human cells from cardiomyopathy patients by using induced pluripotent stem cell (iPSC) technology. Reprogrammed and derived from actual patient skin fibroblast cells, iPSCs can become virtually any cell type in the human body and then be used for scientific investigation of disease properties.

Molkentin and his colleagues generated patient-specific cardiomyocytes – which under a microscope can actually be seen pulsating rhythmically similar to a beating heart. Patient-derived iPSCs also carry the same genetic makeup (including mutations) as the person donating original starter cells. In the study, iPSC heart cells developed the same cardiomyopathy tension deficits as the patient’s own hearts.

Researchers then used their heart defect prediction method to see how accurately it determined the heart defect type of specific cardiomyopathy patients. With collaborators at the Stanford University School of Medicine, Molkentin and his colleagues generated four lines of developing, early-stage patient-specific iPSC heart cells (cardiomyocytes). They report that their technology accurately determined the HCM vs. DCM heart defect of the donor patients.

Researchers continue to develop and test the technology by using it to determine the cardiac disease state of patients with specific mutations in a sarcomere encoding gene. They caution the technology is years away from potential clinical use, pending further testing and refinement.

Related Articles Read More >

A portrait of Dr. Philip Adamson
Expect more heart and lung failure years after COVID, Abbott’s heart failure CMO says
iRhythm stays silent on federal grand jury subpoenas
iRhythm stock soars on Street-beating Q1
A Medtronic HVAD pump opened up to show the inner workings
Medtronic investigates HVAD pump welds after patient deaths

DeviceTalks Weekly.

May 20, 2022
DeviceTalks Boston Post-Game – Editors’ Top Moments, Insulet’s Eric Benjamin on future of Omnipod 5
See More >

MDO Digital Edition

Digital Edition

Subscribe to Medical Design & Outsourcing. Bookmark, share and interact with the leading medical design engineering magazine today.

MEDTECH 100 INDEX

Medtech 100 logo
Market Summary > Current Price
The MedTech 100 is a financial index calculated using the BIG100 companies covered in Medical Design and Outsourcing.
DeviceTalks

DeviceTalks is a conversation among medical technology leaders. It's events, podcasts, webinars and one-on-one exchanges of ideas & insights.

DeviceTalks

New MedTech Resource

Medical Tubing

Enewsletter Subscriptions

Enewsletter Subscriptions

MassDevice

Mass Device

The Medical Device Business Journal. MassDevice is the leading medical device news business journal telling the stories of the devices that save lives.

Visit Website
MDO ad
Medical Design and Outsourcing
  • MassDevice
  • DeviceTalks
  • MedTech 100 Index
  • Medical Tubing + Extrusion
  • Drug Delivery Business News
  • Drug Discovery & Development
  • Pharmaceutical Processing World
  • R&D World
  • About Us/Contact
  • Advertise With Us
  • Subscribe to Print Magazine
  • Subscribe to E-newsletter
  • Attend our Monthly Webinars
  • Listen to our Weekly Podcasts
  • Join our DeviceTalks Tuesdays Discussion

Copyright © 2022 WTWH Media, LLC. All Rights Reserved. Site Map | Privacy Policy | RSS

Search Medical Design & Outsourcing

  • Home
  • Medical Device Business
    • Mergers & Acquisitions
    • Financial
    • Regulatory
  • Applications
    • Cardiovascular
    • Devices
    • Imaging
    • Implantables
    • Medical Equipment
    • Orthopedic
    • Surgical
  • Technologies
    • Contract Manufacturing
    • Components
    • Electronics
    • Extrusions
    • Materials
    • Motion Control
    • Prototyping
    • Pumps
    • Tubing
  • Med Tech Resources
    • DeviceTalks Tuesdays
    • Digital Editions
    • eBooks
    • Manufacturer Search
    • Medical Device Handbook
    • MedTech 100 Index
    • Podcasts
    • Print Subscription
    • The Big 100
    • Webinars / Digital Events
    • Whitepapers
    • Video
  • 2022 Leadership in MedTech
    • 2022 Leadership Voting!
    • 2021 Winners
    • 2020 Winners
  • Women in Medtech