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Cardiovascular Medicine

Cardiovascular Medicine, Medical Education, Patient Care, Stanford Medicine Unplugged

Pathology vs. patients: Balancing morbid fascination with heart-felt care

Pathology vs. patients: Balancing morbid fascination with heart-felt care

Stanford Medicine Unplugged (formerly SMS Unplugged) is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week during the academic year; the entire blog series can be found in the Stanford Medicine Unplugged category.

3690107655_eef7c24702_zI recently saw a patient who, against all odds, survived an aortic dissection. Miraculously, he was alive after the wall of his aorta — the largest and most important vessel in the body — began to rip apart. Aortic dissections are so violent and agonizing that a large portion of these patients don’t survive. Yet somehow, my patient was still able to sit upright in his chair and recount his story to me just a day after his surgery, a testimony to how far medicine has advanced and to how lucky he was.

I admit that I was more fascinated by his cardiovascular travails than I was concerned by his suffering and the long road of recovery awaiting him. After all, it was only a few months prior that we learned the pathophysiology of aortic dissections. And now in front of me was a real life case study accompanied by authentic lab values, imaging, and physical exam findings, all of which were free for me to probe.

Had I encountered him prior to medical school, I would have spent more time to express words of support and sympathy — he’s a survivor and he needed any and all means of encouragement to return to some semblance of normalcy.

Once we have reached the end of the journey, the patient himself is buried underneath our medical knowledge and the disease has seized all our attention.

But medical school, for better or worse, changes your perception of patients and their plights. Despite all the efforts in the curriculum to teach us to view the patient as a whole, the endless nights and sacrificed weekends of burying ourselves in textbooks and scrambled jargon eventually dehumanizes patients and forces the spotlight on the pathology.

Call it insensitivity or callousness, but this morbid fascination with human illness is one of the paradoxes in medicine — that we must sympathize with the patient as well as with the disease that is harming him and may eventually kill him.

And for better or worse, becoming a competent doctor requires some modicum of this perverse curiosity, a veritable double-edged sword. Anyone who lacks it would simply not be able to survive four years of college dedicated mostly to studying basic biology, another four years of medical school to studying clinical presentations, and then finally another handful of years to specialize, all the while taking on hundreds of thousands of dollars in debt and sacrificing young adulthood. Yet, insidiously, once we have reached the end of the journey, the patient himself is buried underneath our medical knowledge and the disease has seized all our attention.

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Cardiovascular Medicine, Chronic Disease, Dermatology, Research, Stanford News

Limb compression device reduces skin infections caused by lymphedema

Limb compression device reduces skin infections caused by lymphedema

Key among the nasty problems caused by lymphedema, a common cardiovascular disease that causes limb and trunk swelling, is the risk of skin infection. Lymphedema causes the skin to thicken and become inelastic, which open the doors for infection to enter more easily; according to Stanford’s Stanley Rockson, MD, about 25 percent of lymphedema patients experience recurring infections that can result in hospitalization.

Thus the results of a recent study published in JAMA Dermatology offers some exciting news, says Rockson, a world renowned expert in lymphedema.

The fact that we saw dramatic reductions in the incidence in rate of infections… is very noteworthy

In the study, an advanced model of a pneumatic compression device used to treat lymphedema was found to reduce skin infections from the disease by nearly 80 percent. Rates of cellulitis, the medical term for such skin infections, were lowered from 21 percent to 4.5 percent in the people with lymphedema due to cancer and from 28.8 percent to 7.3 percent in individuals whose lymphedema was not due to cancer.

Pneumatic compression devices, which have been in use for decades, are inflatable garments that when applied to the swollen area of the skin inflate and deflate in cycles to help drain lymph fluid build up. Most of these devices simply apply an increasing degree of pressure from the garment, but the model used in this study goes a step further. As Rockson, a co-author on the study, explains in a podcast accompanying the journal article:

This device works not just by adding pressure… It actually intends to simulate the intervention used by physical therapists when they do manual lymphatic massage. It places very low pressure stress on the skin increasing the filling of the lymphatic capillaries and thereby stimulating intrinsic contractility.

The idea is that the distribution of the pressure can be relegated and the treatment more targeted, he says.

“The fact that we saw dramatic reductions in both the incidence in rate of infections as well as the decreases in cost-related to care, ER visits, hospitalizations, intravenous antibiotics, is very noteworthy,” Rockson concludes.

The research was conducted at the University of Minnesota School of Public Health in collaboration with Vanderbilt University School of Nursing.

Previously: Home health care treatments for lymphedema patients cut costs and improve care; New Stanford registry to track lymphedema in breast cancer patients.

Cardiovascular Medicine, Patient Care, Surgery

61-year-old grandfather gets new heart valve at Lucile Packard Children’s Hospital Stanford

61-year-old grandfather gets new heart valve at Lucile Packard Children's Hospital Stanford

Dr. George Lui, M.D., Dr. Dan Murphy, M.D., Mr. Sang Hee Yoon, Mrs. Min Wha Yoon, and Dr. Katsuhide Maeda, M.D. at Stanford Children’s Health Care on Tuesday, October 6, 2015. ( Norbert von der Groeben/ Stanford School of Medicine )One little-known fact about children’s hospitals: A number of their patients are not children.

