Cardiovascular Medicine

When I recently learned that my cholesterol was a bit high, I was told that a regular exercise routine and a couple of oatmeal breakfasts per week should do the trick to bring the numbers back to a normal range. But for Brenda Gundell, a genetic disease called Familial Hypercholesterolemia, or FH, means that simple lifestyle changes won’t make for a quick fix.

FH affects cholesterol processing from birth, and while the condition is common - affecting more than 600,000 people in the U.S. - it is diagnosed in less than 10 percent of those who have it. Gundell was only 15 when she first heard about FH; her father, just 39 at the time, had such extreme levels of total cholesterol that they led to a fatal heart attack. Fortunately for Gundell, while the disease can be destructive, it is, in fact, treatable. And, with the help of FH specialists at Stanford’s Preventive Cardiology Clinic, Gundell has kept her cholesterol in check for the last 17 years and is looking forward to a long life.

Grundell’s story is detailed in the Stanford Hospital video above.

A new online tool can help seniors with advanced heart disease decide between two possible medical interventions - Coronary Artery Bypass Graft surgery or Percutaneous Coronary Intervention, a.k.a. angioplasty.

To use the tool, seniors enter in their age, gender, diabetes status, tobacco use and heart disease history. The tool then calculates a predicted five-year survival rate, based on outcomes of similar patients who underwent these procedures. These predictions are derived from data extracted from the medical records of more than 100,000 Medicare patients, and analyzed using a model recently published in a study led by Mark Hlatky, MD, professor of health research and policy and of cardiovascular medicine at Stanford.

I had the pleasure of working with the amazing team of health researchers and programmers who developed this medical decision tool in a little under a month. For me, it was a sneak preview into the future of personalized medicine, where a person can review surgical outcomes of real-world patients with similar health histories, to reach an informed decision on a treatment plan with their physician.

“Studies usually focus on the results for the average patient, and not on how much the results vary among individuals. This model is a step towards personalizing treatment recommendations, based on each individual’s unique characteristics,” Hlatky told me. “The other exciting thing about this new methodology is that with relative ease, it can be applied to other medical conditions such as cancer and stroke.”

Hlatky will present his model and findings at the Institute of Medicine workshop “Observational Studies in a Learning Environment,” which can be viewed via a webcast on April 24-25.

Previously: Is stenting or surgery better for diabetics? New study provides answer, New test for heart disease associated with higher rates of procedures, increased spending and To stent or not to stent: not always an easy answer
Illustration by Dawn Johnson/iStock

Congenital heart defects, abnormalities in the heart that occur during fetal development, are the most common type of birth defect, with the Centers for Disease Control and Prevention estimating that one million American adults are currently living with one. Some types of congenital heart defects can be mild and require no medical treatment, while others such as transposition of the great arteries were once fatal and today require lifelong cardiac care.

In transposition of the great arteries (TGA), the aorta and pulmonary artery, two major vessels that carry blood away from the heart are transposed. This causes blood from the lungs to flow back into the lungs and blood from the body to flow back into the body without getting the proper amount of oxygen. Brooke Stone was diagnosed with the condition as a newborn and, like many infants, underwent a complex surgery to correct her blood flow. While Stone’s congenital heart defect was successfully repaired in infancy, the surgical fix meant she had to sit out of gym class as a child, and it produced some deadly complications for her later in life.

But thanks to a second life-saving surgery performed last September at Lucile Packard Children’s Hospital, Stone can now enjoy a full life. In today’s Inside Stanford Medicine, my colleague offers a closer look at Stone’s story and how Frank Hanley, MD, director of the Children’s Heart Center at Packard Children’s, is pioneering a new approach to improve surgical repairs for TGA:

Instead of backing away from the [conventional approach, which had poor patient outcomes], he looked closer to understand its limitations. “The idea that everyone who needed the procedure could just be slam-dunked into the arterial switch was wrong,” he said. “We focused on setting rigid criteria for accepting people into the program, and setting up a five-point report card after left-ventricle training to ensure that we were selecting appropriate patients who would have good outcomes.”

