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Cardiovascular Medicine, Genetics, Research, Stanford News

A cheaper, faster way to find genetic defects in heart patients

A cheaper, faster way to find genetic defects in heart patients

15907993264_87339bc83f_zIn most people, heart disease develops through a lifetime of cigarettes, trans fats or high glycemic foods. For only a minority of patients does the cause lie in their genes. But when such atypical patients show up for treatment, figuring out why their hearts aren’t working has been a huge challenge for their doctors. The process of deciding if a heart patient’s problem is genetic and, if so, which gene defects might be causing the problem can take weeks or months, cost a thousand dollars or more, and, at the end, leave physicians still scratching their heads over a mountain of uncertain data.

A new genetic test being developed by pathologist Kitchener Wilson, MD, PhD and cardiology and radiology professor Joseph Wu, MD, PhD, may be able to accurately pinpoint the likely genetic causes of a heart patient’s elusive condition in just a couple of days.

Wilson and Wu say that for a patient with a heart condition that’s difficult to diagnose, it makes no sense to sequence the entire 22,000-gene human genome. Such whole-genome sequencing is costly, time consuming, and produces data marred by small but important errors.

So, taking a more focused approach, Wilson and Wu’s team designed a streamlined assay, or test, that looks at just the 88 genes known to carry mutations that cause heart problems. Materials for the new assay cost about $100, and results are back within three days.

Their approach — surveying a small subgroup of relevant genes instead of the whole genome — is already used to look for other genetic diseases, such as cystic fibrosis. But cystic fibrosis results from mutations in a single gene. “The heart diseases are more challenging just because there are so many genes to sequence,” says Wilson.

Wilson and Wu’s assay is a variation on “complementary long padlock probes,” or cLPPs, a class of genetic probes developed at the Stanford Genome Technology Center. These simple probes accurately target specific parts of the genome and are easily customized to target genes of interest. Wilson and Wu spearheaded the effort to put cLPPs to work on genes connected with heart problems and reported their work in the journal Circulation Research, with Wu as senior author and Wilson as first author.

If further tests validate the assay, it could shorten the time it takes to diagnose difficult or unusual heart disease cases—like that of basketball player Hank Gathers above — hastening appropriate treatment for atypical cardiac patients.

Previously: At Stanford Cardiovascular Institute’s annual retreat, a glimpse into the future of cardiovascular medicine and Coming soon: A genome test that costs less than a new pair of shoes
Photo by: Liviu Ghemaru

Big data, Cardiovascular Medicine, Chronic Disease, In the News, Research, Stanford News

Using “big data” to improve patient care: Researchers explore a-fib treatments

Using "big data" to improve patient care: Researchers explore a-fib treatments

Turakhia photoA Stanford cardiac electrophysiologist and colleagues have used a unique research method to learn more about atrial fibrillation. Mintu Turakhia, MD, and collaborators at Medtronic and Massachusetts General Hospital, extracted data out of decades of continuously recorded medical information from implanted medical devices – pacemakers and defibrillators — in 10,000 heart patients. Then they linked it to medical records, and analyzed it.

The researchers’ goal was to explore whether patients who experienced sudden attacks of a-fib, an irregular and rapid heart rate caused by spasms of the heart’s upper chambers, should be treated with long-term anticoagulants like those who had permanent a-fib or whether perhaps temporary drug therapy could be considered an option. They wanted to know if a patient’s risk of stroke changes as a-fib comes and goes.

The results, which were published recently in Circulation: Arrhythmia and Electrophysiology, found that patients were at an increased risk of stroke the first seven days after their hearts went into a-fib.

A-fib, which afflicts more than 3 million Americans, is known to increase a patient’s risk of stroke – but exactly when this risk occurs is controversial. Currently, physicians recommend long-term anticoagulation for patients, whether the a-fib occurs in sudden attacks or is continuous. This study indicates that transient use of anticoagulants could be an option for some patients and deserves further investigation. Future treatment plans might explore the idea of some kind of wearable device that shows when a patient goes in and out of a-fib, then taking medications just when needed rather than for a lifetime, said Turakhia.

