Neurohormonal control of heart failure
ABSTRACT
For nearly three decades, starting in the early 1970s, the cardiology research laboratories at the University of Minnesota served as the focal point for the discovery and implementation of much of the information we now apply to the management of heart failure. Director Jay Cohn, building on his expertise in hypertension and hemodynamics, led many creative and committed investigators in the exploration of the mechanisms responsible for increased sensitivity to afterload in heart failure. The neurohormonal hypothesis of heart failure led to the development of several pharmacologic tools, such as angiotensin-converting enzyme inhibitors, β-adrenergic blockers, and, later, angiotensin-receptor blockers. By the late 1990s, it was understood that neurohormonal antagonists could prevent the progression of left ventricular remodeling and favorably influence the natural history of heart failure. Neurohormonal blockers are now considered standard therapy. Issues remain to be addressed, including early identification and treatment of patients at risk.
THE LATER YEARS
By 1997, the face of heart failure had changed. New treatments were effective, but there were new challenges to face. I moved that year to the Cleveland Clinic, where I spent 11 enjoyable and productive years. I returned to Minnesota in 2008 to help build a new cardiovascular division.
It is gratifying to look back and see what has become of the “neurohormonal hypothesis.” Today, nearly all major medical centers have heart failure programs, and certification in advanced heart failure/heart transplantation is a reality. Training programs in advanced heart failure and heart transplant are common. The Heart Failure Society of America sprang up in the early 1990s, dedicated to patients with heart failure. Jay Cohn founded the Journal of Cardiac Failure, which flourished under his leadership. Neurohormonal blockers are now considered standard, conventional therapy and are widely used throughout the world.
CONCLUSIONS
Still, there is much work to do. An increasing number of devices are being developed, largely for patients with more advanced heart failure, but attention is also being directed to prevention of heart failure. Identification and possible treatment of patients at risk for the development of heart failure, and identification of those who already have some early structural and functional perturbation without advanced symptoms, are critically important. Since event rates are so low in these patients, we need to create new strategies for studying interventions. In the long term, the best treatment for nearly any condition is early diagnosis and perhaps early treatment with a goal of prevention.
One consequence of our progress over the years may be that heart failure now primarily affects a more elderly group—patients who often have many associated comorbidities. The consequences include more frequent readmissions, large numbers of patients with intractable signs and symptoms, and the emergence of difficult end-of-life decisions. If we could truly prevent heart failure rather than forestall its emergence to a later point in life, perhaps we could do more good.
For me, the study of neurohormonal mechanisms in the setting of heart failure was the centerpiece of my early career. Jay Cohn had asked several of us early in our laboratory experience to choose a neurohormonal system and learn about it in great depth and detail. My assignment was the SNS. Since then, I have never tired of learning about its control mechanisms, how it achieves circulatory homeostasis, how its excess quantities can be directly toxic to the heart, and the variety of pharmacologic ways that we can control it. I am indeed fortunate to have been part of this amazing study group.
