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Cardiovascular Medicine

Cardiovascular Medicine, Research, Stanford News, Stem Cells

Tension helps heart cells develop normally, Stanford study shows

Tension helps heart cells develop normally, Stanford study shows

heart_newsTension might not be fun for us, but it looks like it’s critical for our hearts. So much so that without a little tension heart cells in the lab fail to develop normally.

This is a finding that took a mechanical engineer looking at a biological problem to solve. For many years now scientists have been able to mature stem cells into beating clumps of cells in the lab. But although those cells could beat, they didn’t do it very well. They don’t produce much force, can’t maintain a steady rhythm and would be a failure at pumping actual blood.

Beth Pruitt, PhD, a Stanford mechanical engineer, realized that in our bodies heart cells are under considerable tension, and thought that might be critical to how the cells develop.

She and postdoctoral scholar Alexandre Ribeiro started investigating how heart cells matured in different shapes and under different amounts of tension. They found a combination that produces normal looking cells with strong contractions.
The work could be useful for scientists hoping to replace animal heart cells as the gold standard for identifying heart-related side effects of drugs. Those cells are quite different from our own and often fail to detect side effects that could damage hearts in people taking the drug.

In my story about the work, I quote Ribeiro saying, “We hope this can be a drop-in replacement for animal cells, and potentially instead of having to do individual recordings from each cell we could use video analysis.”

Previously: A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells and “Clinical trial in a dish” may make common medicines safer, say Stanford scientists
Photo by Alexandre Ribeiro

Big data, Cardiovascular Medicine, Health Policy, NIH, Precision health, Public Health

The diagnostic odyssey

The diagnostic odyssey

Sick-girl-christian-krohg-1881Imagine developing some odd symptoms, like a rash and an ache. You go to the doctor and she shrugs it off and says they are probably unrelated and to come back if the rash doesn’t go away. Two months later, the rash is gone but the ache is worse. You go back and she sends you to physical therapy and suggests a specialist. A month later, neither has identified a problem. The physical therapist suspects you aren’t doing the exercises and the specialist suggests you see a psychiatrist about depression. The rash is back, too. And you are tired all the time.

For some people this frustrating and scary lack of diagnosis and care can go on for years. Sometimes, doctors have overlooked a common disease that just manifests oddly. But often, the patient has a rare disease their doctors have never heard of, let alone seen.

Yesterday, NIH launched a new Undiagnosed Diseases Network, consisting of seven major medical centers where select patients with no diagnosis can go — at no cost — for the best diagnostic facilities available. Together, the seven centers, one of which is at Stanford Medicine, magnify that network of expertise to consider patients’ cases.

Euan Ashley, MRCP, DPhil, associate professor of cardiovascular medicine and of genetics at Stanford Medicine, is co-chair of the UDN steering committee. Recently, he spoke to me for a Q&A about the new network, which is open for business. And more information on the Stanford Center for Undiagnosed Diseases can be found here.

Previously: NIH network designed to diagnose, develop possible treatments for rare, unidentified diseases and Using crowdsourcing to diagnose medical mysteries
Photo by Christian Krohg, 1881, from Wikimedia Commons

Cardiovascular Medicine, Chronic Disease, Science, Stanford News, Stem Cells

Patching broken hearts: Stanford researchers regrow lost cells

Patching broken hearts: Stanford researchers regrow lost cells

Design 1_2Most heart attack survivors face a long and progressive course of heart failure due to damage done to the heart muscle. Now, in a study published in the journal Nature, researchers are reporting a method of delivering a missing protein to the lining of the damaged heart that regenerates heart muscle cells — cardiomyocytes — killed off during a heart attack.

The study, which was conducted in animal models, offers hope for future treatments in humans, according to the senior author of the study. “This finding opens the door to a completely revolutionary treatment,” Pilar Ruiz-Lozano, PhD, told me. “There is currently no effective [way] to reverse the scarring in the heart after heart attacks.”

The delivery system that researchers used in this study is a biodesigned tissue-like patch that gets stitched directly onto the damaged portion of the heart. The protein Fstl1 is mixed into the ingredients of the patch, and the patch, made of an acellular collagen, eventually gets absorbed into the heart leaving the protein behind. Our press release explains how the patch came to be:

The researchers discovered that a particular protein, Fstl1, plays a key role in regenerating cardiomyocytes. The protein is normally found in the epicardium — the outermost layer of cells surrounding the heart — but it disappears from there after a heart attack. They next asked what would happen if they were to add Fstl1 back to the heart. To do this, they sutured a collagen patch that mimicked the epicardium to the damaged muscle. When the patch was loaded with Fstl1, it caused new cardiomyocytes to regenerate in the damaged tissue.

In reading over the study, I was particularly interested in what an engineered tissue-like patch applied to a living heart looked like – and how exactly the patch got made. I called one of the study’s first authors and went to see him in his lab.

Vahid Serpooshan, PhD, a postdoctoral scholar in cardiology at Stanford, told me he can make a patch in about 20 minutes. It’s a bit like making Jell-O, he said; collagen and other ingredients get mixed together then poured into a mold. Serpooshan uses molds of various sizes depending on what kind of a heart the patch will be surgically stitched onto.