I wrote about one such patient recently, a 61-year-old San Jose grandfather who received a new heart valve at Lucile Packard Children’s Hospital Stanford in May. Sang Hee Yoon was born in South Korea at a time when many babies with heart defects died in infancy. He was one of the first people there to receive a surgical repair for his heart condition, called tetraology of Fallot. The repair worked well for many years, but eventually he needed a replacement for a malfunctioning heart valve.

When the time came, the doctors on our adult congenital heart disease team were here to help. My story explains the unusual challenges of their field, which is growing rapidly as 20,000 teenagers with congenital heart defects “graduate” to adult medical care each year:

“Patients come back at 40 or 50 years old, telling us, ‘My doctor said I was cured,’” said George Lui, MD, medical director of the Adult Congenital Heart Program at Stanford, a collaboration between the Heart Center at Lucile Packard Children’s Hospital and Stanford Health Care. Some patients’ childhood surgical repairs were initially judged so successful that they never expected to return to a cardiologist, said Lui… In other cases, the first surgery was so unusual and risky that the surgeon discouraged the patient from undergoing further operations.

But most adults with repaired congenital heart defects are not cured, doctors have learned. As the discipline has matured, cardiologists have honed their understanding of how to help patients like Yoon navigate the risks of living with lingering heart problems, as well as learning how congenital defects interact with cardiovascular problems people acquire with age.

Mr. Yoon’s new heart valve has made a big difference – he and his wife told me that his health is better than ever before. Prior to his surgery at Stanford, his malfunctioning heart valve meant that his body never quite got enough oxygen. He often felt achy or had tightness in his chest, especially at high altitudes. All that is resolved now. The couple’s four children and 10 grandchildren are thrilled:

“They are so happy about my condition,” [Yoon] said. “Not only family members but everybody I know is saying, ‘You look so healthy!’” The Yoons have already visited Kings Canyon National Park, a destination they chose for its mountainous scenery. “I feel such gratitude that now I can enjoy my new life,” Yoon said.

Previously: Patient is “living to live instead of living to survive” thanks to heart repair surgery, Little hearts, big tools and Surgeon building a heart valve that can grow and repair itself
Photo – of Mr. and Mrs. Yoon with his doctors (from left to right) George Lui, MD, Daniel Murphy, MD, and Katsuhide Maeda, MD – courtesy of Lucile Packard Children’s Hospital Stanford

Cardiovascular Medicine, Public Health, Research, Stroke

In study, work stress linked to stroke risk

In study, work stress linked to stroke risk


High-stress jobs are known to be associated with increased risk of cardiovascular disease. A research study published last week in the journal Neurology now indicates that work stress also increases the risk of stroke, especially for women.

Dingli Xu, MD, and his research team from Southern Medical University in Guangzhou, China performed a comprehensive statistical analysis of six previous research studies on job stress and stroke risk; the studies included a total of 138,782 participants who were followed for three to 17 years. For the work they classified jobs into one of our four categories, based on the amount of control workers have over their jobs and the psychological demand of their jobs:

  • Passive jobs with low control and low demand, such as janitors and other manual laborers
  • Low-stress jobs with high control and low demand, such natural scientists and architects
  • High-stress jobs with low control and high demand, such as waitresses and nursing aids
  • Active jobs with high control and high demand, such as physicians, teachers and engineers

Xu’s team determined that people with high-stress jobs had a 22 percent increased risk of all types of stroke compared to people with low-stress jobs, while there was no increased relative risk of stroke for people with passive or active jobs. The increased risk associated with a high-stress job compared to a low-stress one was found to be even greater at 58 percent for ischemic strokes, the most common type of stroke.

Analyses were also performed separately for women and men, including more than 126,459 women and only 12,323 men. Women with high-stress jobs had a 33 percent higher risk of all types of stroke than women with low-stress jobs. However, no significant increase in relative stroke risk was seen for men with high-stress jobs, most likely due to the limited number of men included in the studies.

Similarly, the researchers calculated the increased incidence of stroke in the population associated with high-stress jobs to be 4.4 percent overall and 6.5 percent for women.

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Cardiovascular Medicine, Genetics, Research, Stanford News

Close-up look at mutinous mutant molecule implicated in hypertrophic cardiomyopathy

Close-up look at mutinous mutant molecule implicated in hypertrophic cardiomyopathy

heart failureThe healthy human heart is a hard-working muscle: Beating just over 100,000 beats per day,  it pumps five quarts of blood per minute – enough to fill three supertankers worth of blood over the course of an average person’s lifetime.

Like any other mechanical pump, the heart is made up of various components, including different kinds of proteins. One of those proteins, a “molecular motor” called cardiac myosin (there are several varieties of myosin), plays a crucial role. A myosin molecule can oscillate lengthwise, contracting and relaxing by turns. It’s the coordinated oscillations of myriad cardiac myosin molecules that are, in the aggregate, responsible for the heartbeat.

