What’s Next for Cardiac Research and Clinical Care?

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The American Heart Association hosted its annual Scientific Sessions in November. This week-long event provided an opportunity for clinicians, basic scientists, and researchers to discuss what’s new and what’s next for cardiac research and clinical care.

Here’s what Massachusetts General Hospital researchers and cardiologists found most interesting from this year’s sessions:

New guidelines for high blood pressure

Previous guidelines had considered blood pressure below 140/90 to be normal. The announcement at AHA that 130/80 is the new 140/90 came as big news to cardiologists. “We struggle on a daily basis with the management of patients with hypertension. So hopefully these guidelines will help us deliver better care recommendations,” said Malissa Wood, MD, Co-Director of the Women’s Heart Health Program.

Focus on personalization of care

Precision medicine, which takes into account individual variability in genes, environment, and lifestyle, has become a new area of focus. The discussions around precision medicine at this year’s AHA provided insight into how personalized care can be applied in the field of cardiac care. “The precision medicine summit gives me a good sense of where the field is and where the field is going over the next few years,” – said Steven Lubitz, MD, MPH, cardiac electrophysiologist at Mass General.

Issue of whether an individual can get too much exercise

There was much discussion around the impact of strenuous exercise on heart health. “Whether something that we know is inherently good for you can be overdone and actually start causing harm – this continues to be both a scientific and clinical topic that many of us are wrestling with,” – said Aaron Baggish, MD, Director of the Cardiovascular Performance Program.

Check out the full video:

Using Zebrafish Models to Study Cardiovascular Disease

Maryline-squareprofile.jpgMaryline Abrial, PhD, is a postdoctoral research fellow in the Burns Lab at the Cardiovascular Research Center at Massachusetts General Hospital. She took part in a science communication internship at the Mass General Research Institute this fall. She wrote this first-person account of her life as a researcher as part of her internship.

Background and Education

I think what drew me to the biological sciences was a passionate high school biology teacher, who was great mentor and advisor over the years of my undergraduate and graduate training.

I have always found biological processes fascinating. The complexity of them can be very challenging, but understanding and deciphering even a small part feels very rewarding when you can impact human diseases.

Since I started my graduate studies in France in University Claude Bernard in Lyon, I have focused on cardiovascular science. During my PhD, I studied myocardial infarction, which is more commonly known as a heart attack.

My work focused on understanding cellular interactions and especially how non-contractile cell types can help to protect the cells in charge of contraction after an injury such as a heart attack.

After my PhD, I decided to pursue my work in the field of cardiovascular sciences in the exciting scientific environment that Boston offers. I joined the laboratory of Dr. Caroline Burns and Dr. Geoffrey Burns in the Cardiovascular Research Center at Massachusetts General Hospital.

The zebrafish as a model organism

The Burns laboratory studies heart development and regeneration in a particular animal model—the zebrafish.

Unlike humans, zebrafish can regenerate new cardiac tissue after an injury such as a heart attack, which makes them a great model to study the cellular and molecular mechanisms involved in cardiac regeneration.

The zebrafish is also a powerful vertebrate model to study cardiovascular developmental biology because of its rapid external development, the large number of eggs that can be obtained and, more importantly, its beating developing heart that can be observed only 24 hours after fertilization of the egg.

While the zebrafish heart, which is comprised of a single ventricle and atria, is a simpler version of the human heart, the mechanisms regulating its development share much in common.

Investigating aortic arch development

After joining the Burns lab, I slowly became familiarized with zebrafish, and all the genetic tools and imaging techniques that make them such an attractive research model.

I worked closely with a senior research fellow who was studying the development of the great arteries of the heart (also named Pharyngeal Arch Arteries, or PAAs) during embryonic development.

In humans, the PAAs start off symetrically, but then undergo intensive remodeling before taking their final asymetrical shape. Impaired remodeling of those PAAs during development can lead to congenital heart diseases such as Tetralogy of Fallot.

This remodeling process is similar throughout vertebrates, and the zebrafish is a great model organism to visualize and study the cellular progenitors that give rise to these specific arteries.

Using the zebrafish to perform small molecule screening, we uncovered a specific signaling pathway that is involved in the differentiation of great arteries’ cellular progenitors. Using genome-editing technologies, we engineered zebrafish lacking the function of two genes that are involved in this pathway.

Surprisingly, we found that those zebrafish embryos presented a phenotype similar to a human disease called Marfan Syndrome (MFS), a genetic disorder that affects the connective tissue.

People affected by MFS present symptoms in different parts of their bodies, but the most severe ones are linked to the cardiovascular system and include widening or aneurysm of the basis of the aorta (aortic root), which is the main artery carrying blood away from the heart.

This aneurysm can cause a dissection or a tear in the vessel, which will weaken it over time and could lead to a life threatening rupture.

We found that our zebrafish models, when engineered to lack the expression of these two genes, rapidly exhibit an impressive aortic aneurysm (in only 5 days) in a location that is anatomically equivalent to where human aortas are susceptible to developing aneurysm in MFS.

We have analyzed these zebrafish aneurysms and found several molecular hallmarks of the human disease, suggesting that the mechanisms by which zebrafish embryos develop aortic aneurysms are similar to those in Marfan patients.

The Marfan Foundation has funded my research for two years beginning in July of 2016. We are using zebrafish models in combination with genetic tools and microscopic imaging to complement ongoing work in the aneurysm field.

Although tremendous progress has been made in the past decade in the aneurysm research, several questions remain unknown regarding the drivers of the disease.

Current preventive medical therapies for Marfan patients are mainly aimed to reduce blood pressure to decrease the risk of life-threatening complications or to undergo cardiac surgery to repair the aortic root. But so far no therapy has been discovered that prevents or reverses the process of aortic dilation itself.

Because zebrafish embryos are so small and readily available, we can screen large collections of small molecules to looks for candidates that will prevent or cure aortic aneurysm in zebrafish.

In the long run, we hope that any small molecule that suppresses zebrafish aneurysm could be therefore tested in other laboratory models and eventually in humans to learn if they will prevent and/or reverse Marfan Syndrome-associated aneurysm.

The zebrafish gives us a tremendous advantage in studying the pathophysiology of cardiovascular diseases. With the progress of genome editing technologies now readily available, this model can be used to study specific cardiovascular diseases and help to further validate and understand the function of candidate genes identified in human cohorts affected by cardiovascular diseases.

Could Strenuous Exercise Be Bad for Your Heart?

marathon running.jpgIf you’ve noticed a trend in runners signing up for half-, full-, or even ultra-marathons, it isn’t just your subconscious guilting you into exercising — the number of recreational endurance exercise participants has in fact increased in recent years, and RunningUSA predicts the number of participants will continue to rise.

Research has already confirmed that moderate-intensity exercise (like walking briskly, water aerobics, or tennis) on a regular basis can improve heart health. But a recent review conducted by Massachusetts General Hospital’s Aaron L Baggish, MD, director of the Corrigan Minehan Heart Center Cardiovascular Performance Program, found that the same may not be applicable for high-intensity, strenuous exercise. His results were recently published in Current Atherosclerosis Reports.

What did the report find?

Baggish found that among endurance athletes, long-term training has been associated with early onset atrial fibrillation (an irregular heartbeat), changes in the size, shape, structure, and function of the heart, and increased coronary artery calcifications which increases risk for heart attacks and heart failure.

Additionally, data suggests that long-term participation in strenuous levels of physical activity may reduce the life-saving benefits associated with moderate-intensity exercise.

What are the implications for clinicians and patients?

The studies reviewed in this report have produced data that is worth a closer look, but Baggish says that it is too early to draw any definitive solutions. Many of the studies had too small of a sample size to provide any generalizable findings.

Based on the data available, there is no definitive evidence to support clinicians advising against high doses of exercise in healthy athletes. Clinicians who care for highly-active patients should monitor for signs of heart conditions and establish an open dialogue with patients and collaborate on decision making regarding exercise plans.

The results also shouldn’t discourage individuals from sticking to a consistent exercise routine. The American Heart Association suggests at least 150 minutes per week of moderate exercise or 75 minutes per week of vigorous exercise (or a combination of moderate and vigorous activity). Visit the AHA’s website to get ideas on exercise activities.

This article has been adapted from a post on Massachusetts General Hospital’s Advances in Motion.

Could Part of Our Genome Predict Future Risk for Heart Disease?

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Research from Saumya Das, MD, PhD, co-director of the Resynchronization and Advanced Cardiac Therapeutics Program at Massachusetts General Hospital, focuses on studying irregular heartbeats (known as arrhythmias) in patients with heart failure, discovering new tests to better identify who is at risk for developing heart failure or arrhythmias, and uncovering new therapies to treat heart failure.

More specifically, Das is looking at a type of RNA called non-coding RNA which comprise a majority of the genome. Das’ research focuses on identifying RNA biomarkers in the blood that may forecast future risk of heart failure or arrhythmias.

A Mass General and Brigham and Women’s research team, led by Das, is currently validating a newly discovered set of RNA markers in over 4,000 patients as a part of a large-scale, NIH-funded study. Das hopes one day, certain RNA markers might translate in the clinic as a test to help stratify patients based on their risk for heart disease.

Learn more about Das’ research in this video from Advances in Motion:

Women’s Heart Health Program Leaders Look Ahead

Cardiovascular disease — including heart attacks, stroke and heart failure — is the number one killer of adults, but more women die of it than men. The Elizabeth Anne and Karen Barlow Corrigan Women’s Heart Health Program was launched in 2007 to focus awareness, treatments and research on the unique issues women face in maintaining heart health. It was established through a gift from Jerry Corrigan and Cathy Minehan. Program co-directors Malissa Wood, MD, and Nandita Scott, MD, discuss what they’ve learned over the past ten years and the challenges ahead.

Nandita Scott, MD and Malissa Wood, MD, co-directors of  the Corrigan Women’s Heart Health Program

Nandita Scott, MD (left), and Malissa Wood, MD, co-directors of the Corrigan Women’s Heart Health Program

What led you to specialize in cardiology?

Dr. Scott: I went into cardiology because it’s one of those fields where you can make a big difference in people’s lives. There are great diagnostic and treatment tools.

Dr. Wood: The biggest fascination for me was the recognition that cardiovascular disease is the number one killer. I trained a decade before Nandita, when new treatments were emerging. I wanted to use my talents to apply those techniques to help patients have better outcomes.

Why is there a need for a heart health program for women?

Dr. Wood: Cardiovascular disease is underdiagnosed in women. To close the big gaps in care, we wanted to pull together people who understand the pathophysiology of the heart of women, which is quite different than a man’s. Women’s hearts and arteries are smaller, for example. Symptoms of a heart attack can be different for a woman. Another difference is that blockages in smaller blood vessels as opposed to larger arteries are more often the cause of chest pain or angina in women. Our program seeks to tailor therapy and research to women.

When in life should women be most concerned about heart health?

Dr. Wood: All through life. We see patients from age 18 to 100.

Dr. Scott: There are dramatic changes in the cardiovascular system during pregnancy, for example. Blood volume increases and the heart is required to work harder. Pregnancy is like a stress test, a window into future heart health. Those who develop preeclampsia [a potentially dangerous condition that causes high blood pressure] have increased risk of future cardiovascular disease. We formed the Pregnancy and Heart Disease Program to address the needs of women with preexisting heart disease and who develop heart disease during pregnancy.

Dr. Wood: Cardiovascular disease is a major cause of death for women after they give birth. Maternal mortality is worse in the United States than other developed countries and we need to address that.

Your program is now the go-to for young women who have a heart attack due to spontaneous coronary artery dissection, or SCAD, a tear in the artery wall that blocks blood flow. What have you learned about it?

Dr. Wood: It used to be considered rare but that’s because it was underdiagnosed. Because so many are referred here, we have a large register of SCAD patients we are studying. Over 90 percent of them are thin, fit and athletic. Mark Lindsay, MD, PhD, looked at genetic differences and found that only 9 percent have a genetic abnormality. We are also finding that the cumulative effects of stress can trigger a SCAD-related heart attack in women, whereas men were more likely to have a heart attack while exercising. Reducing stress in our lives is extremely important for all women.

Women fear breast cancer but isn’t heart disease more likely?

Dr. Scott: One in ten women gets breast cancer and at least one in three women develops some form of cardiovascular disease. In women, it causes more deaths each year than the next two causes combined — cancer and chronic lower respiratory disease.

Besides exercise and a healthy diet, what should women do to maintain heart health?

Dr. Wood: We found some answers to that question in our Happy Heart study at the MGH Revere HealthCare Center. Lifestyle changes reduced blood pressure, weight and cholesterol, all of which change unfavorably after menopause. We found, too, that chronic stress is a significant risk factor for women and that mind-body therapies can reduce risk. Heart disease is preventable.

What challenges does the program face over the next ten years?

Dr. Scott: We would love to have more staff to accommodate all the women who want to be seen. Seven years ago, Maria Vivaldi, MD, joined us and has a thriving practice at the Revere clinic, helping women who often need us the most. Heart disease in women is now getting more attention; however, there are still many unanswered questions that we would like to research further.

This article originally appeared on the Massachusetts General Hospital Giving website.

Surveys Show How Symptoms and Their Impacts Differ Among Adults with a Congenital Heart Defect

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When it comes to treating the symptoms of patients with a congenital heart defect, researchers from Massachusetts General Hospital are finding that a one-size-fits-all approach won’t meet all patients’ needs. The results of their recent survey provide insight into how clinicians can best tailor care for these patients.

What is CHD?

A congenital heart defect (CHD) is a problem with the structure of the heart that is present at birth. The defects can involve the walls and valves of the heart, and the arteries and veins near the heart. They can disrupt the normal flow of blood through the heart — blood flow can slow down, go in the wrong direction or to the wrong place or be blocked completely.

Complications associated with CHD include abnormal heart rhythms (arrhythmias), heart infection, stroke, and heart failure. CHD is the most common type of birth defect, with approximately 40,000 children born with this condition every year in the United States.

With new treatments and increased survivorship, the number of adults with congenital heart disease (ACHD) has grown significantly over the last 20 years. It’s estimated that more than 1.2 million adults in the U.S. are living with ACHD. However, despite this rise in population, there is still little data available about which symptoms most impact patients’ lives and thus are the most important to manage.

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Ami B. Bhatt, MD

To identify symptoms and help ACHD specialists improve care for their patients, researchers including Ami B. Bhatt, MD, director of the Mass General Adult Congenital Heart Disease Program, and Mass General cardiovascular research fellow Ada Stefanescu Schmidt, MD, MSc, surveyed health care providers and patients to identify the most significant symptoms of ACHD. Their results were published in Circulation: Cardiovascular Quality and Outcomes.

Surveying physicians and patients

First, to create a pool of potentially important symptoms to target for treatment, the researchers surveyed six ACHD physicians, who provided a list of 39 symptoms commonly reported by their patients.

Next, the researchers surveyed 124 ACHD patients and asked them to rank the importance and frequency of these 39 symptoms using 5-point Likert scales. The group was also asked to expand the list by contributing additional symptoms.

Lastly, to confirm the results reported by this initial group, 40 additional ACHD patients from Mass General were given the same survey.

The symptoms

Researchers divided responses into seven groups depending on the severity of the patient’s disease. Six symptoms were identified as being the most troublesome, regardless of disease severity:

  • Shortness of breath (windedness, trouble breathing)
  • Feeling different than other people
  • Having to go to the hospital or emergency room
  • Feeling mentally slower than other people
  • Concerns with sexual function
  • Bluish or dusky colored skin

The Mass General confirmatory group revealed similar results to the larger group with only five of the 39 symptoms differing from the initial group. Of note, the Mass General group rated the symptom “Concern about my children having health problems like mine” higher than the initial group.

The Mass General ACHD Program has already incorporated the findings into their ACHD Health and Wellness Program, run out of the MGH West Facility where physicians and nurses work with patients to address their lives in a holistic manner.

The research team plans to expand their investigation in the future with focus groups and cognitive testing.

This article is an adaptation of a post on Mass General’s Advances in Motion.

 

Understanding Why Exercise Works for Just About Everything

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Editor’s note: This article was originally posted on the Partners Innovation blog, and was written by Gregory Lewis, MD, a cardiologist at Massachusetts General Hospital. 

Centuries ago, the Greek physician Hippocrates noted that when the body is “unused and left idle, it becomes liable to disease, defective in growth, and ages quickly.” These observations—made without the benefit of the exhaustive medical research and detailed studies that we have today—are just as valid now as they were then.

Exercise is a natural medicine available to all. Cardiac research has proven that moderate exercise improves the circulation and metabolism, which reduces the chance of heart attack. Regular exercise also lowers both heart rate and blood pressure, improves the cholesterol profile and helps to prevent the development of life-threatening plaque within the heart’s arteries.

Of course, exercise alone—even if one were to walk more than 100 miles a week—does not grant immunity from life-threatening events such as heart attack and stroke. It can, however, greatly reduce the chances of sudden-death: An exercise study conducted by researchers from the state universities of North Carolina and Washington found that sedentary individuals who devote fewer than 20 minutes a week to vigorous exercise have a 56 times greater risk of dying during their normal activities than do those who exercise for more than 20 minutes daily.

The findings from this study suggest that Americans need to move a lot more: It’s now estimated that 70 percent of Americans are overweight or obese, and approximately 50 percent of adults don’t get enough exercise. Sedentary lifestyle has been directly linked to upwards of 200,000 deaths annually due to coronary artery disease, diabetes, and colon cancer. Some experts now believe that not exercising regularly does as much harm to the body as smoking a pack of cigarettes each day.

Exercising several times a week can be a big step toward improving cardiovascular endurance, muscular strength, muscular endurance, and flexibility—the four basic elements of physical fitness. While each of these elements is essential to overall health, cardiovascular endurance—the ability of the heart, lungs, and circulatory system to do their job—is the most important.

Cardiovascular endurance is built up through exercises or fitness activities that cause the body to deliver increased amounts of oxygen to the exercising muscles. To achieve this, activities must utilize the large muscle groups (such as those in the legs) and, most important, the exercise must be sustained for at least 20 minutes. Importantly, health benefits can be derived from even low-level exercise activities such as walking, hence the “no pain, no gain” paradigm is not the case.

Although fitness has been shown to be among the most potent predictors of future cardiovascular disease, it is one of the only major risk factors that is not routinely assessed by physicians.

Boston researchers are now investigating if specific tests of exercise capacity—and the presence or absence of dozens of molecules in the bloodstream, called metabolites—can be used to identify patients who may benefit from early treatment to prevent cardiovascular disease. The research will also examine how lifestyle, genetic variations, inherited family traits and measurements of heart structure and function match with changes in metabolism during exercise.

This study represents a paradigm shift away from focusing on only resting measurements and a small number of physiologic measurements during exercise in evaluating risk of cardiovascular disease. Instead, the scientists will study breath-by-breath measurements of oxygen uptake as well as a broad array of circulating metabolites during exercise in order to understand metabolic responses to exercise in the population and the ability of exercise response patterns to detect and prevent future cardiovascular disease.

Based on this research, it’s expected within a few years that simple exercise testing equipment will be used in doctors’ offices to assess heart health with a 7-minute test.

For more information about Dr. Lewis’ research, please contact Partners HealthCare Innovation by clicking here.

A Link Between Flu and Heart Attacks? Mass General Cardiologist Weighs In

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New research has found yet another reason to avoid catching the flu this season- it could increase your risk of a heart attack if you’re over the age of 35.

A recent study from investigators at the Institute for Clinical Evaluative Sciences and Public Health Ontario in Canada have found that you’re six times more likely to have a heart attack during the week after being diagnosed with the flu, compared to the year before or after the infection.

However, your chances of having a heart attack when you have the flu depends on your baseline risk. Most of the people who had a heart attack in this study were over the age of 65, and a lot of them had risk factors for heart disease, such as high blood pressure, high cholesterol or diabetes.

Malissa Wood, MD, Co-Director of the Corrigan Women’s Heart Health Program at Massachusetts General Hospital, says that these results confirm the connection between cardiovascular events, such as a heart attack, and respiratory infections like the flu.

“The flu is like a stress test for the heart,” says Wood in this NBC Boston news clip.

Of course, the best way to reduce your risk of flu-related health complications is to avoid getting the flu in the first place. Learn about preventative steps that you can take.

Research Your Resolution: Consider Heart Health Before Going Gluten-Free

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Andrew Chan, MD
Andrew Chan, MD, MPH

Andrew Chan, MD, MPH, Stuart and Suzanne Steele MGH Research Scholar and Chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, recently released the results of a study investigating the widespread perception that a gluten-free diet (for reasons other than gluten allergy) can be beneficial to your heart health.


There is intense interest in the potential health benefits of going “gluten-free” even if one does not have a true allergy to gluten as we see in individuals with celiac disease.

For example, some diet books have recommended a gluten-free diet for longevity and heart health. However, there are surprisingly little data to support this recommendation.

In a large study which tracked the dietary habits of more than  100,000 men and women over the last several decades, we did not find any evidence that a low gluten diet was associated with a lower risk of heart disease.

In fact, a low gluten diet tended to be deficient in foods with whole grains that are actually associated with better heart health.

In some situations, pursuing a low gluten diet could actually be harmful. The lesson here is that the most healthful diets still appear to contain a balance of foods rather than being overly restrictive.


Research Your Resolution

Do you have goals for improving your health in the New Year? This month, investigators from the Mass General Research Institute are discussing the science behind some common New Year’s resolutions, and offering tips and advice based on their research into exercise, diet, healthy aging, heart health, and much more.

Massachusetts General Hospital is home to the largest hospital-based research program in the United States, a community of more than 10,000 people working across 30 departments, centers and institutes. The Mass General Research Institute works to support, guide and promote these research initiatives.

Research Your Resolution: Reduce Your Risk of A Heart Attack

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Do you have goals for improving your health in the New Year? This month, investigators from the Mass General Research Institute are discussing the science behind some common New Year’s resolutions, and offering tips and advice based on their research into exercise, diet, healthy aging, heart health, and much more.


Sekar Kathiresan, MD
Sekar Kathiresan, MD

Sek Kathiresan, MD, is Director of the Center for Genomic Medicine at Massachusetts General Hospital and an Ofer and Shelly Nimerovsky MGH Research Scholar. He studies human genetics to understand the root causes of heart attacks and develop new strategies for preventative cardiac care. To learn more about his research, please visit his lab website.

A family history of heart attacks does not necessarily mean you are destined to suffer one as well.

By studying genetic data from 55,000 individuals who are enrolled in four long-term research studies, we found that following a healthy lifestyle—defined as not smoking, exercising once a week, eating healthy and maintaining a body mass index of less than 30—can reduce your chances of having a heart attack by close to 50 percent.

The basic message of our study is that DNA is not destiny. Many individuals—both physicians and members of the general public—have looked on genetic risk as unavoidable, but for heart attack that does not appear to be the case.