“The damaged heart tissue has no mechanical integrity,” Serpooshan said. “Adding the patch is like fixing a tire… Once the patch is stitched onto the heart tissue, the cardiac cells start migrating to the patch. They just love the patch area…”

Previously: Stanford physician provides insight on use of aspirin to help keep heart attacks and cancer away, Collagen patch speeds healing after heart attacks in mice and Big data approach identifies new stent drug that could help prevent heart attacks
Image, of a patch stitched to the right side of the heart, by Vahid Serpooshan

Cardiovascular Medicine, Chronic Disease, Women's Health

Surviving a betrayal of the heart

Surviving a betrayal of the heart

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from a patient with spontaneous coronary artery dissection (SCAD).

2259323415_ab113de5bc_zThis is a story about a betrayal of the heart — an actual heart. Girl has heart, girl treats heart well, heart gets torn up and girl figures out how to recover from this betrayal by her own body.

Last summer, I participated in my second sprint triathlon. The first part was a half-mile swim in a cold lake. I’d been swimming this distance for months and had done this same triathlon before. Yet, I couldn’t catch my breath, my chest hurt and swimming was appallingly hard for me. But I persevered and finished the biking and running events just fine.

Two weeks later, unnerved by my unsuccessful swim, I steeled myself for a similar swim across a lake in Idaho. Almost halfway through my swim, I started struggling to breathe and felt a band of pain and searing cold across my sternum. I felt weak and cold and couldn’t swim anymore.  Fortunately, my husband was on a paddleboard close by. I called him over, climbed on the board and hung onto his ankles for dear life (vomiting occasionally) as he paddled us to shore.

In retrospect, I had many of the typical symptoms women experience when having heart attack, but it took a while before it dawned on us that I was suffering from one. I don’t fit the profile: I was 53, nearly vegetarian, slim, fit with a mild addiction to kale smoothies. However, I had just gone through menopause and was on a low dose of HRT.

Fortunately, the ER doctor in Idaho did an EKG and figured out I was having a heart attack. The next day, an angiogram found a tear in the innermost wall of my coronary artery called a spontaneous coronary artery dissection (SCAD). This tear causes blood to flow between the layers of the arterial wall, blocking blood flow and causing a heart attack. SCADs are rare, yet, nearly 80-90 percent of SCAD patients are women in their early 40s with no additional risk factors.

It’s not yet known what causes SCADs. So, I am left with a lot of unanswered questions, and I’ve had to slowly rebuild trust in my own body and abilities, knowing my condition is rare and poorly understood.

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Cardiovascular Medicine, Chronic Disease, Health and Fitness, NIH, Research, Stroke

NIH-funded study shows effectiveness of intensive blood pressure management

NIH-funded study shows effectiveness of intensive blood pressure management

blood pressure reading2This morning the National Institutes of Health announced that it halted a clinical trial on high blood pressure in order to share the results publicly right away. According to the initial study findings, managing high blood pressure so it falls below a specific blood pressure target significantly reduces rates of cardiovascular disease and lowers risk of mortality.

The Systolic Blood Pressure Intervention Trial, commonly called SPRINT, is the largest known study of its kind to examine how holding systolic blood pressure below the currently recommended level affects cardiovascular and kidney diseases.

For this trial, nearly 100 medical centers in the United States and Puerto Rico, including Stanford, recruited more than 9,300 participants age 50 and older for a study that involved carefully adjusting the amount or type of blood pressure medication to achieve a target systolic pressure of 120 millimeters of mercury (mm Hg).

As outlined in an NIH press release, the researchers found that reducing systolic pressure to 120 mm Hg or less, reduced rates of stroke, heart attacks, heart failure and other cardiovascular events by almost a third and reduced the risk of death by almost a quarter, compared to the target systolic pressure of 140 mm Hg.

“SPRINT addressed a fundamental question faced by internal medicine physicians, nephrologists, cardiologists and other specialists – that is, how low should our blood pressure target be?” said Glenn Chertow, MD, MPH, principal investigator for the Stanford site.

Although researchers have known for some time that lowering patients’ blood pressure can improve survival rates and reduce their chances of having a stroke, heart disease or a kidney-related event, studies that link these benefits to a specific blood pressure were lacking. This is why the SPRINT study is so important.

“Before today there was no evidence from randomized clinical trials to demonstrate that lowering systolic blood pressure toward or below 120 mmHg was safe and effective,” Chertow told me yesterday afternoon.

“Adoption of the approach learned from SPRINT could change medical practice and materially improve the public health,” Chertow continued. “We’re proud to have participated” in the study.

Previously: The importance of knowing your blood pressure level in preventing hypertensionUltra-thin flexible device offers non-invasive method of monitoring heart health, blood pressureAsk Stanford Med: Stanford interventional cardiologist taking questions on heart health and High-quality chocolate linked to lower risk of heart failure
Photo by World Bank Photo Collection

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.

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