Today, Hanley may be the only surgeon in the United States doing the procedure. A careful process of multiyear monitoring, patient selection and rigorous evaluation is key to his successful approach. Over the past 15 years, as the criteria for selection and the procedure have evolved, the survival rate for Hanley’s patients has grown to exceed 90 percent. So far, Hanley has managed 36 patients with a failing Mustard/Senning procedures, and estimates that thousands more in the United States may still need lifesaving intervention of some kind.

The story goes on to explain how Packard Children’s is working in tandem with the multidisciplinary Adult Congenital Heart Program at Stanford to better provide monitoring and care of survivors of congenital heart surgery.

Previously: Advancing heart surgery for the most fragile babies and Little hearts, big tools
Photo by Chris Conroy

This last winter has been a tough one for my small rural community. Every time I turned around, more people were sniffling and sneezing, coughing and feverish. We’ve all been just as likely to compare doctors’ recommendations as our children’s report cards, and more than one of my friends walked away from the physician with a prescription for a Z-pack: a five-day regimen of an antibiotic called Zithromax that’s effective in treating many common infections.

Last week, however, the Food and Drug Administration strengthened their warning about Zithromax: Mounting evidence has shown that the drug can be dangerous for people with certain preexisting heart conditions, or those who may be taking other drugs that affect the heart’s rhythm.

How could such a common medication carry such risks? It’s simple, explain Stanford scientists. The current methods of testing a prospective new drug’s heart safety profile depend primarily on the use of non-heart cells that are genetically modified to mimic some aspects of real ones. But they’re no substitute for the real thing. Unfortunately, the “real thing” is hard to get. After all, we’re not all lining up for heart biopsies so scientists can have a steady supply of material on which to test each drug.

Today cardiologist Joseph Wu, MD, PhD, medical student Andrew Lee, and postdocs Ping Liang, PhD, and Feng Lan, PhD, published some really exciting new work in the journal Circulation (subscription required) that presents an alternative. In short, the researchers collected painless skin samples from patients with one of three inherited cardiac conditions, as well as from healthy family members. They then used induced pluripotent stem, or iPS, cell technology to convert the skin cells in the laboratory into functioning heart cells that reflected each patient’s specific heart aliment. Finally, they tested the response of the cells to specific medications - some of which have been shown to be relatively safe for the heart and another that had been withdrawn from the market due to unexpected cardiotoxicity. As Lee explained in our release:

It’s clear that individual patients will respond uniquely to specific drugs. If you have a hereditary disease or a problem with your ion channels, you’re going to respond differently than members of the general population. Even companies relying on genetically normal human embryonic-stem-cell-derived cardiac cells won’t be able to see all these effects. But our ‘clinical trial in a dish’ with patient-specific iPS cells allows us to model this personalized response and identify high-risk groups who should not receive the drug.

The researchers found that the heart cells in the dish responded in much the same way to the medications as did human patients. They anticipate that this type of “clinical trial in a dish” may become a standard method of testing drugs for cardiotoxicity on healthy and diseased hearts. It may also allow researchers and clinicians to test the effect of combinations of drugs while limiting the risk to real patients. Although none of my antibiotic-toting friends have been harmed by Zithromax (and thank goodness, we all seem to be feeling a bit better!), who would argue with better, faster and safer testing of all drugs? According to Wu:

Our hope is that, instead of a physician using a patient as a guinea pig, trying one medication after another until something is found to be effective, this method will one day lead to personalized drug screening to find out exactly which medication is the best for you.

I’m really excited about this research, and in this use for iPS cells in general. We’ll likely be hearing more about this approach; earlier this week Wu, who co-directs the Stanford Cardiovascular Institute, received$1.44 million from the California Institute for Regenerative Medicine to collect tissue samples to create iPS cells from several hundred patients with idiopathic familial dilated cardiomyopathy - that is, members of families with a predisposition to develop enlarged and weakened hearts without an obvious cause.

Previously: Sudden cardiac death has a cellular cause, say Stanford researchers, New leaders in heart medicine at Stanford and Lab-made heart cells mimic common cardiac disease in Stanford study
Photo by kaibara87

Stem-cell therapy for damaged hearts is a brilliant idea whose time has not yet come. To date, human and animal trials - there have been quite a few - in which stem cells were injected into cardiac tissue to treat severe heart attacks or substantial heart failure have mostly produced poor results.

