TAG: "Heart"

Researchers discover how high blood pressure damages the heart


Biological trigger found that makes heart beat stronger in response to higher blood pressure.

Ye Chen-Izu, UC Davis

The heart’s ability to adjust its contraction strength in response to increases in blood pressure can, when the condition becomes excessive, lead to arrhythmias and other serious heart conditions.

Now, a multidisciplinary research team at UC Davis has found a key biological trigger — a protein known as nitric oxide synthase, or NOS — that makes the heart beat stronger in response to higher blood pressure, along with a way to turn that trigger off when it becomes overactive.

“The heart is a robust pump that can compensate for short-term increases in blood pressure due to changes in physical and emotional conditions — like exercise or joy,” said study senior author Ye Chen-Izu, assistant professor of pharmacology and biomedical engineering at UC Davis. “But there is a darker side to that compensating system that could lead to life-threatening heart diseases. Our work opens up new avenues for preventing that outcome.”

Chen-Izu pulled together an interdisciplinary team of biophysicists, chemists, engineers, physiologists and cardiologists for a study of the biological system that controls contractility of the heart under mechanical stress such as that caused by high blood pressure. They put heart muscle cells from mice into a “cell-in-gel” system that simulates mechanical stress on cells. The system, which was developed by Chen-Izu and Kit Lam, chair of the UC Davis Department of Biochemistry and Molecular Medicine, is transparent, allowing changes at the molecular level to be observed as they occur in living cells through high-power microscopes.

A series of experiments showed that as mechanical stress increases, the release of calcium increases and strengthens heart contractions so it can pump harder against higher blood pressure. They identified NOS as the molecule that initially senses mechanical stress and creates nitric oxide, which activates ryanodine receptors that increase the calcium release.

The researchers also discovered that an isoform of NOS — neuronal nitric oxide synthase, or nNOS — was responsible for spontaneous calcium sparks that occurred when cells were supposed to rest, likely due to the buildup of nitric oxide from ongoing mechanical stress.

“Under conditions of heavy, persistent mechanical load, the heart’s fine-tuned calcium control system becomes unstable, causing irregular heartbeats,” said Chen-Izu, whose research focuses on the biomechanics and bioelectricity of heart disease. “This could explain why high blood pressure can increase arrhythmias, which may lead to sudden cardiac death, heart failure and stroke.”

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Injectable hydrogel for treating heart attacks licensed to startup


UC San Diego project will be among those presented at Research Expo on April 17.

UC San Diego bioengineer Karen Christman’s new injectable hydrogel, which is designed to repair damaged cardiac tissue following a heart attack, has been licensed to San Diego-based startup Ventrix Inc, which is planning the first human clinical trials of the technology. Christman is a co-founder of Ventrix.

In a 2013 study published in Science Translational Medicine, Christman reported the semi-solid, porous gel encourages cells to repopulate areas of damaged cardiac tissue and to preserve heart function. The hydrogel forms a scaffold to repair the tissue and increases cardiac muscle.

You can learn more about this technology at Research Expo on April 17, where Christman is one of six faculty speakers at the UC San Diego Jacobs School of Engineering event. Wang, an M.D./Ph.D. student in bioengineering, will present a poster explaining her research on how the hydrogel works to rebuild tissue in damaged hearts.

More than 200 forward-looking research projects will be presented. The annual event features cutting-edge research posters by engineering graduate students and their faculty advisors; ten-minute faculty talks; and a networking reception with faculty, students, industry partners and alumni.

Research Expo will be held on Thursday, April 17, from 2-6p.m. Register today.

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Early cardiac risks linked to worse cognitive function in middle age


Blood pressure, glucose, cholesterol in 18- to 30-year-olds predicts decline.

Kristine Yaffe, UC San Francisco

Young adults with such cardiac risk factors as high blood pressure and elevated glucose levels have significantly worse cognitive function in middle age, according to a new study by dementia researchers at UC San Francisco.

The findings bolster the view that diseases like Alzheimer’s develop over an individual’s lifespan and may be set in motion early in life. And they offer hope that young adults may be able to lower their risk of developing dementia through diet and exercise, or even by taking medications.

“These cardiovascular risk factors are all quite modifiable,” said senior author Kristine Yaffe, M.D., a professor in the departments of psychiatry, neurology, and epidemiology and niostatistics at UCSF, who holds the Roy and Marie Scola Endowed Chair in Psychiatry.