Turakhia told me the study also provides an important example of how using “big data” research methods can ultimately lead to improved clinical care. In an email, he explained:

This is truly a big data approach where we took raw data from implanted pacemakers and implanted defibrillators and linked it to clinical data. The medical device data comes from home remote monitoring systems that patients have and goes to the cloud. We pulled the raw data off the cloud and linked it to VA (Veterans Affairs) electronic health records, VA claims, Medicare claims, and death records. This is truly a novel approach where we are assembling highly disparate data sources and linking them to gain insight into disease.

Previously: A little help from pharmacists helps a-fib patients adhere to prescriptions, Study highlights increased risk of death among patients with atrial fibrillation who take digoxin and What is big data?
Photo of Turakhia by Norbert von der Groeben

Cardiovascular Medicine, Evolution, Genetics, Research, Science

Ethiopian gene offers potential help for hypoxia

Ethiopian gene offers potential help for hypoxia

8494671414_5bc71743c8_zGene therapies have been developed for color blindness, Parkinson’s, SCID, and muscular dystrophy, among others. Now there soon could be another to add to the list: hypoxia, or oxygen deprivation.

In a study published in PNAS, researchers investigated how mice with lower levels of the endothelin receptor type B (EDNRB) gene – a gene that is present among Ethiopians, who evolved to live at high elevations where oxygen levels are low – fare in hypoxic conditions. It found that even with five percent oxygen, lower than you’d find atop Mount Everest, the mice with the gene alteration survived. They managed to get oxygen to their vital organs with the help of several “downstream” genes that are regulated by EDNRB.

According to a press release, these three heart-specific genes “help heart cells perform crucial functions such as transport calcium and contract. The finding provides a direct molecular link between EDNRB levels and cardiovascular performance.”

The implications of this work are described in the release by senior author Gabriel Haddad, MD, professor and chair of pediatrics at UC San Diego School of Medicine: “In addition to improving the health of the more than 140 million people living above 8,000 feet, information on how Ethiopians have adapted to high altitude life might help us develop new and better therapies for low oxygen-related diseases at sea level — heart attack and stroke, for example.” Haddad and his team are now testing therapeutic drugs that inhibit ENDRB.

Previously: Near approval: A stem cell gene therapy developed by Stanford researcher, Using genetics to answer fundamental questions in biology, medicine, and anthropology and “It’s not just science fiction anymore”: ChildX researchers talk stem cell and gene therapy
Photo by mariusz klozniak

Cardiovascular Medicine, Medical Apps, Public Health, Research, Stanford News

Stanford’s MyHeart Counts app reaches overseas to Hong Kong and the UK

Stanford's MyHeart Counts app reaches overseas to Hong Kong and the UK

MyHeart Counts on phoneIn an effort to continue signing up new participants for their heart research study at groundbreaking speeds, researchers at Stanford launched their iPhone app MyHeart Counts overseas in Hong Kong and the United Kingdom today. The goal is to reach out far and wide — quickly.

To date, about 41,000 users have signed up for the free app launched in March, which allows users to learn about their own heart health while also participating in a large-scale heart study. That’s an unprecedented number of people in such a short amount of time, researchers say, adding that it’s only the beginning. From our press release on today’s launch overseas:

“The idea is to move into one country at a time until we go global,” said Euan Ashley MD, a professor of cardiovascular medicine at Stanford and co-investigator for the MyHeart Counts study. “We hope to add more countries every few months.

“We are ready to take the study as far as it will go. We would like to build a new Framingham heart study for the ages,” Ashley said, referring to the long-term cardiovascular study that has followed three generations of participants in Framingham, Massachusetts. “We would like millions of participants.”

