Broken Hearts

When Kelly Axsom, MD, meets a new patient, she always makes time for a tough talk. “I tell them, ‘My goal is to help you live the best life you can, as long as you can.’” And then she asks what brings them joy, what makes their life complete.

The ensuing conversations can be emotionally intense, says Dr. Axsom, especially because as a cardiologist at Columbia’s Center for Advanced Cardiac Care, it is often her job to share bad news. “We’re breaking the news to patients about really scary things—heart replacement, end of life,” says Dr. Axsom. “Understanding who they are can help us do that with grace.”

Consider, for example, the story of a patient hospitalized 11 times in the year leading up to her first encounter with Dr. Axsom. “When someone has a hospitalization for heart failure, their median life expectancy starts to tick down,” Dr. Axsom says. The stats are ominous—heart failure is a syndrome that affects an estimated 6.5 million Americans and is a leading cause of hospitalization, with 1 million admissions per year in the United States. Median survival for those hospitalized is 2.5 years; for those hospitalized more than three times for heart failure, life expectancy drops to less than one year. “It’s not well understood by the public or even physicians that it’s that big of a deal,” says Dr. Axsom. “This is a morbid condition.”

Already in her 70s, the new patient meeting with Dr. Axsom was ineligible for a heart transplant; palliative care with a well-calibrated combination of diuretics and other medications was her only treatment option. At regular checkups, pressures in the woman’s heart and lungs looked good, but the frequent hospitalizations suggested more was going on. Dr. Axsom urged her patient to participate in remote monitoring.

In remote monitoring, a wireless unit installed in the distal pulmonary artery continuously measures pulmonary artery pressure and heart rate and transmits the data to a patient’s health care provider. “We can watch a patient’s trends, see if pressures are going up, and give more diuretic to prevent a patient from coming into the hospital,” says Dr. Axsom. Such early interventions avert the spiral of water retention and shortness of breath that will further diminish cardiovascular function and typically trigger a hospitalization. Nationwide, remote monitoring devices have been credited with a 63% reduction in hospitalization. At Columbia, where Dr. Axsom leads an effort to offer remote monitoring to all patients with heart failure, hospitalization has been reduced by 86%.

"Physicians may be too quick to label someone frail, their disease more advanced, their bodies unable to tolerate therapies when those patients are women."

In this particular case, monitoring furnished the clue Dr. Axsom needed for a plan to stabilize her patient at home. “Every Saturday, her pressures would shoot up,” says Dr. Axsom. A few follow-up questions revealed that the woman hosted her extended family every weekend for a celebration featuring a lavish array of food, drink, and festivity, not all of it strictly in keeping with a cardiologist’s recommendations. Using the remote monitoring data, Dr. Axsom modified her patient’s diuretics to buffer the effect of those cherished gatherings and preserve the matriarch’s connections with those she loves most. “We’ve been monitoring her for two years now—long enough for her to see her daughter married,” says Dr. Axsom. “She’s doing pretty well, considering the state she was in when we met her.”

Leading Cause of Death in Women

Nationwide, one in four women dies of cardiovascular disease, making it the No. 1 cause of mortality in women. While those same statistics apply equally to men, particulars of risk factors, diagnosis, and treatment differ radically between the sexes. Women are often older when diagnosed, with a greater number of comorbidities; pregnancy, childbirth, and menopause affect both risk of disease and treatment options when symptoms develop; and social roles—as mothers, as caregivers—alter the attention paid to heart health in the decades when prevention has its greatest effect.

The types of cardiovascular disease women develop are also different. The left-ventricle failures more common to women remain harder to diagnose than right-sided systolic failure, with fewer treatment options available. Symptoms differ, too. While chest pain remains the cardinal sign of a heart attack, “atypical” symptoms—such as nausea and fatigue—that are experienced more often by women do not always register with patients or health care professionals. That more than triples the average time to diagnosis and treatment. Further compounding the issue, women historically have been underrepresented in clinical trials for cardiovascular treatments and interventions and many recent studies have failed to parse outcomes by sex of participants.