“We already know that reducing these risk factors in midlife can decrease the risk of dementia in old age,” continued Yaffe, who is also chief of geriatric psychiatry and director of the Memory Disorders Clinic at the San Francisco VA Medical Center. “If it turns out that the damage begins before middle age, we may need to expand our focus and work on reducing heart disease risks in earlier stages of life.”

The study, published today (March 31) in Circulation, examines data from more than 3,300 18- to 30-year-olds in the Coronary Artery Risk Development in Young Adults (CARDIA) study, which began enrolling thousands of participants nationwide in 1985 to understand how heart disease develops in black and white adults.

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Unique use of heart-lung machine saves heart attack victim


ECMO is normally reserved for transplant patients, but quick-thinking UCLA staff used it to help James Manzi.

James Manzi and his wife, Barbara

James Manzi is lucky to be alive. When the 79-year-old Brentwood resident arrived at  Ronald Reagan UCLA Medical Center’s emergency room in full cardiac arrest, the medical team tried everything to stabilize him, including shocking his heart 29 times with a defibrillator in an attempt to restore a normal rhythm.

Often, patients whose heart attacks are as severe as Manzi’s don’t survive. Only one out of every 10 people who suffer cardiac arrest outside the hospital lives through the ordeal.

As the team worked, UCLA emergency medicine physician Dr. Eric Savitsky monitored Manzi’s diminishing response to their resuscitative efforts using a combination of bedside ultrasound of the heart and clinical indicators. This led to an emergency request for a rarely used but potentially lifesaving technology known as extracorporeal membrane oxygenation, or ECMO.

ECMO involves the use of a sophisticated pump that takes over the functions of the heart and lungs, essentially breathing for the patient by pumping oxygenated blood to vital organs so the lungs can rest. This helps reduce stress on the heart. The device is traditionally used to support adults in cardiac failure waiting for a heart transplant and to help protect the delicate respiratory systems of infants born prematurely.

Fortunately, it worked in Manzi’s case, too. His heart stabilized, allowing the cardiac team to transport him to the cardiac catheterization lab, where he underwent coronary angioplasty on an artery that was completely blocked. Following the procedure, doctors placed a stent in the artery to keep it open; blood flow was completely restored.

While Manzi’s heart function recovered enough that ECMO was removed three days after his heart attack, he had also suffered anoxic brain injury as a result of his brain not getting enough oxygen during the heart attack — a common occurrence after cardiac arrest. After five weeks in the hospital’s intensive care unit, he was transferred to UCLA’s neuro-rehabilation unit, where he completed his rehabilitation, making a nearly 100 percent recovery.

At a recent follow-up visit, UCLA cardiologist Dr. William Suh, who performed the cardiac procedures during Manzi’s heart attack, confirmed that the patient is doing remarkably well. Manzi is very grateful to the cardiac and emergency teams that went the extra mile to save his life. He’s now looking forward to his 80th birthday on April 6.

“I’ve always enjoyed my life and now appreciate it even more,” said the father of five, who also has six grandchildren. “Just being alive is wonderful.”

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Heart scans only useful in prescribing statins under certain conditions


UCSF researchers create statistical model to predict whether it makes sense to do the scan.

Mark Pletcher, UC San Francisco

As long as inexpensive statins, which lower cholesterol, are readily available and patients don’t mind taking them, it doesn’t make sense to do a heart scan to measure how much plaque has built up in a patient’s coronary arteries before prescribing the pills, according to a new study by researchers at UC San Francisco.

The researchers created a statistical model to predict whether or not it made sense to do the scan, using data from the Multi-Ethnic Study of Atherosclerosis and other sources. They modeled the effects of statin treatment in 10,000 55-year-old women with high cholesterol and a 10-year risk of coronary heart disease of 7.5 percent. The model predicted that giving statins to all of them would prevent 32 heart attacks, cause 70 cases of statin-induced muscle disease and add 1,108 years to their cumulative life expectancy.

Then, they looked at how a coronary artery calcium test, or CAC test, could be used to target statin therapy only to those women who the CAC test showed were at heightened risk of coronary heart disease. They found that this strategy would save money on statin costs and expose fewer women to side effects from statins but would not prevent as many heart attacks. Moreover, the test itself exposes the women to a small risk of radiation-induced cancer and costs about $200 to $400 per scan.

The researchers concluded that as long as the price of a statin remained low – 13 cents a pill – and did not reduce quality of life for patients, it was not cost-effective to perform a CAC test to target the drug therapy only toward those at increased risk of coronary heart disease. But if the price of the pill were more expensive – $1 or more – or if taking them reduced patients’ quality of life, then it did make sense to use the CAC test.