MyHeart Counts is the first of the initial handful of apps designed using ResearchKit, Apple’s open-source software platform for creating medical-research apps, to expand overseas. Along with its reach into Hong Kong and the U.K., the app is also being upgraded today, providing more information to users about their own heart health and breaking heart health news. The press release gives a brief overview of what the app does:

The free app offers users a simple way to participate in the study, complete tasks and answer surveys from their iPhones. Once every three months, participants are asked to monitor one week’s worth of physical activity, complete a 6-minute walk fitness test if they are able, and enter their risk-factor information. The app now also delivers a comprehensive summary of each user’s heart health and areas for improvement.

Previously: Lights, camera action: Stanford cardiologist discusses MyHeart Counts on ABC’s NightlineBuild it (an easy way to join research studies) and the volunteers will comeMyHeart Counts app debuts with a splash and Stanford launches iPhone app to study heart health

Big data, BigDataMed15, Cardiovascular Medicine, Medical Apps, Stanford News, Videos

A look at the MyHeart Counts app and the potential of mobile technologies to improve human health

A look at the MyHeart Counts app and the potential of mobile technologies to improve human health

Keynote talks and presentations from the 2015 Big Data in Biomedicine conference at Stanford are now available on the Stanford YouTube channel. To continue the discussion of how big data can be harnessed to improve the practice of medicine and enhance human health, we’re featuring a selection of the videos on Scope.

At last count, the number of iPhone owners who have downloaded the MyHeart Counts app and consented to participate in a large-scale, human heart study had reached 40,000. The first-of-its-kind mobile app was designed by Stanford Medicine cardiologists as a way for users to learn about their heart health while simultaneously helping advance the field of cardiovascular medicine.

Built on Apple’s ResearchKit framework, the app leverages the iPhone’s built-in motion sensors to collect data on physical activity and other cardiac risk factors for a research study. The MyHeart Counts study also draws on the strength of Stanford Medicine’s Biomedical Data Science Initiative.

At the 2015 Big Data in Biomedicine conference, Euan Ashley, MD, a cardiologist at Stanford and co-investigator for the MyHeart Counts study, shared some preliminary findings with the audience. Check out the full talk to learn more about how the app is helping researchers better understand Americans’ health habits and what states have the happiest, most physically active and well-rested residents.

Previously: On the move: Big Data in Biomedicine goes mobile with discussion on mHealth, MyHeart Counts shows that smartphones are catching on as new research tool, Lights, camera, action: Stanford cardiologist discusses MyHeart Counts on ABC’s Nightline, MyHeart Counts app debuts with a splash and Stanford launches iPhone app to study heart health.

Cardiovascular Medicine, Chronic Disease, In the News, Research, Stanford News, Transplants

Are donor hearts getting wasted?

Are donor hearts getting wasted?

heart choiceI wrote a press release recently on a study that showed a high percentage of donated hearts were not being used, raising concerns that some were getting wasted when they could be used to save lives. This made me curious about the process of just how a donor heart, which ideally has about a two-hour window before it gets transplanted to a patient with heart failure, gets matched.

The result is a Stanford Medicine magazine story titled “Heart Choices” that describes this process, the tough decisions that family members make when a loved one donates a heart, and the excruciating waiting that patients in need of a new heart go through.

Most importantly the article asks the question: Should more “high-risk” donor hearts be used? An estimated 20,000 people across the country are waiting for new hearts, and only a few thousand transplants happen on average per year. My story explains the dilemma:

The general assumption is that there simply are not enough donor hearts available to meet a growing demand. But new research is questioning that assumption. Some researchers and surgeons claim that thousands of donor hearts that could be used are turned away each year. The hearts are considered marginal because they come from older, sicker or riskier donors, but many argue they are safe for transplant, and could be saving lives.

“As patients wait longer, they often get sicker, and we often lose patients,” says Stanford cardiologist Kiran Khush, MD, whose research reports that 65 percent of available heart donations are discarded because of stringent acceptance criteria. Yet the criteria have not been critically evaluated, she says. “Increasing the supply of donor hearts is, of course, a great concern of mine.”

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Cardiovascular Medicine, Chronic Disease, Imaging, Research, Stanford News, Technology

DNA damage seen after CT scanning, study shows

DNA damage seen after CT scanning, study shows

16288548276_e155ec8843_zUsing new laboratory techniques, Stanford scientists have been able to get a closer look at what happens inside the cells of patients undergoing medical imaging techniques. In a study published today, their research clearly shows that there is cellular damage in heart patients after CT scanning.

