Published by
Stanford Medicine

Category

Cardiovascular Medicine

Cardiovascular Medicine, Research, Videos

Researchers capture detailed three-dimensional images of cardiac dynamics in zebrafish

Researchers capture detailed three-dimensional images of cardiac dynamics in zebrafish

The stunning video above depicts a reconstructed beating heart of a zebrafish embryo with the muscle layer shown in red and the endothelium highlighted in blue. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Germany created the video using a new three-dimensional imaging technique, which holds the promise of leading to a better “understanding of congenital heart defects as well in future experiments on cardiac function and development”. As explained in a release:

[Researchers] developed a high-speed, selective plane illumination microscope that manages to do just that. By gently illuminating the fish heart with a thin light sheet and observing the emitted fluorescence with a fast and sensitive camera the researchers have achieved fast, non-invasive imaging of labelled heart tissue. The process involves taking multiple movies, each covering individual planes of the heart (movie stacks), then using the correlations between the individual planes to generate a synchronised, dynamic 3D image of the beating heart.

“These renderings allow us to further follow characteristic structures of the heart throughout the cardiac cycle,” says Michaela Mickoleit, PhD student who performed the experiments in [Jan Huisken's] lab.

Via Medgadget
Previously: An advancement in optogenetics: Switching off cells with light now as easy as switching them on and New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics

Cardiovascular Medicine, Genetics, Research, Stanford News

Stanford patient on having her genome sequenced: “This is the right thing to do for our family”

Stanford patient on having her genome sequenced: "This is the right thing to do for our family"

genomicsImagine you were diagnosed, seemingly out of the blue, with hypertrophic cardiomyopathy, a condition that is caused by mutations in genes involved in the heart’s muscle cells and is the most common cause of sudden death in young people. If given the chance, would you have your entire genome analyzed to understand more about your genetics and the condition? That’s the decision Julie Prillinger faced and, in the end, she embraced the opportunity to untangle the mystery of her DNA. “This is the right thing to do for our family – and our friends and family have been very supportive,” she said in a Stanford Medicine News story.

As described in the piece, Prillinger’s genome was among the first to be sequenced through a pilot program of the new Clinical Genomics Service at Stanford Hospital & Clinics. The pilot phase of the service is limited to specific patient groups, including: children with mystery diseases, patients with unexplained hereditary cancer risk, patients with inherited cardiovascular or neurological disease and those with severe, unexplained drug reactions. More details about the service from the article:

Stanford’s service will apply a highly integrated approach that includes professional genetic counseling, the most advanced genome sequencing technology available, and expert interpretation by molecular genetic pathologists and other physicians with expertise in this emerging and complex field.

The new service will be tied closely to other diagnostic genetic testing programs currently offered at the two hospitals. Those programs, which include molecular genetic pathology, cytogenetics and clinical biochemical genetics, have an outstanding record of compliance with the extensive regulatory requirements for diagnostic genetic testing.

In addition to providing Prillinger and her family with crucial information about their personal health, the results could reveal undiscovered information related to the condition encoded in the human genome, which may enable the expansion of current tests.

Previously: Using genetic testing to enhance students’ knowledge of personalized medicine, Ask Stanford Med: Genetics chair answers your questions on genomics and personalized medicine and Direct-to-consumer genetic testing: A commentary

Cardiovascular Medicine, Genetics, Patient Care, Pediatrics, Research, Stanford News

When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn

When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn

8963661410_d59cc4c08f_z

It’s an ‘edge-of-your-seat’ story: The newborn’s heart had stopped multiple times in the hours since her birth. Her doctors at Lucile Packard Children’s Hospital Stanford had tried everything to help her, but her situation was dire.

The baby had an unusually severe form of an inherited cardiac condition called long QT syndrome. The syndrome, which is most often diagnosed in older children or adults, can be caused by a mutation in any of several genes; until the doctors knew exactly which genetic mutation was causing the condition they wouldn’t know what drug would be most likely to help. The stakes were high: by her second day of life she’d received an implantable defibrillator and several intravenous drug infusions.

As cardiologist Euan Ashley, MD, PhD, explained to me:

The team literally tried everything we could think of to help this child, including trying every drug that could possibly make a difference. It was a heroic effort by a very diverse group of professionals.