Stanford’s Sam Gambhir, PhD, MD, who heads the medical school’s Department of Radiology, thinks he knows part of the reason why, and he may have found a way around it.

At present, there’s no way to ensure against faulty initial placement, he told me in an interview about his study describing the proposed solution, just published in Science Translational Medicine. “You can use ultrasound to visualize the needle through which you deliver stem cells to the heart. But once those cells leave the needle, you’ve lost track of them.”

In my release about the work, I wrote:

As a result, key questions go unanswered: Did the cells actually get to the heart wall? If they did, did they stay there, or did they diffuse away from the heart? If they got there and remained there, for how long did they stay alive? Did they replicate and develop into heart tissue?

Gammbhir’s lab has figured out a way to “mark” stem cells before infusing them into the heart, rendering them visible to standard ultrasound as they’re squeezed out of the needle. The key was to invent an innovative imaging agent, in the form of nanoparticles whose diameters clustered just below one-third of a micron — less than one-three-thousandth the width of a human hair. The nanoparticles’ main ingredient, silica, shows up on ultrasound. The particles were also doped with the rare-earth element gadolinium, so they can also be observed using MRI.

It turns out that mesenchymal stem cells — a class of cells often used in heart-regeneration research because they can differentiate into beating heart cells and because they can sometimes be harvested directly from the patients themselves, avoiding possible immune-compatibility problems — were happy to gobble up the nanoparticles in a lab dish without losing any of their ability to survive, thrive, and replicate themselves.

When Gambhir and his associates infused these nanoparticle-loaded stem cells into the hearts of healthy mice, they were indeed able to monitor the cells via ultrasound after they left the needle tip, guide them to the targeted area of the heart wall, and still get a strong MRI signal from the cells two weeks later.

Stem-cell therapy for damaged hearts isn’t going to be cheap anytime soon. (A wild guess of, say, $50,000 per procedure is probably not too far off the mark.) But a one-time delivery, if it worked, could replace a lifetime of constant drug administration. Adding what Gambhir estimates might be another $2,500 a pop for the added imaging capability is likely to be hugely cost-effective, because it could greatly improve the odds of the procedure’s success.

Previously: Nanoparticles home in on human tumors growing in mice’s brains, increase accuracy of surgical removal, Nanomedicine moves ones step closer to reality and Developing a new molecular imaging system and technique for early disease detection
Photo by miguelb

Heart disease is the primary cause of death for the more than 20 million people in the United States with chronic kidney disease (CKD). For kidney patients who have secondary diagnoses of coronary artery disease or diabetes, which puts them at particularly high risk of heart attack or stroke, the cholesterol-lowering drugs statins are routinely prescribed.

But for the remainder of patients with chronic kidney disease, it’s unclear whether statin treatment is either cost effective or medically prudent. A Stanford study published today in the Journal of the American College of Cardiology sheds some light on the issue.

…At very low prices, generic statins are cost-effective in nearly all patients with chronic kidney disease

“We did a cost-effectiveness analysis weighing the potential benefits in patients with chronic kidney disease and hypertension,” first author Kevin Erickson, MD, a Stanford nephrologist, recently explained to me. “We essentially show that at very low prices, generic statins are cost-effective in nearly all patients with chronic kidney disease, but at average retail prices they are only cost-effective in patients with kidney disease who have higher cardiovascular risk.”

The study also indicates that adverse side effects of these drugs, including muscle-related toxicity, and potential diabetes and memory loss, should be taken into consideration by clinicians when determining treatment options. “While statins reduce absolute [cardiovascular disease] risk in patients with CKD, increased risk of rhabdomyolysis, and competing risks associated with progressive CKD, partly offset these gains,” Erickson and his co-authors cautioned in the paper.

Previously: Wider statin use may be cost-effective way to prevent heart attacks

Research published online yesterday in the New England Journal of Medicine shows a novel anti-clotting drug to be superior at preventing blood clots during coronary stenting procedures compared to the currently used medication.

The study included about 11,000 patients from 153 centers around the world and was led by co-investigators Robert Harrington, MD, chair of the Department of Medicine at Stanford, and Deepak Bhatt, MD, at Harvard. The results of the trial, which were presented at the American College of Cardiology conference in San Francisco yesterday, showed that the drug, called cangrelor, reduced the odds of negative outcomes from stenting procedures such as blood clots, heart attacks and strokes, by 22 percent when compared to the routinely used anti-platelet drug clopidogrel (tradename Plavix).