The researchers explained to me in interviews for a press release on the study that this doesn’t link CT scans to cancer. But as Patricia Nguyen, MD, lead author said in the release, it is further indication for caution:

“Whether or not this (cellular damage) causes cancer or any negative effect to the patient is still not clear, but these results should encourage physicians toward adhering to dose reduction strategies.”

Due to an explosion in the use CT scans for heart patients over the past decade, public health concerns have been raised over whether there might be a causal link with cancer. But until now, little has been known about exactly what happens at a cellular level when patients undergo CT scanning, a type of medical imaging which exposes them to low-dose radiation. This study took advantage of new laboratory techniques that made it possible to look inside cells of patients after they underwent CT scanning. As Nguyen explained in my release:

“Because we don’t know much about the effects of low-dose radiation — all we know is about high doses from atomic bomb blast survivors — we just assume it’s directly proportional to the dose. We wanted to see what really happens at the cellular level.”

Researchers examined the blood of 67 patients undergoing cardiac CT angiography using such techniques as whole-genome sequencing and flow cytometery to measure biomarkers of DNA damage. The results:

… showed an increase in DNA damage and cell death, as well as increased expression of genes involved in cell repair and death, the study said. Although most cells damaged by the scan were repaired, a small percentage of the cells died, the study said.

“These findings raise the possibility that radiation exposure from cardiac CT angiography may cause DNA damage that can lead to mutations if damaged cells are not repaired or eliminated properly,” the study said.

Photo by frankieleon

Bioengineering, Cardiovascular Medicine, Global Health, Stanford News, Technology

Stanford-India Biodesign co-founder: “You can become a millionaire, but also make a difference”

Stanford-India Biodesign co-founder: "You can become a millionaire, but also make a difference"

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

4499846308_9f084d26f0_zThe three Indian biodesign fellows who were at Stanford for the past six months have returned to New Delhi, where they’ll finish up their fellowship. They’re the last class of fellows from the Stanford-India Biodesign program, and in India they’ll be joining two teams already in progress as part of the new School of International Biodesign (SIB).

Balram Bhargava, MD, executive director of Stanford-India Biodesign (India), was at Stanford for the fellow’s final presentation of their prototype. He helped establish the relationship between Stanford and India and is now revamping the new self-sufficient program.

How did Stanford-India Biodesign originate?

I was at a retirement party in September 2006 for Ulrich Sigwart, MD, who developed the first stent. He called in some friends from all over the world, including Paul Yock, MD (director of the Stanford Biodesign Program). Paul and I shared a taxi ride to Ulrich’s vacation home and got talking. That’s when the program started. By January 2008 the first batch of fellows was here.

The basic intent was to start this innovative program in India and ultimately make it self-sufficient. We selected students from India and sent them to Stanford, then they finished out their fellowship in India.

How has the program changed over the years?

Our early fellows returned from Stanford with high-end ideas such as robots. I had to pull them all down back to the ground. My role was to give this program a soul, and I think I have been successful at that. After a few years Stanford also accepted that frugal design was the right thing for the world and I’m happy about that.

Many of our students had the intention of setting up a company and becoming millionaires. We’ve given them the idea that you can become a millionaire, but at the same time you can make a difference. That’s the delicate balance we want to teach. The students have been very bright and many of them have really delivered on this dream.

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Cardiovascular Medicine, Stanford News, Technology

Stanford-India Biodesign fellows develop prototype device to improve success of pacemaker implants

Stanford-India Biodesign fellows develop prototype device to improve success of pacemaker implants

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

IMG_6136 560When the Indian biodesign fellows observed a pacemaker implantation earlier this year, the surgeon spent four hours trying to firmly insert wires from the pacemaker into the heart muscle. Even after a painstaking surgery, the wires fall out in about five percent of cases. That’s an expensive and risky problem.

