JACC Heart Failure Editor's Update, February 2020
February 2020 JACC: Heart Failure—Mini-Focus Issue: Congenital Heart Disease
We have made great strides in the treatment of advanced heart failure in adult congenital heart disease patients, but challenges remain, as outlined in this State-of-the-Art review. Heart transplantation and mechanical circulatory support are the only effective treatment options for adults with congenital heart disease and complex lesions, but outcomes vary based on factors related to the underlying anomaly and disease of the patient, and the characteristics of the transplant center. Jonathan Menachem et al discuss the use of advanced heart failure therapies in this population and strategies to improve chances for success.
Advanced Heart Failure in Adults With Congenital Heart Disease
Jonathan N. Menachem, JoAnn Lindenfeld, et al.
Dead Letter Office Feature: Exercise capacity declines with age and decreased exercise capacity is strongly associated with cardiovascular disease, particularly heart failure. Better understanding of the mechanisms behind this decline may help inform future treatment and prevention strategies. Ambarish Pandey and colleagues looked at the mechanisms underlying the age-related decline in maximal exercise oxygen uptake (peak VO2) in healthy adults in a cross-sectional, prospective study conducted between 1982 and 1989, and they examined the association of age with invasive hemodynamic cardiovascular parameters.
Healthy Aging and Cardiovascular Function: Invasive Hemodynamics During Rest and Exercise in 104 Healthy Volunteers
Ambarish Pandey, Dalane W. Kitzman, et al.
Does the impact of each of the AHA’s “Life’s Simple 7” modifiable risk factors vary by race and sex? Read this analysis of data from the Southern Community Cohort Study. Danielle Kubicki et al examined the risk of incident heart failure associated with those seven modifiable risk factors at the individual and population levels, overall and stratified by race and sex, to help guide clinical and public health strategies to reduce the incidence of heart failure in a resource-limited setting.
Race and Sex Differences in Modifiable Risk Factors and Incident Heart Failure
Danielle M. Kubicki, Deepak K. Gupta, et al.
Concurrent tricuspid valve repair (TVr) to reduce the risk of right heart failure following LVAD implantation has shown mixed results. Is this due to the durability of the repair? Yaron Barac and colleagues evaluated the durability of concurrent TVr in patients undergoing durable LVAD implantation to examine the incidence and association of TVr failure with the development of late right heart failure.
Durability and Efficacy of Tricuspid Valve Repair in Patients Undergoing Left Ventricular Assist Device Implantation
Yaron D. Barac, Carmelo A. Milano, et al.
Heart Failure Hall of Fame—Getting to Know the Pioneers Who Inspire Us
Our Heart Failure Hall of Fame series brings information about leaders in the field of heart failure beyond their publications and extensive work. This month we feature Marc Pfeffer, MD, PhD. Dr. Pfeffer is the Dzau Professor of Medicine at Harvard Medical School, and Senior Physician in the Cardiovascular Division at the Brigham and Women’s Hospital in Boston. He has received Distinguished Scientist awards from both ACC and AHA, the HFSA Lifetime Achievement Award, and the Gold Medal of the European Society of Cardiology.
What first made you interested in a career in heart failure?
I became fascinated by the heart in college, while doing an experiment with a turtle heart in biology lab, during which we exposed its beating heart and could see the heart respond to changes in temperature and measure force. But even more interesting than the turtle’s heart was my lab partner, Janice, who later became my wife.
From a small college in Rockford Illinois, Jan and I married, and went on to the University of Oklahoma, where we had the incredibly good fortune to meet Dr. Edward Frohlich, a renowned expert in hypertension. I went to graduate school while Janice worked as a technician in his lab, and I was Frohlich’s first graduate student. Then it was Janice’s turn for graduate school, and she was his second PhD graduate student. Dr. Frohlich was my mentor for over 50 years and I mourn his recent passing.
In Dr. Frohlich’s lab, we became interested in the natural development of hypertrophy in rats with genetic hypertension. The ventricle in those rats failed in the long term and this was shown to be preventable if hypertension was treated. I gave a talk on this subject at an AHA meeting and, following that session, a man came up to me and said that our results were not consistent with his findings of papillary muscles from animals with pressure overload hypertrophy. His name badge read Eugene Braunwald.
Professor Braunwald invited us to Boston to talk with him more and, in 1976, Janice and I, and our rats, moved to what was then the Peter Bent Brigham hospital. This has been my home institution ever since.
Through her work in the animal lab, Janice discovered the concept of progressive ventricular remodeling following experimental myocardial infarction. Having previously shown that an ACE inhibitor could regress hypertrophy in genetically hypertensive rats, she hypothesized that, similarly, rats treated with captopril following a myocardial infarction would have less time-dependent ventricular enlargement, which proved to be correct. She allowed me to do a follow-up study, which confirmed that survival was prolonged in the infarct model by ACE inhibitor therapy. My role in that study was to check the rats each night to see which were still alive.