We need a very potent agent to prevent clotting when we are putting things in the heart artery like wires and stents. We want a fast acting reversible agent, which is why a drug like cangrelor could be useful and why we tested it.

Coronary artery stents are used in the majority of patients who undergo percutaneous coronary intervention (PCI). In the United States, an estimated 600,000 of these procedures are done per year on patients who suffer from coronary artery disease, which causes arteries to become narrowed or blocked.

In our press release, Bhatt comments on why the discovery of a new drug like this is important to patients. He said, “We need a very potent agent to prevent clotting when we are putting things in the heart artery like wires and stents. We want a fast acting reversible agent, which is why a drug like cangrelor could be useful and why we tested it.”

As the leading cause of death among both men and women worldwide, cardiovascular disease is a health concern that’s near and dear to all our hearts. Earlier this month, we asked interventional cardiologist William Fearon, MD, to respond to questions about heart health and cardiovascular research in honor of American Heart Month. Below he answers a selection of questions submitted via our @SUMedicine Twitter feed and the Scope comments section.

As a reminder, these answers are meant to offer medical information, not medical advice. They’re not meant to replace the evaluation and determination of your doctor, who will address your specific medical needs and can make a diagnosis and provide appropriate care.

Heather asks: I’ve experienced infrequent heart palpitations my whole life, mostly when lying down. But lately I’ve been experiencing them daily. At what point do heart palpitations signal a more serious condition?

Palpitations are a very common condition and in most cases benign. When palpitations become bothersome or frequent, most patients will seek medical attention. Vital signs such as low blood pressure or rapid heart rate can be a sign that the palpitations represent a more serious cardiac arrhythmia. Some simple tests such as an electrocardiogram, echocardiogram, blood tests and wearing a cardiac monitor can help to rule out any worrisome arrhythmia. Often changes in lifestyle, such as abstaining from caffeine products and getting more sleep, will relieve palpitations. Occasionally, medications are necessary.

Don Stanathan asks: I was diagnosed with dilated cardiomyopathy and later diagnosed with stage 4 lung cancer. I am stable and going strong, but I have had high blood pressure and high cholesterol for years and have been on medications for both. My question is how high can you allow your overall cholesterol level go before it overrides the cancer issues?

This is a difficult question to answer because it depends on weighing the risk of cancer against the risk of heart disease and balancing these risks with the risk of taking medications to prevent either of the above. One method for determining one’s risk from heart disease is the Framingham Risk Score, which can be accessed from any search engine on the web. After determining your risk of suffering a heart-related issue, you can discuss with your physicians the pros and cons of taking medications to reduce this risk.

Rebecca asks: A recent study shows that individuals with a common genetic variant for a certain type of cholesterol have a significantly (60 percent) greater risk of developing aortic calcifications. How might these findings lead to new therapeutic treatments or prevention options?

The relationship between lipid abnormalities and the development of aortic stenosis has been recognized for many years. This has prompted studies aimed at lowering cholesterol in an attempt to slow the progression of aortic stenosis. Unfortunately, these studies did not show any benefit to this strategy, perhaps because the population of patients studied and the method of lipid lowering used. The recent study to which you are referring found that a genetic variant in the lipoprotein(a) locus results in elevated levels of lipoprotein(a) and the development of aortic valve disease. With this new information, studies can be designed to include patients with this genetic variation and to treat them with medications specifically aimed at reducing lipoprotein(a). Whether this will result in prevention of aortic valve disease remains to be seen.

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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; the latest comes from retired nurse Joan Jahnke.

After 2 ½ years of seeking a definitive diagnosis for my heart disorder, my physician of 14 years told me, “You have been insistent, persistent and consistent each time you presented.” She smiled at me as she said this, and I accepted this compliment as a job well done.

I had been diagnosed with cardiac endothelium dysfunction. I considered the diagnosis a triumph of some sort: Standard tests don’t always identify the disease, and I had gone on quite the journey to identify the source of my problems.