The result is somewhat surprising, given all the evidence that has accumulated over the last decade that the test strongly predicts heart attacks, said the lead author, Mark Pletcher, M.D., M.P.H., an associate professor of epidemiology and biostatistics, and medicine, at UCSF. The study was published online March 11 in Circulation: Cardiovascular Quality Outcomes.

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Young mother delivers baby, develops heart disease


UC San Diego Sulpizio Cardiovascular Center among first in region to implant cardiac device.

Amanda and her husband, Nathan, doting on their beautiful daughter, Kassidy, minutes after her arrival.

Three weeks after delivering her first child, Amanda began to suffer from extreme fatigue, headaches, a tight chest and stomach pain. An initial diagnosis of pneumonia changed for the worse: Amanda was experiencing heart failure. The 28-year-old’s life was at risk. She was quickly transferred to UC San Diego Sulpizio Cardiovascular Center (SCVC) where a multidisciplinary team implanted a novel cardiac device under her skin, leaving the heart untouched, to prevent sudden cardiac arrest.

“When Amanda first arrived at SCVC, she was in critical condition. It became clear within 24 hours that she needed emergency surgery or she would not survive,” said Eric Adler, M.D., director of cardiac transplant and mechanical circulatory support at UC San Diego Health System.

The new mother was diagnosed with peripartum cardiomyopathy, a rare disorder in which a woman develops heart disease within the final month of pregnancy or within five months after delivery. Adler adds that one in 2,000 women suffers from the condition, the cause is not exactly known and it can be hard to correctly diagnosis.

“I knew I had to fight for my daughter,” said Amanda. “I am not a quitter and always strive for success. I wasn’t going to let heart failure beat me.”

A left ventricular assist device (LVAD) – a mechanical heart of sorts that helps pump oxygen-rich blood throughout the body – was first implanted in Amanda.

“The patient’s heart was failing. She was in a dire situation and needed the LVAD device immediately implanted to support her heart function and restore blood circulation,” said Victor Pretorius, M.B.Ch.B., cardiothoracic surgeon at UC San Diego Health System, who implanted the LVAD in Amanda.

Amanda was also a candidate for the new Boston Scientific Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) System. The device is used for the treatment of patients at risk for sudden cardiac arrest. To date, more than 3,000 devices have been implanted in patients around the world.

The S-ICD System monitors cardiac activity and shocks the heart when it goes into a dangerous rhythm, a function not performed by the LVAD. The S-ICD does not use traditional wires, called “leads,” threaded to the heart through blood vessels. Rather, the device is implanted just under the skin near the breastbone, and heart patients who require an ICD may be candidates.

“Leads in standard ICDs have been known to fracture or disconnect at times. The S-ICD has fewer long-term complications, an easier removal process and puts the patient at less risk for infection,” said Ulrika Birgersdotter-Green, M.D., director of pacemaker and ICD services at UC San Diego Health System, who implanted the device in Amanda. “It is an advancement in defibrillation technology that is simple to implant and can be life-saving.”

Amanda was the first patient at UC San Diego Health System to receive the S-ICD. The procedure took about an hour, and she was able to walk around the next day. As she continues to heal, she will be closely monitored to see if her heart function improves. If not, she will be placed on a heart transplant list.

“As part of the region’s only academic hospital, we are dedicated to using a team approach to treat high risk patients, who five to ten years ago, may not have survived,” said Adler.

Amanda is now sharing her story to raise awareness about heart disease.

“Knowledge and early detection for heart disease, especially peripartum cardiomyopathy, are key. I hope my story helps others to understand the warning signs and the technology available for treatment,” said Amanda. “The first time I was able to hold my daughter after the procedure, I became very emotional after the journey I had just been through. Because of the team at SCVC, I am able to embrace my family every day.”

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Know the risks: Kawasaki disease and pregnant women


UC San Diego researchers say risks are manageable, provided doctors recognize them.

Jane Burns, UC San Diego

In the first study of its type, researchers at the UC San Diego School of Medicine have looked at the health threat to pregnant women with a history of Kawasaki disease (KD), concluding that the risks are low with informed management and care.

The findings are published in today’s (March 6) online edition of the British Journal of Obstetrics and Gynaecology.

KD is a childhood condition affecting the coronary arteries. It is the most common cause of acquired heart disease in children. First recognized in Japan following World War II, KD diagnoses are rising among children in Asia, the United States and Western Europe. Predictive models estimate that by 2020 one in every 1,600 American adults will be affected by KD.