The clinicians and researchers, including pediatric cardiologist Scott Ceresnak, MD, who managed the baby’s clinical care, realized it was critically important to identify the baby’s disease-causing mutation to learn which drug would be best for her. To do so, they dropped everything else they were doing and sequenced her entire genome to pinpoint the culprit within just ten days – an unprecedented feat. Ashley, who directs Stanford’s new Clinical Genomics Service as well as its  Center for Inherited Cardiovascular Disease, and pediatric cardiology fellow James Priest, MD, recently published the case study in the journal Heart Rhythm.

This is the future of genetic testing and we hope, the future of medicine.

Using customized commercial software and tools developed at Stanford, the researchers were able to zero in on a mutation in a gene called KCNH2 known to be associated with long QT. They also found another, novel mutation in a gene involved in determining the structure of the heart during development.

As Priest explained in an e-mail to me:

Whether it is a CT scan, x-ray, or genetic test, we work hard to make a diagnosis as quickly as possible when there is a critically-ill baby under our care. Whole genome sequencing returned this diagnosis in days instead of weeks. We were able to turn the raw sequence data into a diagnosis in about 12 hours.

Continue Reading »

Cardiovascular Medicine, Genetics, In the News, Research, Science, Stanford News

A simple blood test may unearth the earliest signs of heart transplant rejection

A simple blood test may unearth the earliest signs of heart transplant rejection

2123984831_b7d09079a4_oIs there an organ more precious than a donated heart? Heart transplant recipients would likely say no. But, in order to keep their new heart healthy, they have to identify any signs of rejection as early as possible. Unfortunately (and ironically), the gold standard procedure to detect rejection – repeated heart biopsies – involves snipping away and analyzing tiny bits of tissue from the very organ they waited so long to receive. The procedure is also uncomfortable, and can cause complications.

Now, Stanford bioengineer Stephen Quake, PhD, and his colleagues have found that a simple blood test that detects donor DNA in the bloodstream of the recipient can detect signs of rejection far earlier than biopsy. Their results were published today in Science Translational Medicine.

From our release:

The study of 65 patients (21 children and 44 adults) extends and confirms the results of a small pilot study completed in 2011 by the Stanford researchers. Whereas the earlier study used stored blood samples and medical histories from seven people, the new study followed patients in real time before and after transplant. The researchers directly compared the results of simultaneously collected biopsies and blood samples, and tracked how the values changed during the rejection process.

The blood test takes advantage of the fact that dying heart cells release genetic material into the recipient’s blood. Any increase beyond a normal baseline level indicates a possible attack by the immune system on the donated organ. As described in our release:

In the pilot study of 2011, the researchers first used the presence of the Y chromosome to track the donor DNA when a woman received a heart from a male donor. Then they hit upon using differences in SNPs instead; this method doesn’t require a gender mismatch between donor and recipient. They found that, in transplant recipients not experiencing rejection, the donor DNA accounted for less than 1 percent of all cell-free DNA in the recipient’s blood. During rejection episodes, however, the percentage of donor DNA increased to about 3 or 4 percent.

In the new study, the researchers monitored 565 samples from the 65 patients to assess the assay under real-time clinical conditions. They found they were able to accurately detect the two main types of rejection (antibody-mediated rejection and acute cellular rejection) in 24 patients who suffered moderate to severe rejection episodes, one of whom required a second transplant. They were also able to detect signs of rejection up to five months before the biopsies indicated anything troubling.

The test will still need to be optimized for regular clinical use. However, cardiologist Kiran Khush, MD, a co-senior author of the study, explained what the advance could mean to heart transplant recipients:

This test has the potential to revolutionize the care of our patients… It may also allow us to conduct several diagnostic tests simultaneously. For example, we could also look for microbial sequences in the blood sample to rule out infection or other complications sometimes experienced by transplant recipients. It could allow us to determine whether shortness of breath experienced by a patient is due to an infection or the start of a rejection episode. It could be a one-stop shop for multiple potential problems.

Full disclosure: Stanford has applied for a patent relating to the test described in this study. Quake is a consultant for and holds equity in CareDX Inc., a molecular diagnostics company that has licensed a patent from Stanford related to a method used in the study and is developing it for clinical use.