Janice’s work formed the basis of my first clinical trial, which was a relatively small proof-of-concept study evaluating whether ventricular enlargement occurred post-MI in humans and whether ACE inhibitor therapy would attenuate this process. With that information and under Dr. Braunwald’s leadership, and with many incredible colleagues, we conducted a multi-center clinical trial, Survival And Ventricular Enlargement (SAVE), which enrolled 2,231 patients and demonstrated improved prognosis in patients treated with an ACE inhibitor. That trial launched my career as a clinical trialist.
Which of your many accomplishments are you most proud of?
I will list instead the things I am most grateful for.
- I have been enormously fortunate throughout my life. I have had excellent mentors and I work with an outstanding group of colleagues focused on improving outcomes for patients with heart disease.
- I am also grateful to be involved in clinical trials. What a great way to meet colleagues, make new friends, and contribute to advancing patient care.
- My first wife, Janice, was an accomplished cardiac physiologist and scientist. Modifying adverse LV remodeling, a concept introduced by Janice, has become a surrogate target for drug discovery in translational research. As one of many testaments to her accomplishments, following her death in 2000, Ed Frohlich included a tribute to her in his journal Hypertension, and ran her photo on the cover. We had two wonderful children, now adults, and I am very proud of their accomplishments.
- I remarried 13 years ago to Judge Marianne (Mimi) Bowler. A wonderful accomplished woman who loves life, is active, dynamic, and a real fashionista. My friends see a major change in my clothing choices pre- and post- my marriage to Her Honor.
Who inspires you, in your career or otherwise?
I had the good fortune and privilege to work with and learn from two extraordinary scientists and clinicians, Dr. Edward Frohlich and Dr. Eugene Braunwald. Their passion for learning and discovering new and more effective ways to treat patients was infectious and positively inspirational.
What is your favorite, or last book you read?
I love historical novels and always learn something about the times by reading them, but a book I read a while ago, The Poisonwood Bible by Barbara Kingsolver, keeps coming back to my mind. It is about a missionary who takes his family to the Congo. His three daughters lived the very same experience, but each of them perceived it in a different way and each tells a different story. This is just what we see so frequently in daily life: smart well-intentioned people we respect sometimes see the same experiences and events so differently than we do.
3 Things People May Not Know About Me
- After 13 years of marriage I am still on my honeymoon
- I have recently taken up golf and have become a fanatic—but I am terrible at it, due in part, I like to think, to the Boston climate and limited number of good days to get out and play
- The hospital is my gym—with no membership fee. I deliberately take the stairs multiple times a day and find every excuse to walk.
Learn More about Dr. Pfeffer
Marc Pfeffer, MD, PhD, is the Dzau Professor of Medicine at Harvard Medical School, and Senior Physician in the Cardiovascular Division at the Brigham and Women’s Hospital in Boston. A noted researcher, Dr. Pfeffer--along with his late wife, Dr. Janice Pfeffer, and Dr. Eugene Braunwald--is credited with introducing the concept that angiotensin-converting enzyme inhibitors (ACEIs) could attenuate adverse ventricular remodelling following myocardial infarction and that this use would result in a prolongation of survival and other clinical benefits. Since this initial discovery, he has had a principal role in several practice-changing clinical outcome trials.
Dr. Pfeffer is considered a team builder and takes pride in academic advancement of trainees and junior faculty collaborating on the trials. He is known for his fairness in data sharing and assisting others in developing meaningful scholarly works from study databases. He sets high standards for relationships with the sponsors whether industry or NHLBI.
Dr. Pfeffer serves on the Data Safety Monitoring Boards of major international trials. An internationally recognized expert in the field of cardiology, he was recognized by Science Watch as having the most “Hot Papers” (highly cited) in all of clinical medicine. Dr. Pfeffer was listed as one of the highly influential biomedical researchers of 1996-2011 in the European Journal of Clinical Investigation. He is the recipient of the William Harvey Award of the American Society of Hypertension, the Okamoto Award from Japan’s Vascular Disease Research Foundation, the American Heart Association Clinical Research Prize and the James B. Herrick Award, the Distinguished Scientist Awards from both the American Heart Association and the American College of Cardiology, the Lifetime Achievement Award from both the Heart Failure Society of America and the Heart Failure Association of the European Congress of Cardiology, and the Gold Medal Award from the European Society of Cardiology in 2018. Dr. Pfeffer has honorary doctoral degrees from Sahlgrenska Academy and the University of Gothenburg, Sweden, and from the University of Glasgow, Scotland.