“A growing number of women with a history of KD are reaching child-bearing age, but there is little information available to guide their obstetrical care,” said study author Jane C. Burns, M.D., professor and director of the Kawasaki Disease Research Center at UC San Diego and Rady Children’s Hospital-San Diego. “By and large, KD is virtually unknown among working obstetricians.”

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Study evaluates infliximab’s role in treating Kawasaki disease


Antibody treatment helps children with dangerous heart disorder.

Adriana Tremoulet, UC San Diego

Kawasaki disease (KD) is a severe childhood disease that many parents, even some doctors, mistake for an inconsequential viral infection. If not diagnosed or treated in time, it can lead to irreversible heart damage.

Signs of KD include prolonged fever associated with rash, red eyes, mouth, lips and tongue, and swollen hands and feet with peeling skin. The disease causes damage to the coronary arteries in a quarter of untreated children and may lead to serious heart problems in early adulthood. There is no diagnostic test for Kawasaki disease, and current treatment fails to prevent coronary artery damage in at least 1 in 10 to 20 children and death in 1 in 1,000 children.

Between 10 and 20 percent of patients with KD experience fever relapse following the standard therapy with a single infusion of intravenous immunoglobulin (IVIG) and aspirin. It is known that IVIG resistance increases the risk of heart damage, most commonly a ballooning of the coronary arteries called aneurysms. These children require additional therapy to interrupt the inflammatory process that can lead to damage of the coronary arteries.

A study led by physicians at the UC San Diego School of Medicine and Rady Children’s Hospital-San Diego looked at intensification of initial therapy for all children with KD in order to prevent IVIG-resistance and associated coronary artery abnormalities by assessing the addition of the medication infliximab to current standard therapy. The results of their study will be published in today’s (Feb. 24) online issue of the medical journal Lancet.

Tumor necrosis factor α (TNFα) is a molecule made by the body that plays a role in the development of inflammation in KD; therefore, treatment with a TNFα antagonist is a logical therapeutic intervention, according to the researchers. Early experience with infliximab – a monoclonal antibody that binds TNFα– showed promising results. A Phase 1 trial in children with KD and persistent fever following standard therapy found no infusion reactions or serious adverse events, and subsequent studies suggested that infliximab led to faster resolution of fever and fewer days of hospitalization than a second IVIG infusion.

The UC San Diego researchers conducted a trial of 196 subjects at two centers – Rady Children’s Hospital-San Diego, a research affiliate of UC San Diego School of Medicine, and Nationwide Children’s Hospital in Columbus, Ohio – to assess whether infliximab could reduce IVIG treatment resistance.

“While the addition of infliximab to primary treatment in acute KD did not reduce treatment resistance, it was safe and well-tolerated, achieved a greater reduction in the size of the left coronary artery, and reduced the number of days of fever and laboratory markers of inflammation,” said the study’s first author, Adriana H. Tremoulet, M.D., of the UC San Diego Department of Pediatrics and the UC San Diego/Rady Children’s Hospital-San Diego Kawasaki Disease Research Center.  “We conclude that use of infliximab is safe in infants and children and that early treatment could help children with Kawasaki disease with high levels of inflammation or early signs of coronary artery damage.”

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New molecular ‘cocktail’ transforms skin cells into beating heart cells


Study represents important step toward therapies that regenerate heart muscle.

Sheng Ding

The power of regenerative medicine appears to have turned science fiction into scientific reality — by allowing scientists to transform skin cells into cells that closely resemble beating heart cells. However, the methods required are complex, and the transformation is often incomplete. But now, scientists at the UC San Francisco-affiliated Gladstone Institutes have devised a new method that allows for the more efficient — and, importantly, more complete — reprogramming of skin cells into cells that are virtually indistinguishable from heart muscle cells.

These findings, based on animal models and described in the latest issue of Cell Reports, offer newfound optimism in the hunt for a way to regenerate muscle lost in a heart attack.

Heart disease is the world’s leading cause of death, but recent advances in science and medicine have improved the chances of surviving a heart attack. In the United States alone, nearly 1 million people have survived an attack, but are living with heart failure — a chronic condition in which the heart, having lost muscle during the attack, does not beat at full capacity. So, scientists have begun to look toward cellular reprogramming as a way to regenerate this damaged heart muscle.

The reprogramming of skin cells into heart cells, an approach pioneered by Gladstone Investigator, Deepak Srivastava, M.D., has required the insertion of several genetic factors to spur the reprogramming process. However, scientists have recognized potential problems with scaling this gene-based method into successful therapies. So some experts, including Gladstone senior investigator Sheng Ding, Ph.D., have taken a somewhat different approach.