Previously: ‘Genome transplant’ concept helps Stanford scientists predict organ rejection, Stanford study in transplant patients could lead to better treatment and New techniques to diagnose disease in a fetus
Photo by Desi

Cardiovascular Medicine, Immunology, Research, Science, Stanford News, Stem Cells

Oh, grow up! “Specialized” stem cells tolerated by immune system, say Stanford researchers

Oh, grow up! "Specialized" stem cells tolerated by immune system, say Stanford researchers

3075268200_419b9e73b7_zMany of us know by now that stem cells are remarkably fluid in the types of cells they can become. But this fluidity, or pluripotency, comes with a price. Several studies have shown that the body’s immune system will attack and reject even genetically identical transplanted stem cells, making it difficult to envision their usefulness for long-term therapies.

Now Stanford cardiologist Joseph Wu, MD, PhD, and his colleagues have shown that coaxing the stem cells to become more-specialized (a process known as differentiation) before transplantation allows the body to recognize and tolerate the cells. Their research was published today in Nature Communications (subscription required).

From our release:

In a world teeming with microbial threats, the immune system is a necessary watchdog. Immune cells patrol the body looking not just for foreign invaders, but also for diseased or cancerous cells to eradicate. The researchers speculate that the act of reprogramming adult cells to pluripotency may induce the expression of cell-surface molecules the immune system has not seen since the animal (or person) was an early embryo. These molecules, or antigens, could look foreign to the immune system of a mature organism.

Previous studies have suggested that differentiation of iPS cells could reduce their tendency to inflame the immune system after transplantation, but this study is the first to closely examine, at the molecular and cellular level, why that might be the case.

Postdoctoral scholars Patricia Almeida, PhD, and Nigel Kooreman, MD, and assistant professor of medicine Everett Meyer, MD, PhD, share lead authorship of the study. They found that laboratory mice accepted grafts of endothelial cells made from stem cells much more readily than they did the stem cells themselves. As Wu, who also directs the Stanford Cardiovascular Institute said in our release:

This study certainly makes us optimistic that differentiation — into any nonpluripotent cell type — will render iPS cells less recognizable to the immune system. We have more confidence that we can move toward clinical use of these cells in humans with less concern than we’ve previously had.

Previously: New technique prevents immune-system rejection of embryonic stem cells and Overcoming immune response to stem cells essential for therapies, say Stanford researchers
Photo by Umberto Salvagnin

Cardiovascular Medicine, Public Health, Stanford News

The importance of knowing your blood pressure level in preventing hypertension

The importance of knowing your blood pressure level in preventing hypertension

blood_pressure_051414One in three adults in the United States has high blood pressure, also known as hypertension, and less than half of those diagnosed with the condition have it under control, according to data from the Centers for Disease Control and Prevention.

In a recent Be Well Q&A, Sandra Tsai, MD, a clinical assistant professor of medicine and cardiovascular medicine at Stanford Hospital and Clinics, discusses why it’s crucial to get regular blood pressure screenings. She says, “Hypertension is preventable and treatable; therefore, it is imperative that people know their blood pressure level.” When asked what she would like to change about public awareness of hypertension, she said:

I want people to understand the importance of knowing their blood pressure readings and the definition of a normal reading. It is also important for people to know that hypertension often does not produce symptoms. Therefore, we all need to have our blood pressure checked regularly so that if hypertension is occurring, it will be detected early.

There are many things people can do to prevent or alleviate hypertension; thus, if diagnosed, such individuals should talk with their medical provider for help with behavior change and the possible need for anti-hypertensive medication.

Previously: Why it’s “vitally important” to monitor your blood pressure, Ask Stanford Med: Stanford interventional cardiologist taking questions on heart health and Stanford Hospital & Clinics introduces month-long heart health challenge
Photo by Tunstall

Cardiovascular Medicine, Health and Fitness, In the News

Examining how prolonged high-intensity exercise affects heart health

Examining how prolonged high-intensity exercise affects heart health

woman running near mountain

Emerging scientific evidence points to a possible threshold of intensity, duration or distance that if crossed could limit the benefits of physical activity. A pair of new studies in the journal Heart raise concerns that prolonged, extreme exercise could negatively affect heart health for certain groups.

