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Despite the common belief that the massively dilated and dysfunctional hearts of patients with severe end-stage heart failure are irreversibly damaged, recent evidence has shown that the support of these hearts with left ventricular assist devices (LVADs) can lead to normalization of heart structure and improved strength of heart muscle. According to a new study by physician-scientists at NewYork-Presbyterian Hospital, published in Circulation, these observations support the concept that LVADs may someday be used as an integral part of new therapeutic approaches to permanently normalize heart function in some patients, thus obviating what would otherwise be a pressing need for heart transplantation.

Abnormal contraction and relaxation of the failing heart have been linked to alterations in the proteins that regulate release and uptake of calcium within heart muscle cells. The new study also demonstrates that LVAD support reverses abnormal expression of these proteins in failing human hearts, and it relates this change to improved contractile function of heart muscle. The study shows that even severely dysfunctional human hearts retain the molecular capacity for recovery under certain conditions.

Chronic heart failure (CHF) is a leading cause of disability and death in the United States. It is estimated that about 40,000 patients suffering from end-stage CHF could potentially benefit from heart transplantation. However, because of the rapid progression of the disease and the limited supply of organ donors, many potential recipients die before a donor heart becomes available. Accordingly, mechanical circulatory support with an LVAD is commonly used in an attempt to prolong the life of patients awaiting heart transplantation.

An LVAD pumps blood from the left ventricle to the aorta, thus reducing the work of the heart while restoring systemic blood pressure and blood flow. The new study shows that this temporary resting of the heart may have long-term benefits.

The study compared the contractile functions of 15 patients with end-stage heart failure with those of seven LVAD-supported patients. The study found improved function after LVAD implantation. The study also analyzed tissue from 20 failing hearts for three important genes before and after LVAD implantation. This showed an upregulation of all three genes after LVAD support, indicating that LVADs can actually induce molecular changes within the failing heart.

"This study provides exciting evidence that LVADs induce biochemical events in the heart consistent with recovery," commented the lead author, Dr. Paul M. Heerdt, Associate Professor of Anesthesiology at Weill Medical College of Cornell University and Associate Attending Anesthesiologist at both New York Weill Cornell Medical Center of NewYork-Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center. "It shows that LVAD support can improve the contractile strength of intact heart muscle and reverse the abnormal-heart-rate-related contraction characteristics associated with end-stage heart failure."

This research is the latest in a series of studies performed in the laboratory of Dr. Daniel Burkhoff, Associate Professor of Medicine at Columbia University College of Physicians & Surgeons, aimed at understanding how resting the heart by LVADs will lead to new approaches for treating heart failure. "We believe that the recovery of heart structure and function induced by LVAD support can form the foundation upon which new therapies to achieve a more complete and permanent cure for heart failure can be based," said Dr. Burkhoff. "Furthermore, if the molecular events underlying recovery of end-stage failing hearts can be pinpointed, approaches could be devised to achieve the same thing much less invasively than through LVAD use."

The study represents a collaboration between NewYork-Presbyterian Hospital's two major academic affiliates: Weill Cornell Medical College and Columbia University College of Physicians & Surgeons. In addition to Dr. Heerdt of Weill Cornell and Dr. Burkhoff of P&S, the other co-authors are Drs. Jeffrey W. Holmes, Bolin Cai, Alessandro Barbone, John D. Madigan, Steven Reiken, Mehmet C. Oz, and Andrew R. Marks of Columbia P&S, and Dr. David L. Lee of The Hospital for Special Surgery.