Defective cardiac myosin exacts a severe medical price. Hypertrophic cardiomyopathy, caused by mutations in a gene encoding cardiac myosin, occurs in at least one in 500 people and is a leading cause of heart failure in the United States and worldwide. It’s also the primary cause of sudden deaths due to heart attack in people under age 30.

A mutation known as R403Q, identified a couple of decades ago, ranks among the nastiest and most widely studied of literally hundreds of cardiac-myosin mutations.  The general thinking has been that the mutation results in a “gain of function,” meaning stronger-than-normal myosin contractility.

Now, researchers under the direction of Stanford biochemist Jim Spudich, PhD, have for the first time been able to look at the effects of this mutation in human cardiac myosin as opposed to animal models. Spudich, whom I wrote up in 2012 as the winner of that year’s prestigious Lasker Award for Basic Medical Research, is a pioneer in the analysis of myosin and its associated motility-related proteins. Integrating approaches drawn from cell physiology, physics, biochemistry, structural biology and genetics, Spudich and his colleagues have developed methods of  measuring the exact amount of energy consumed in each contraction of a single molecule of myosin. (In my 2012 Lasker Award write-up, I explained myosin’s critical involvement not only in heartbeat but also in all muscular movement and, indeed, all transport of molecular materiel within every living plant or animal cell.)

In a study published in Science Advances, Spudich’s team measured the effects of the R403Q mutation at the single-molecule level and was able to demonstrate tiny, but relevant changes in the power of the mutant myosin molecule.The next step is to, in an even more sophisticated way, measure these effects in a microenvironment more closely approximating that of a living human heart.

R403Q is just the first of several hypertrophic-cardiomyopathy-inducing mutations the team is analyzing, one by one, with their state-of-the-art techniques.

Previously: Stanford molecular-motor maven Jim Spudich wins Lasker Award, Sudden cardiac death has cellular cause, say Stanford researchers and Stanford patient on having her genome sequenced: “This is the right thing to do for our family”
Photo by Sharon Sinclair

Cardiovascular Medicine, Pediatrics, Pregnancy, Research

Higher blood sugar in pregnancy tied to heart defects in baby, even if mom isn’t diabetic

Higher blood sugar in pregnancy tied to heart defects in baby, even if mom isn't diabetic

five-heartsFor many years, doctors have known that women who had diabetes during pregnancy faced an increased risk of giving birth to a baby with a congenital heart defect. But now, for the first time, researchers have shown that the risk isn’t limited to women with diabetes. A new Stanford study, publishing today in JAMA Pediatrics, found that women who were carrying a fetus with tetralogy of Fallot, the most common cause of blue baby syndrome, had higher blood sugar levels on average than women carrying healthy fetuses, even if the mothers were not diabetic.

From our press release about the research:

“Diabetes is the tail end of a spectrum of metabolic abnormalities,” said James Priest, MD, the study’s lead author and a postdoctoral scholar in pediatric cardiology. “We already knew that women with diabetes are at significantly increased risk for having children with congenital heart disease. What we now know, thanks to this new research, is that women who have elevated glucose values during pregnancy that don’t meet our diagnostic criteria for diabetes also face an increased risk.”

The Children’s Heart Center at Lucile Packard Children’s Hospital Stanford (where Priest, who is also a pediatric cardiology fellow, sees patients) is already a world leader in treating children born with tetralogy of Fallot. Pediatric cardiothoracic surgeon Frank Hanley, MD, has developed a surgical technique called unifocalization that allows him to repair the defect in a single, long operation – which is safer than the alternative of putting babies and children through several open-heart surgeries. Many families come long distances so their children can receive the lifesaving surgery.

Although the Heart Center team is glad to be able to offer state-of-the-art treatment for kids who already have heart defects, they would be even happier to know how to prevent such defects from happening in the first place. Genetics plays into some heart defects, but in most cases, the cause is a mystery.

So this new study, though relatively small with 277 subjects, gives a clue that the Stanford team is eager to follow with other investigations:

“I’m excited by this research because it opens up a lot of questions about how physiologic processes in the mother may be related to congenital heart disease,” Priest said. “Most of the time we don’t have any idea what causes a baby’s heart defect. I aim to change that.”

The study’s senior author, Gary Shaw, DrPH, professor of pediatrics in neonatal and developmental medicine, added, “There are several other kinds of structural birth defects, in addition to heart defects, that have been linked with overt diabetes. This new work will motivate us to ask if underlying associations with moderately increased glucose levels may be similarly implicated in risks of some of these other birth defects.”

I also chatted with pediatric cardiologist and Heart Center director Stephen Roth, MD, who pointed out a practical advantage of the new finding that hadn’t occurred to me: We already know how to address elevated blood sugar with strategies such as dietary change, exercise and medications. If today’s discovery is replicated in larger studies, it wouldn’t be hard to translate it into action.

“It’s always wonderful to discover new information about the cause of a disease or class of diseases,” Roth told me. “And it’s particularly encouraging when we have the possibility of modifying the cause with existing therapies to reduce the likelihood that the disease occurs.”

Previously: Patient is “living to live instead of living to survive” thanks to heart repair surgery, Little hearts, big tools and When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn
Photo by emdot

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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