Personalized Virtual Hearts Could Improve Cardiac Surgery

Digital replicas of patients' hearts can identify hidden, irregular heart tissue for surgeons to destroy

3 min read
Researchers simulate irregular heartbeats to find exactly where they emerge from
This simulation of the upper chambers of a heart shows ablation targets specific to this patient.
Image: Patrick M. Boyle and Natalia A. Trayanova

Natalia Trayanova has spent years creating computer models that simulate individual patients’ hearts. Now, the Johns Hopkins University engineer is putting those simulations into the hands of surgeons.

In research published this week in the journal Nature Biomedical Engineering, Trayanova’s team created personalized heart simulations to guide the surgeries of 10 patients with persistent irregular heartbeats. The virtual hearts predicted where surgeons should destroy heart tissue that could produce erratic electrical signals now and in the future.

The proof-of-concept study sets the stage for an FDA-approved clinical trial of 160 patients slated to begin this fall. That trial will assess whether the virtual heart-guided surgery is more accurate and effective than today’s conventional, one-size-fits-all procedure.

Last year, surgeons used the Johns Hopkins team’s 3D virtual simulation of the heart’s ventricles—the two large, lower chambers—to guide the surgery of five patients with faster-than-normal heartbeats. Trayanova’s team has also used the technology to identify patients at high risk of cardiac arrest.

The current study focuses on abnormal electrical signals in the atria—the two upper chambers of the heart—which cause persistent irregular heartbeats, a common condition known as atrial fibrillation (AF). AF is the most common cause of irregular heartbeats, expected to affect as many as 10 million Americans by 2020. “It’s a huge health care burden,” says Trayanova, director of the Computational Cardiology Laboratory at Hopkins.

Patients can experience either intermittent or persistent AF. In either case, doctors traditionally enter the heart with a catheter and burn away the tissue around the atria’s four pulmonary veins, a region implicated in the electrical misfiring. The procedure works well for patients with intermittent AF, says Trayanova, but not so well for those with persistent AF, particularly when patients have scarring in the tissue, which is age related. These patients commonly return to the operating room for repeat surgeries, even up to four or five times, each time creating more scar tissue in the heart, which can lead to more misfiring.

The new individualized procedure, called Optimal Target Identification via Modeling of Arrhythmogenesis (OPTIMA), could target all the problem areas of the heart in the first surgical attempt, including those that will cause electrical misfiring in the future.

Here’s how it works: First, a patient with AF undergoes contrast-enhanced MRI heart scans, which document any scarring on the heart. Next, the engineers segment the images into a geometric representation of the atria. In a computer program, they populate that representation with virtual heart cells. Cells behave differently around normal or scarred heart tissue, so the digital heart gradually takes on the same behaviors of the patient’s heart.

Researchers simulate irregular heartbeats to find exactly where they emerge from Researchers use a digital map of a patient’s heart to perform several rounds of virtual ablation and figure out how to avoid scarring that could disrupt electrical signals. Gif: Patrick M. Boyle and Natalia A. Trayanova

Next, the engineers prod the virtual heart with small electrical stimuli to see how it will react. “We don’t know a priori, by looking at the image, what’s going to happen,” says Trayanova. So, they watch, and mark down areas where a stimulus prompts an irregular heartbeat. Those are the sites surgeons will need to destroy by burning, a procedure called ablation.

But identifying those initial sites is not enough, says Trayanova. After marking down all the initial problem areas, the team performs virtual surgery, destroying those areas and adding new virtual scars, called lesions, to the model. Then, they do the testing all over again, as new scars can lead to the generation of additional misfiring heart tissue.

“We repeat this several times to find the optimal set of lesions so that when you execute them, the patient never returns to the hospital,” says Trayanova. Typically, by the third round, there are no more hidden areas that can cause abnormal electrical signals.

Finally, an electronic map of the patient’s heart is sent to the system that operating physicians use during surgery, displayed on screens in the operating room. The surgeon uses this map to guide the catheter to the tissues that need to be destroyed.

Normally, an estimated 50 percent of persistent AF patients return to the hospital for additional surgeries. Of the 10 patients who underwent the personalized OPTIMA procedure, only one came back for an additional treatment.

The personalized approach is likely to be more expensive than a typical AF surgery because it involves MRI scanning. However, preventing a patient from returning to the hospital for additional procedures can result in an overall cost savings, says Trayanova. She has submitted a patent application for the technology. “We want a treatment that works, so someone doesn’t have to come in to be ablated five times,” she says. 

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This CAD Program Can Design New Organisms

Genetic engineers have a powerful new tool to write and edit DNA code

11 min read
A photo showing machinery in a lab

Foundries such as the Edinburgh Genome Foundry assemble fragments of synthetic DNA and send them to labs for testing in cells.

Edinburgh Genome Foundry, University of Edinburgh

In the next decade, medical science may finally advance cures for some of the most complex diseases that plague humanity. Many diseases are caused by mutations in the human genome, which can either be inherited from our parents (such as in cystic fibrosis), or acquired during life, such as most types of cancer. For some of these conditions, medical researchers have identified the exact mutations that lead to disease; but in many more, they're still seeking answers. And without understanding the cause of a problem, it's pretty tough to find a cure.

We believe that a key enabling technology in this quest is a computer-aided design (CAD) program for genome editing, which our organization is launching this week at the Genome Project-write (GP-write) conference.

With this CAD program, medical researchers will be able to quickly design hundreds of different genomes with any combination of mutations and send the genetic code to a company that manufactures strings of DNA. Those fragments of synthesized DNA can then be sent to a foundry for assembly, and finally to a lab where the designed genomes can be tested in cells. Based on how the cells grow, researchers can use the CAD program to iterate with a new batch of redesigned genomes, sharing data for collaborative efforts. Enabling fast redesign of thousands of variants can only be achieved through automation; at that scale, researchers just might identify the combinations of mutations that are causing genetic diseases. This is the first critical R&D step toward finding cures.

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