The team’s solution, which was officially revealed at the biodesign symposium last week, is a device made of popsicle sticks and a spring that attaches to the long wire that screws into the heart. The spring records the amount of force a surgeon uses when screwing in the wire. If it records a higher force, that likely means the screw went firmly into the heart muscle. A lower force means it might not have inserted well and the surgeon should try again.

The team presented their prototype to an audience of faculty, the program’s alumni and local business leaders. Harsh Sheth, MD, said their inexpensive solution to a widespread problem met with good reviews. “We were strongly encouraged to continue developing this,” he said. The team needs to finish their fellowship, but they say they might return to the idea when they are done.

Sheth and his fellow teammates Shashi Ranjan, PhD, and Debayan Saha, all had prior experience in either surgery or engineering but had never been through a deliberative process that would result in a device that combines medical needs, engineering expertise and business sense.

They’ll take their newfound skills back to India, where they’ll start the process over in the second phase of their fellowship. Their departure marks the end of Indian biodesign fellows spending immersive time at Stanford. Ranjan told me that he’s glad he applied to the program when he did rather than waiting a year, when he would have done the entire program in India.

“Being at Stanford was an amazing experience,” he said. “We had access to Silicon Valley, business, technology. We don’t have anything like that [at home].” In the future, fellows might visit the U.S. or other partner countries for shorter stays, and Stanford fellows will have opportunities to learn about biodesign in India.

Previously: Success breeds success: Early innovators in India created a sense of possibilityA jugaad for keeping pacemakers in placThe next challenge for biodesign: constraining health-care costs and Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India
Photo by Amy Adams

Cardiovascular Medicine, Medical Apps, Precision health, Research, Stanford News, Technology

MyHeart Counts shows that smartphones are catching on as new research tool

MyHeart Counts shows that smartphones are catching on as new research tool

using iPhone - 560

In the three months since Stanford researcher and cardiologist Michael McConnell, MD, told ABC’s Nightline that the new MyHeart Counts iPhone app would give scientists “a whole new way to do research,” the number of users has continued to steadily climb.

“Traditionally reaching many people to participate in research studies is quite challenging,” McConnell told business correspondent Rebecca Jarvis in March. “The ability to reach people through their phone is one major advance.”

The number of iPhone owners who have downloaded the app and consented to participate in a large-scale study of the human heart has now reached 40,000. In an effort to keep updated on how the app is progressing as a new research method, I reached out to McConnell, the lead investigator of the study, with a few questions. The MyHeart Counts study continues to break ground as a new method for reaching large numbers of research participants in a short amount of time, McConnell told me. Comparing it to traditional research trials, he said:

There have been larger research studies, particularly national efforts to study their populations, but we believe enrolling this many participants in such a short time frame is unprecedented.

The app, which was launched in early March, collects data about users’ physical activity using the smartphone’s built-in motion sensors. Participants also answer surveys concerning their cardiac-risk factors. In return, they get coaching tips and feedback on their chances of developing heart disease.

McConnell says that the next phase of the project, which will use behavior-modification methods to encourage healthy behaviors, is about to be launched. App users will be given more personalized feedback about their individual behaviors and risk, based on the American Heart Association’s Life’s Simple 7 guidance. Future tips will include messages on everything from how to manage blood pressure, eat better, lose weight and control blood sugar. Part of the study is to determine whether these type of “pings” used through apps are actually successful at changing human behavior, McConnell told me:

Healthy behaviors are critical to preventing heart disease and stroke, so the MyHeart Counts app will study which motivational tools are most helpful. This will follow the second activity and fitness assessment… The initial approach will be empowering participants with more personalized feedback about their individual behaviors and risk.

To sign up for the MyHeart Counts study, visit the iTunes store.

Previously: Lights, camera, action — Stanford cardiologist discusses MyHeart counts on ABC’s Nightline, Build it (an easy way to join research studies) and the volunteers will comeMyHeart Counts app debuts with a splash and Stanford launches iPhone app to study heart health
Photo by Japanexperterna (CC BY-SA)

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