Cardiovascular Medicine

While many patients may think “doctor knows best” when choosing between different medical procedures, a new study from the California HealthCare Foundation found that some of these decisions may be driven more by local physician preferences rather than clinical evidence.

In some California counties, the local rates of elective procedures are dramatically higher than neighboring areas. For example, a man newly diagnosed with prostate cancer who lives in Tracy, Calif., is 479 percent more likely to undergo internal radiation, i.e., brachytherapy, than the state average. (Click on the map above for rates in other counties.)

To make this data more useful to medical consumers, the study authors published an online interactive map that allows Californians to quickly determine if their region performs elective procedures at disproportionately higher rates than the rest of the state.

“We’re hoping these maps can push along conversations about how to improve health-care delivery,” said Laurence Baker, PhD, a consultant on this study and a professor of health research and policy at Stanford. “One thing that is often important is better communication between patients and doctors, particularly in cases where patients can have different preferences. Getting this information out there might help some conversations happen that could lead to better treatment decisions and health outcomes.”

This new version of the procedure map adds breast cancer, prostate cancer, and spine procedure rates and expanded data to include Medicare patients and younger populations enrolled in commercial plans, Medicaid patients, and the uninsured.

Previously: Heart bypass or angioplasty? There’s an app for that, New breast cancer finding suggests limiting surgery and Ask Stanford Med: Answers to your questions on prostate cancer and the latest research

A short survey that asks patients to assess their walking ability could be helpful in predicting a person’s risk of cardiovascular disease, as well as mortality risks from any cause. That’s according to a Stanford study recently published online in the journal Circulation.

The Walking Impairment Questionnaire, also known as the WIQ, is currently used to predict risks of peripheral artery disease, a narrowing of the arteries that causes limited circulation to the limbs. The authors of this new study wanted to see if the WIQ, which can be filled out by patients while waiting for their doctor appointments, might be helpful in predicting other health risks.

“A 70-year-old patient’s ability to walk six minutes is a great predictor of cardiovascular risks,” said Kevin Nead, a Stanford medical student and the first author of the study. “But most people are seen in 15-minute doctor visits. They’re not going to be doing a walking test.” Perhaps, he reasoned, a subjective test like this 17-question survey could be used instead.

Nead and his colleagues, who examined questionnaire results from more than 1,700 patients, found that the use of the WIQ alone successfully predicted cardiovascular outcomes. In addition, when the survey was used in conjunction with other common clinical tests such as blood pressure measurements and blood tests, it significantly improved the ability to predict mortality not just from cardiovascular disease but from any cause.

“In an era of increasing expense for medical costs, this work suggests that the WIQ, an extremely simple and economical tool, may significantly improve our ability to prognosticate risk,” Nead told me.

Photo by timparkinson

Tiny, bendable biosensors hold the promise of allowing health-care providers to track patients’ vital signs without them having to be tethered to bulky machines. But the difficulty of squeezing sophisticated circuitry onto surfaces no wider than a postage stamp makes designing such devices especially tricky.

To overcome this challenge, Zhenan Bao, PhD, a professor of chemical engineering at Stanford, and colleagues combined layers of flexible materials into pressure sensors to create a small skin-like heart monitor that can be attached to the wrist with a regular-sized adhesive bandage. A Stanford news release offers more details about the device and its potential uses in health care:

When the sensor is placed on someone’s wrist using an adhesive bandage, the sensor can measure that person’s pulse wave as it reverberates through the body.

The device is so sensitive that it can detect more than just the two peaks of a pulse wave. When engineers looked at the wave drawn by their device, they noticed small bumps in the tail of the pulse wave invisible to conventional sensors. Bao said she believes these fluctuations could potentially be used for more detailed diagnostics in the future.

Doctors already use similar, albeit much bulkier, sensors to keep track of a patient’s heart health during surgery or when taking a new medication. But in the future Bao’s device could help keep track of another vital sign.

“In theory, this kind of sensor can be used to measure blood pressure,” said [Gregor Schwartz, a post-doctoral fellow and a physicist for the project]. “Once you have it calibrated, you can use the signal of your pulse to calculate your blood pressure.”

This non-invasive method of monitoring heart health could replace devices inserted directly into an artery, called intravascular catheters. These catheters create a high risk of infection, making them impractical for newborns and high-risk patients. Thus, an external monitor like Bao’s could provide doctors a safer way to gather information about the heart, especially during infant surgeries.

The team’s work is described in paper published today in Nature Communications.

Previously: Touch-sensitive, self-healing synthetic skin could yield smarter prosthetics, Beetle wing design inspires ultra-sensitive electronic skin, Stanford researchers develop transparent, stretchable skin-like sensor and Stretchable solar cells could power electronic ‘super skin’
Photo in featured entry box by L.A. Cicero

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.”