In the first study, German researchers followed more than 1,000 people with stable heart disease for a decade. Participants’ exercise habits ranged from less than two times a week to more than four times a week. WebMD reports that researchers found:

Compared to those who got regular exercise, the most inactive people were about twice as likely to have a heart attack or stroke, and were about four times more likely to die of heart disease and all causes, the researchers said.

However, Mons’ team also found that those who did the most strenuous daily exercise were more than twice as likely to die of a heart attack compared to those who exercised more moderately.

For the second study, Swedish researchers evaluated the potential of endurance exercise to increase the risk of atrial fibrillation. It included 44,000 men who were surveyed about their previous levels of physical activity certain ages and then had their heart health monitored for 12 years. More from the article:

Those who had done intensive exercise for more than five hours a week when they were younger were 19 percent more likely to have developed a heart rhythm disorder called atrial fibrillation by age 60 than those who exercised for less than an hour a week.

That risk increased to 49 percent among those who did more than five hours of exercise at age 30 but did less than an hour a week by the time they were 60. Participants who cycled or walked briskly for an hour or more a day at age 60 were 13 percent less likely to develop atrial fibrillation.

Authors of an accompanying editorial concluded that “the benefits of exercise are definitely not to be questioned,” and that the findings could be useful to “maximize benefits obtained by regular exercise while preventing undesirable effects.”

Previously: Lack of exercise shown to have largest impact on heart disease risk for women over 30, Study reveals initial findings on health of most extreme runners, Is extreme distance running healthy or harmful? and Untrained marathoners may risk temporary heart damage
Photo by Robin McConnell

Cardiovascular Medicine, Health and Fitness, Research, Women's Health

Lack of exercise shown to have largest impact on heart disease risk for women over 30

Lack of exercise shown to have largest impact on heart disease risk for women over 30

woman_running_londonHeart disease, stroke or another form of cardiovascular disease claims the life of someone’s wife, mother, daughter or sister every minute in the United States, according to statistics from the American Heart Association. Now a study shows that an inactive lifestyle outweighs other risk factors, such as obesity and smoking, for developing cardiovascular disease among women age 30 and older.

In the study, Australian researchers tracked the health of more than 30,000 women born in the 1920s, 1940s and 1970s. Findings showed that for women under the age of 30, smoking had the most significant impact on women’s risk of heart disease. But as women got older, and kicked their nicotine habit, the biggest factor shifted to lack of exercise. According to a recent MedPage Today story:

The results highlight the fact that population attributable risks for heart disease appear to change throughout women’s lives, the researchers concluded.

The study findings highlight the importance of emphasizing regular exercise for reducing cardiovascular disease risk, especially in young adulthood and middle age, the researchers said.

“Our data suggest that national programs for the promotion and maintenance of physical activity, across the adult lifespan, but especially in young adulthood, deserve to be a much higher public health priority for women than they are now,” they wrote.

They estimated that “if every woman between the ages of 30 and 90 were able to reach the recommended weekly exercise quota — 150 minutes of at least moderate intensity physical activity — then the lives of more than 2,000 middle-age and older women could be saved each year in Australia alone.”

Previously: Study shows many women have a limited knowledge of stroke warning signs, More evidence that prolonged inactivity may shorten life span, increase risk of chronic disease, Exercise is valuable in preventing sedentary death and Ask Stanford Med: Cardiologist Jennifer Tremmel responds to questions on women’s heart health
Photo by James Roberts

Cardiovascular Medicine, Emergency Medicine, Patient Care, Pregnancy, Research, Stanford News

Cardiac arrest in pregnancy: New consensus statement addresses CPR for expectant moms

Cardiac arrest in pregnancy: New consensus statement addresses CPR for expectant moms

pregnantbelly2When a pregnant woman’s heart stops, two lives are threatened. Yet few caregivers know how to modify their cardiopulmonary resuscitation technique for the expectant mom and her fetus, and few hospitals are optimally prepared for such an event.

To fill the knowledge gap, the Society for Obstetric Anesthesia and Perinatology commissioned a Stanford-led team of experts from several medical disciplines to write a consensus statement of expert recommendations, publishing in the May issue of Anesthesia & Analgesia, that describes best practices for CPR on a pregnant patient. The new statement is one of many examples of Stanford leadership in helping to save the lives of pregnant women around the world; our experts have also helped to develop widely-adopted protocols for dealing with massive hemorrhage during delivery and for treatment of pre-eclampsia, for example.