From the beginning, I had stayed focused on my heart symptoms. When various specialists insisted on blaming other organs (gall bladder, uterus, lungs) for my chest pain, I was insistent that they were off target. As a cardiac nurse, I knew that the mounting conflicting test results were confusing, but I felt confident my heart was the issue. After all, I knew myself far better than anyone else could.

Within weeks of my symptom onset, I read an interview with Dr. George Sopko, a cardiologist at the National Institutes of Health, who said, “Women, pay attention to your heart symptoms.” And so, I did that. I began a very succinct journal documenting the timing, duration and quality of chest pain I was experiencing, and I also included what I did to relieve the symptoms. It presented a cause-and-effect pattern with details that supplemented my memory.

I persisted in my search for a definitive diagnosis for my symptoms. My sources were not anecdotal stories from Internet blogs, but instead were scientific papers funded by medical universities and research institutions. I copied medical articles, whose content and format would be most familiar to physicians. I sought out the opinions of medical friends and colleagues, and I approached my research from the perspective of a student - not that of an emotionally distraught woman whose quality of life was rapidly failing.

I remained consistent in my approach. Mindful of how time-consuming difficult diagnoses can be, I came prepared for appointments. I brought with me my ever-present journal, previously prepared questions and medical articles. Many times, my husband would serve as my note-taker, which allowed me to listen closely and concentrate on getting my questions and comments addressed. I offered options for my physicians to consider. I was wrong many times, but never was I rebuffed.

My behaviors culminated in a referral to the Emory Heart Center in Atlanta. By then I was very short of breath, and pain dominated my life. I forwarded my precious journal to the Emory cardiologists, Dr. Jerre Lutz and Dr. Habib Samady, and asked them to read it prior to my appointment. Dr. Lutz knew by page four what was wrong! And he immediately initiated a medical plan of action, in conjunction with Dr. Samady.

My advice to anyone traveling on the difficult road to a diagnosis is to not become the difficult patient - that is, the patient who doesn’t keep track of tests or medication trials as the medical record grows in size, who doesn’t return for appointments, or who disrupts an office practice and makes accusations that no one is listening to his or her complaints. A squeaky wheel doesn’t always get the first or best attention.

Instead, develop a set of behaviors that make you a participant in your healthcare - not merely its recipient. And be insistent, persistent and consistent in your communication and relationship with your physicians.

Joan Jahnke, a retired R.N. with experience in cardiac nursing, lives in South Carolina. She has written about her heart experiences and been active on the Internet since 2008. In 2012, she appeared on a PBS show to discuss how her heart disorder has changed her life, and the difficulties she had in obtaining a diagnosis.

If you, like me, only get your blood pressure checked during the occasional doctor’s visit, then you may want to read this Stanford BeWell Q&A with Kathy Berra, clinical director of the Stanford Heart Network. In it, Berra describes how monitoring your blood pressure can help prevent heart attack, stroke, heart failure and kidney failure.

As Berra also notes in the piece, “approximately 30% of the American adult population has high blood pressure,” and the “American Heart Association estimates that 90% of all American adults are at risk for elevated blood pressure during their lifetime.” She recommends that people self-monitor, and she goes on to offer advice on how to do so and to explain what the numbers mean:

Both the top and bottom numbers are important to watch. The top number is called systolic blood pressure — the pressure exerted by the heart when it squeezes to pump blood to the rest of the body. The bottom number, diastolic blood pressure, is the pressure in your vascular system (blood vessels) during the phase when the heart is resting. You want to make sure the heart only pumps as hard as it needs to pump to get blood out to your body, and you need to control the pressure exerted against the heart when it is trying to rest. Therefore, both numbers are important. The number that generally guides medication management is the top number, or the systolic blood pressure.

More than half of all heart attacks, strokes and heart failure cases in the United States are caused by high blood pressure, according to data from the National Institutes of Health. This week, Stanford interventional cardiologist William Fearon, MD, is taking questions about cardiovascular research, including advancements in diagnosing, treating and preventing heart disease and stroke, via our @SUMedicine Twitter feed and comments section on Scope.

Previously: Ask Stanford Med: Stanford interventional cardiologist taking questions on heart health and Stanford Hospital & Clinics introduces month-long heart health challenge
Photo by HazPhotos