“Scientists have previously shown that the insertion of between three and seven genetic factors can result in a skin cell being directly reprogrammed into a beating heart cell,” explained Ding, the paper’s senior author and a professor of pharmaceutical chemistry at UCSF. “But in my lab, we set out to see if we could perform a similar transformation by eliminating — or at least reducing — the reliance on this type of genetic manipulation.”

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Blood test serves as ‘crystal ball’ for heart transplant patients


Test can predict potential rejection-related problems in the future.

Mario Deng, UCLA

A new UCLA-led study shows that a blood test commonly used to determine whether heart transplant recipients are rejecting their new organ can also predict potential rejection-related problems in the future.

Reporting in the online edition of the peer-reviewed journal Transplantation, researchers demonstrate how the AlloMap test, which uses a blood sample to measure changes in the expression of roughly a dozen genes, can be used over a period of time to assess the risk of dysfunction or rejection of a transplanted heart — months before such an event may occur.

“For the first time, we can use genomic testing over multiple patient visits to go beyond intuition to understand not just how patients are doing now but how they are likely to be a few months from now,” said Dr. Mario Deng, medical director of UCLA’s Integrated Advanced Heart Failure–Mechanical Support–Heart Transplant Program and the study’s principal investigator. “It’s another step toward personalized medicine.”

The discovery that transplant recipients’ white blood cells contain this prognostic information on rejection, independent of how their transplanted heart may be functioning currently, could potentially improve care and outcomes, the researchers said. The findings represent a significant step in the movement toward using genomic-based testing to predict future clinical events and bolster the importance of similar tests being developed for recipients of other organs.

In the U.S., approximately 2,000 patients receive lifesaving heart transplants each year, and monitoring their immune systems for signs of rejection is a critical part of follow-up care. Until recently, however, the only way to diagnose rejection was through a heart-muscle biopsy, a painful and potentially risky procedure in which a heart catheter is inserted through a vein in the neck.

That changed with the development of the AlloMap gene-expression profiling test, which received clearance from the Food and Drug Administration in 2008. The test is now routinely used by a majority of U.S. heart transplant centers to monitor low-risk patients during follow-up care, resulting in a substantial reduction in the number of biopsies.

AlloMap, which is based on research Deng led in conjunction with more than a dozen of the largest U.S. heart transplant centers and the Brisbane–based biotech company XDx, measures the expression levels of 11 genes from a patient’s blood sample, each of which is known to be associated with rejection risk.

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Genetic cue found for sudden cardiac death syndrome


UC Irvine discovery could lead to improved early detection and prevention strategies.

Geoffrey Abbott, UC Irvine

UC Irvine researchers have found a specific genetic flaw that is connected to sudden death due to heart arrhythmia – a leading cause of mortality for adults around the world.

While a number of genes have been linked with arrhythmias, UC Irvine’s Geoffrey Abbott and his colleagues discovered that the functional impairment of a gene called KCNE2 underlies a multisystem syndrome that affects both heart rhythm and blood flow and can activate chemical triggers that can cause sudden cardiac death.

“With these findings, we can now explore improved early detection and prevention strategies for people who are at higher risk of sudden cardiac death, such as those with diabetes,” said Abbott, a professor of pharmacology and physiology & biophysics in the UC Irvine School of Medicine.

Study results appear in the February issue of Circulation: Cardiovascular Genetics, a publication of the American Heart Association.

Distinct from a heart attack, in which the heart continues to beat but blood flow is blocked, sudden cardiac death occurs when the heart ceases to beat because of the uncontrolled twitching of muscle fibers in its ventricles. Without defibrillation within minutes, this type of event is fatal.

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Women’s group recognizes UC medical centers’ commitment to heart care


Best hospitals for heart care include four UC medical centers.

Four University of California medical centers were among 290 hospitals nationally to be recognized by WomenCertified as a Best Hospitals for Patient Experience in Heart Care. WomenCertified is a consumer advocate that seeks to assist women’s health care choices by identifying hospitals with records of excellence in the treatment of heart attacks and heart disease.

The selection of best hospitals for heart care included UC Davis Medical Center, UC Irvine Medical Center, Ronald Reagan UCLA Medical Center and UC San Diego Medical Center – Hillcrest.

“Everyone on our cardiovascular team, including physicians, nurses, technicians and therapists, is committed to providing its patients with the highest quality cardiac care available,” said Dr. Pranav Patel, chief of the UC Irvine Health Division of Cardiology.

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