I asked two Stanford scientists who helped prepare the statement, lead author Steven Lipman, MD, and senior author Brendan Carvalho, MD, for their perspectives on the challenges of resuscitation in pregnancy. Both are obstetric anesthesiologists at Lucile Packard Children’s Hospital Stanford, where Carvalho is chief of obstetric anesthesia.

“The good news is that cardiac arrest in pregnancy is very rare, and also that rates of survival are higher than for the non-pregnant population,” Lipman said. Only about one in every 20,000 women with access to modern obstetric care experiences cardiac arrest while pregnant. Higher survival among pregnant patients may be partly due, he said, to the fact that many maternal cardiac arrests are witnessed: They tend to occur during labor or delivery, when the woman is already in a hospital and being closely monitored by trained medical staff who can begin CPR right away.

But rarity creates challenges. Because maternal cardiac arrests happen infrequently, obstetric caregivers have less experience in performing resuscitation than people who work in other parts of the hospital, such as the emergency room or intensive care unit. And it’s impossible to conduct randomized clinical trials – usually considered the gold standard for evidence-based medicine – on these emergencies to determine what works best.

“Also, in pregnancy, there is an asymmetry between people’s expectations and the reality of the risk,” Lipman said. “People think, ‘Oh, I’m just having my baby, it’s just natural.’ But if you look at third-world countries with no developed medical infrastructure, the rates of maternal mortality are extremely high. Yes, it’s natural and people expect an easy delivery and a healthy baby, but the reality is that it can be a risky process, and people can become critically ill very quickly.”

The physiology of pregnancy also presents challenges for resuscitation. During the second half of pregnancy, when a pregnant woman lies flat on her back, the fetus and the enlarged uterus compress the large vein that returns most of the blood to her heart. This decreases the amount of blood available to the heart and makes it harder to provide effective chest compressions in CPR. And resuscitators also must think about how to balance the needs of the mother with those of the fetus.

Continue Reading »

Cardiovascular Medicine, Nutrition, Science

What’s not to love? Chocolate’s feel-good chemicals

Cabdury2Spring is here and symbols of new life abound. If Cadbury Cream Eggs (yes, gross, but I love them anyway) and Mini Eggs on drugstore shelves have you, too, thinking about chocolate, check out this piece in the Washington Post on the history and chemistry of the “feel-good” components of the stuff, including “the world’s most widely consumed psychoactive drug,” caffeine.

Chemist Simon Cotton, PhD, writes:

Another chocolate molecule believed to be important was discovered less than 20 years ago: anandamide. This binds to receptors in the brain known as cannabinoid receptors. These receptors were originally found to be sensitive to the most important psychoactive molecule in cannabis, Δ9-THC. Likewise, anandamide and similar molecules found in chocolate are also thought to affect mood.

Phenylethylamine, another family of chemicals, is found in chocolate in very small amounts. It is a naturally occurring substance with a structure that is closely related to synthetic amphetamines, which of course, are also stimulants. It is often said that our brain produces phenylethylamine when we fall in love. It acts by producing endorphins, the brain’s natural “feel-good” molecules. The bad news, however, is that eating chocolate is probably not the best way of getting our hands on phenylethylamine as enzymes in our liver degrade it before it can reach the brain.

There are other molecules in chocolate – especially in dark chocolate – such as flavonoids, which some scientists think may help improve cardiovascular health. But chocolate manufacturers have been known to remove bitter flavanols from dark chocolate.

One last feel-good factor, which isn’t a molecule: the melt-in-your mouth sensation. The fatty triglycerides in cocoa butter can stack together in six different ways, each resulting in a different melting point. Only one of these forms has the right melting point of about 34 degrees, so that it “melts in your mouth, not in your hand.” Getting the chocolate to crystallize to give this form is the product of very careful chocolate engineering.

I’m curious to know what kinds of chemicals give the sugary “whites” and “yolks” of the cream eggs their appeal, though maybe it’s better kept a foil-wrapped secret.

Previously: When caffeine dependence affects quality of lifeDo you (heart) chocolate? Evaluating the cocoa “prescription” for cardiac health and Mapping the DNA of wild strawberries and fine chocolate
Photo by Joel Kramer

Stanford Medicine Resources: