Think Tank on Congestive Heart Failure in Women

Need for a “Think Tank” on Coronary Disease and Heart Failure:

In the United States, more women than men die within one year of a myocardial infarction (38% vs 25%) according to the AHA Heart Disease and Stroke Statistics for 2006.  Within 6 yrs of a myocardial infarction, more women than men are disabled from heart failure (46% vs 22%) and more women than men are likely to have a recurrent myocardial infarction (35% vs 18%)    Despite this knowledge, gender specific therapy for coronary heart disease is very limited.  There have been a few studies that have described coronary artery disease as a very different syndrome in women when compared to the men.  The WISE trials sponsored by NIH described the presence a lower plaque burden, erosion of plaques, rather than fissure and more symptoms of angina, albeit atypical at times.  The need for expansion of these studies and dissemination of findings cannot be overemphasized.  Coupled to the “Red Heart” campaign of the AHA, the need for further studies specifically designed for women becomes clearly evident.  Unfortunately, less women are referred for cardiac rehabilitation and secondary prevention after an event than men in the same age group and same disease burden.

Heart failure affects 5 million people and more than 50% of these individuals are women.  Currently, no gender specific therapy for women with heart failure exists and too few women have participated in studies to be able to generalize the information to women.  In addition, medications that have been tested in a primarily male population have been “automatically” extended to women.  Retrospective analyses of large databases have sometimes questioned the benefits of certain drugs in the women enrolled in the trials.  Furthermore, women in heart failure trials are often more advanced, more symptomatic and have a greater prevalence of hypertension as an etiology.  Although advances have been made in the heart failure device arena, most trials have also included primarily men.  The size of a female chest cavity may not accommodate a ventricular device with ease.  In fact, pediatric devices may be better suited for women, but the data have not been collected.

After 25 years of heart failure clinical experience including cardiac rehab and dozens of clinical trials, including over 50% women in our 1000 patients in the Heart Failure Clinic at University Hospitals, the need for further gender-specific research looms high in Dr. Piña’s field of vision.  Questions remain as to presentation, coronary disease mortality and medical therapy benefits in the female patients.   Dr, Piña’s interest in pursuing this area has continued to increase after contributing several book chapters related to heart failure, one of which specifically focused on women.  Her realization that more work needs to be done sparked her enthusiasm to plan a Cardiovascular Think Tank to bring together the best minds in heart disease with  government agencies to truly share information and decide on a specific roadmap for acquiring important new information specifically targeting women.  At the end, the women patients that we serve at the Heart Failure Center at University Hospitals will only benefit from this union of minds.

The initial Think Tank on Congestive Heart Failure in Women convened on February 16, 2006 in Bethesda Maryland in response to public health concerns resulting from disparities in management of cardiovascular diseases and related outcomes in women.  The purpose of the workshop was to provide an interdisciplinary forum to discuss promising and novel approaches to management of cardiac disease and its risk factors and to identify promising new directions in related research. The ultimate goal of The Think Tank is to create multi-center prospective studies for women with cardiovascular diseases. This was the first of several meetings, organized by Drs. Eileen Hsich and Ileana Piña (Case Western Reserve University) supported by the Office of Women’s Health (US Public Health Service) and the CASE National Heart Failure Training Program with participation by National Heart Lung Blood Institute (NHLBI), together with the Food and Drug Administration (FDA, ODE), each within the Department of Health and Human Services (DHHS). 

For this initial meeting there were two primary tasks. The first was to identify gender gaps in knowledge regarding treatment and pathophysiology for two cardiovascular diseases in women: 1) heart failure and 2) coronary artery disease.  The task was to review the data available by having most participants give 5-10 minute presentations on a particular topic related to one of the areas. The second goal was to discuss potential areas of research.  The workshop provided a unique opportunity to gather experts to chart a new course for future gender-based studies.

I.  Overview of opportunities to save lives

Conference participants unanimously agreed that existing and new therapies and technologies can save thousands of lives currently lost due to major cardiovascular disorders. They recommended two broad strategies to pursue aggressively:   First, study existing evidence-based therapies known to be effective in reducing cardiovascular morbidity and mortality in men to determine their effectiveness in women.   Second, identify specific areas of need for future applied research focused on women.

The group acknowledged that earlier and better risk factor identification, rapid diagnosis, and early control of ischemia will lead to improved survival.  There was optimism that new strategies and therapeutic interventions will save the lives of patients who fall outside the "typical window" of current interventions. They applauded earlier emphasis on focal or regional ischemia, including myocardial infarction and stroke, and urged recognition of the need to address ischemia without significant epicardial obstructive coronary disease (CAD). They discussed possible sources for new therapeutic interventions such as the frontiers of molecular medicine, basic cardiovascular sciences, pharmacology, and epidemiology. They also talked about new diagnostic techniques and technological advances targeting women such as device miniaturization.  They agreed diverse disciplines, including the basic sciences, clinical sciences and biotechnology should be integrated to improve understanding of women’s physiology and the translation of new insights into life saving medical practices.

To advance the science and technology focused on saving lives they recommended specific actions for follow up in future meetings:

A. Evaluate established clinical databases to facilitate understanding of gender specific risk factors and outcomes and interventions.

B.  Expand translational and applied focused research through new research initiatives, including collaborative and integrated research projects uniting basic and applied scientists.

C. Improve methodologies for the following three areas

1. Early identification of clinically relevant atherosclerosis
2. Acquisition of physiologic data including initial data and ongoing data
3. Devise technologies to guide and enhance initial and ongoing interventions.

The goal of the second meeting which will be held on July 13, 2006, at the FDA in Rockville, Maryland will be to further brainstorm about possible research projects in the area of coronary artery disease and heart failure.  Research projects will be prioritized and individuals will be assigned particular projects.  Ultimately, participants will work together to help each other prepare the best grants possible and to collaborate for multi-center studies in the area of coronary artery disease and heart failure.  The group will brainstorm further to review the priorities discussed at the first meeting and to discuss the topics for possible research.  With the goal of advancing science and technology to save lives at high risk for coronary artery disease and heart failure, they will select initial topics for research from the list of possibilities below.

A. Evaluate established clinical databases to facilitate understanding of gender specific risk factors and outcomes and interventions. 

1. Identify research priorities for funding, contingent on demonstration of sufficient numbers of women included in trials, including: coronary disease and myocardial infarction, heart failure (preserved and impaired systolic function). 
2. Utilize these studies to expand professional and lay education which may lead to funding.

B. Expand translational and applied focused research through new research initiatives, including collaborative and integrated research projects uniting basic and applied scientists.

1. The focus should be on pathophysiologic mechanisms and options for optimizing and/or restoring the cardiovascular status to normalcy.

 

2. New initiatives should expose differences among pre-menopausal and postmenopausal populations and the differences between primary prevention and ischemic states.

 

3. Novel clinical science approaches and molecular genetic approaches to gender-based medicine should improve therapeutic interventions. 

 

4. Subjects of special interest include: (a) microvascular ischemia, (b) metabolic syndrome, (c) peripartum cardiomyopathy and development of therapies for peripartum injury; and (d) the role of vasculature in settings of diabetes.

D. Improve methodologies for the following three areas

1. Early identification of clinically relevant atherosclerosis
2. Acquisition of physiologic data including initial data and ongoing data
3. Devise technologies to guide and enhance initial and ongoing interventions

Currently there are 27 participants who have agreed to participate at the second meeting, including representatives from NHLBI and FDA.