At VP&S, women cardiologists are working to turn the tide by calling attention to the disparities, educating both patients and health care colleagues about risk and prevention, conducting novel research to reveal differences in disease course, and refining treatment for the types of heart disease more common among their female patients. “I’m proud of the strides we’ve made at Columbia to reverse disparities and enhance the cardiovascular care we deliver to all women patients,” says Allan Schwartz, MD, chief of Columbia’s cardiology division. “This year, women account for 12 of the 25 fellows in the division. Columbia’s capacity to positively impact women’s health will only multiply as our fellows graduate and go out into the world.”

When editors of the journal Heart Failure Clinics decided to devote the January 2019 issue to women, Dr. Axsom was one of three VP&S cardiologists they invited to review disparities in advanced heart failure management and outcomes. Senior author Maryjane Farr, MD, is the medical director of the adult heart transplant program at Columbia. First author Marlena Habal, MD, completed two fellowships at Columbia, one in advanced heart failure and transplant and the second in translational immunology, before joining the faculty.

Disparities in Heart Transplantation

Men receive at least 70% of heart transplants in the United States. Causes for the disparity are complex, says Dr. Farr, and many remain poorly understood. The later age and different phenotype of heart failure in older women (more diastolic rather than systolic heart failure), along with more frailty and other co-morbidities, make heart transplantation for older women less common and more problematic.

Even when women are listed for heart transplant, they are more likely to die before a donor heart is available. Here, too, the causes are many. Smaller rib cages mean women wait longer for donor organs that fit within their chest cavities. In a March 2019 report for the Journal of the American College of Cardiology, Dr. Farr and colleagues found profound disparities when they examined the use of mechanical circulatory support devices, often used to buy time for people with advanced heart failure who have been added to the transplant waitlist. Women comprised just 20% of the patients who received a continuous-flow left ventricular assist device over a 10-year period in the United States. They also found that women who did receive an assist device had lower chances of heart transplantation and increased risk of waitlist mortality. In the two years following implantation, women had almost double the risk of being removed from the list because of worsening clinical status.

Previous exposure to another person’s immune system, known as human leukocyte antigen (HLA) sensitivity, increases the difficulty of selecting a donor organ and is also associated with more complicated post-transplant immunosuppression and greater risk of rejection. Within her general practice as a transplant cardiologist and immunologist, Dr. Habal sees more men than women. As a transplant immunologist using immune-modulating protocols to increase the odds of a successful transplant for patients with HLA sensitivity, however, she sees more women—primarily mothers who were exposed to the immune systems of their newborns during delivery.

The Role of Bias in Cardiac Care

Beyond the factors that can be tied directly to biological differences between the sexes, both Dr. Farr and Dr. Habal worry that provider bias plays an underrecognized role in the management of heart failure. “Women can be sicker when they present,” says Dr. Habal, “but we also have to consider perception among clinicians.” In their January 2019 article for Heart Failure Clinics, Drs. Habal, Axsom, and Farr reported that although women and men are affected by advanced heart failure in equal numbers, women have been consistently underrepresented in clinical trials. Further, despite multiple studies that showed no sex-based difference in medication tolerance or response, physicians seem to use less thorough and less aggressive protocols to treat their female patients. They are also less likely to refer their female patients to advanced heart failure experts and transplant centers. “Physicians may be too quick to label someone frail, their disease more advanced, their bodies unable to tolerate therapies when those patients are women,” says Dr. Habal, noting that no clinical standard exists for the diagnosis of frailty.

To investigate the extent to which transplant teams also fall prey to perception bias, Dr. Farr has partnered with cardiology fellow Ersilia DeFilippis, MD, first author on the Journal of the American College of Cardiology article, to conduct a retrospective review of patient charts. They plan to analyze the rates at which patients referred to Columbia’s transplant team are accepted or rejected as candidates for transplant, with a close eye not only on blood work and other clinical measures, but also on intangibles, such as psychiatric and social work evaluations, availability of supportive caregivers, and the like. “We’re looking at whether, in real time, we are participating in these biases,” says Dr. Farr. “It may be we’re rejecting people because of inadequate caregiver support, or they’re too old or frail, which is a buzzword that comes up a lot more often with women than with men.”

Leaders of the Women’s Heart Health Group, from left: Elsa-Grace Giardina, Sonia Tolani, Natalie Bello, and Jennifer Haythe.

Exploring Differences in How Heart Disease Progresses

Elsa-Grace Giardina, MD, a longtime Columbia cardiologist and pioneer in women’s health, was already an established NIH-funded investigator with a specialty in the clinical pharmacology of arrhythmia when she decided in the early 1980s that more data were needed to understand the ways in which heart disease progresses differently among women and men so they could tailor treatment accordingly. That curiosity was far from universal, a point that came through loud and clear in responses to her first application for NIH funding on the topic. “Why is the proportion of women so high in the study?” queried two of three reviewers. “Everybody knows that heart disease is a disease of men.”

Happily, says Dr. Giardina, a lot has changed in the past four decades. In 1994, she founded Columbia’s Center for Women’s Health in Cardiology. “That was just around the time when the nation was beginning to recognize that there were differences in women’s hearts and men’s hearts,” she recalls. Now known as the Women’s Heart Center and co-directed by Dr. Giardina with Jennifer Haythe, MD, and Sonia Tolani, MD, the center boasts a team of 17 cardiologists with specialties including screening and prevention, coronary artery disease, vascular disease, pregnancy, hormone replacement, and more, all tailored to women’s physiology.

Still, work remains. In a 2012 survey, the American Heart Association found that 44% of women were aware that heart disease is the leading cause of death among women; rates of awareness were lower among Black women and Latinas. Stents, bypass surgery, and statins have led to reductions each year in the number of cardiovascular deaths over the past decade, but rising rates of risk factors, including obesity, diabetes, and hypertension, threaten to erase those gains. “Heart disease as we know it today is really controllable,” says Dr. Giardina. “We’re beginning to understand the risk factors in more detail and identify young women who do not yet know they’re at risk and who could be treated more effectively.”

To help women come to grips with those risk factors and boost adoption of the lifestyle habits that promote heart health, Women’s Heart Center clinicians Sonia Tolani and Natalie Bello, co-directors of a working group on women’s heart disease awareness, created the Love My Heart app. Using a series of 12 questions, the app calculates a user’s personal risk of developing heart disease. “Women have different risk factors than men,” says Dr. Tolani. “Diabetes doubles risk of heart disease for men but triples the risk for women, for example. And complications during pregnancy and early menopause also impact risk.” The working group on women’s heart disease awareness is part of the Columbia Center for the Study of Social Difference, an interdisciplinary research group that fosters ethical and progressive social change by supporting collaborative projects that address gender, race, sexuality, and other forms of inequality.

"A large number of women—about 80% of us—have at least one risk factor for heart disease, but only 16% of us have had a discussion with our health care provider about those risks."

The app invites users to devise a personalized action plan with realistic goals to support healthy weight, healthy diet, exercise, and smoking cessation. Users select goals, such as skipping dessert or getting off the subway a few stops early, then receive prompts throughout the day to log their progress. “A large number of women—about 80% of us—have at least one risk factor for heart disease, but only 16% of us have had a discussion with our health care provider about those risks,” says Dr. Tolani. “We hope the app sparks new conversations among women and with their providers.”

Raising Awareness Among Medical Professionals, Patients

Few women in their 20s, 30s, and 40s will see a cardiologist, says Dr. Giardana, but many receive well-woman or pregnancy-related medical care, creating myriad opportunities for nurse practitioners, physician assistants, and MDs in other fields to screen their female patients and raise awareness. “They are the gatekeepers,” says Dr. Giardina, “and that gives them a tremendous responsibility to contribute to reducing heart disease among women.”

To raise awareness among health care professionals, VP&S hosts “Heart Disease and Women,” an annual continuing medical education program co-sponsored by NewYork-Presbyterian and Weill Cornell. Dr. Haythe, who also directs Columbia’s High-Risk Cardiology Obstetric Service, co-directs the one-day symposium with fellow cardiologists Nisha Jhalani, MD, Dr. Tolani, and Weill Cornell’s Holly Andersen, MD. The symposium, held each February during American Heart Month, features lectures that cover the latest practice guidelines for screening and prevention of cardiovascular disease, gender-specific vascular disease, heart health during pregnancy and menopause, and treatment innovations for valvular heart disease in women. “We focus on the point-of-care contact of ob/gyns and their patients and how cardiovascular risk can be assessed effectively,” says Dr. Haythe.

While some risk factors are immutable—family history, for example, or pre-eclampsia during pregnancy—Dr. Haythe emphasizes that Americans make choices every day that can increase or reduce their risk. Drink water, she urges, instead of soda or sugary fruit juices. If you smoke, suffer insomnia, or feel depressed, ask for help. Take the meds prescribed to control blood pressure and diabetes. And get moving. “I was always drawn to cardiology because I felt there was a lot you could do for people, we had a lot of treatment options, and people could feel a lot better,” she says. “I actually enjoy giving encouragement to patients, telling them all the stuff they can do. Seeing them follow through and feel so much better is really awesome.”

Right: Cardiologist Marwah Abdalla.

Sleep has emerged as another risk factor for women. Brooke Aggarwal, EdD, a cardiovascular behavioral medicine specialist, studies sleep and cardiometabolic risk across the lifespan in a diverse population of women. In February, the Journal of the American Heart Association published Dr. Aggarwal’s analysis of the sleep and eating habits of an ethnically diverse group of 495 women, ages 20 to 76. “Women are particularly prone to sleep disturbances across the lifespan because they often shoulder the responsibilities of caring for children and family and, later, because of menopausal hormones,” says Dr. Aggarwal.

Similar to findings of previous studies of sleep and diet, the study found that women with worse overall sleep quality consumed more of the added sugars associated with obesity and diabetes. “Given that poor diet and overeating may lead to obesity, a well-established risk factor for heart disease, future studies should test whether therapies that improve sleep quality can promote cardiometabolic health in women,” says Dr. Aggarwal.

 To reach the general public, the Cardiovascular Research Foundation’s Women’s Heart Health Initiative offers free “mini-med schools” with expert lectures on such topics as “Stress and Heart Disease” and “Diabetes and Your Heart.” Dr. Jhalani, a clinical cardiologist with the Center for Interventional Vascular Therapy at NewYork-Presbyterian/Columbia, is also director of the Women’s Heart Health Initiative. “We’re trying to reach people before they experience heart disease and motivate them to prevent it for themselves and their families by sharing what they learn with their loved ones,” says Dr. Jhalani, who notes that among women, diabetes has an outsized effect on heart health, both increasing the risk of having a heart attack at a younger age and leading to poorer outcomes in the aftermath. “Empowering the lay public to talk to their doctors about their risk factors is really important.”

In her own practice, says Dr. Jhalani, she regularly sees women who know something is wrong, but can’t quite put their finger on it—a woman who takes the stairs from the subway every morning and suddenly develops shortness of breath, another with high cholesterol whose daily workouts were growing shorter because she just didn’t feel right. “Luckily, these patients listened to themselves. Even though they’d been to a doctor and been told ‘Don’t worry about it,’ they insisted on a referral,” says Dr. Jhalani. “We cardiologists need to have a keen ear for what seems concerning or different to each individual patient—man or woman—who we see in our practice.”