Translation, Translation, Translation

• hemodynamics
• diagnostics
• interventional cardiology
• translational research

Three factors dominate the calculation of real estate value: location, location, and location. As I enter the second half of my editorship of Circulation Research, my reflections pinpoint translation, translation, and translation as the three critical factors dominating the future of our journal. This reflection has its roots in personal ruminations about the field of clinical cardiology and how it has evolved and is evolving today.

Cardiology now finds itself in a defining epochal transition. We are on the threshold of a new Golden Age. Two Golden Ages have preceded that which we are just entering (see Table). In the 1970s and earlier, we experienced the Classical Age. This era was, necessarily, largely descriptive and observational; diseases were classified and codified, taking advantage of newly elucidated principles of fundamental hemodynamics and the development of key diagnostics in the catheterization laboratory, electrocardiography, and echocardiography. Even in this early era, however, Cardiology stood out among nonsurgical subspecialties in that our discipline actually intervened to reverse disease. What better testament can there be to Cardiology’s progressive ethos than the creation of coronary care units (CCUs)? Such units were conceived so that rhythm disturbances could be quickly recognized and treated by cardiopulmonary resuscitation, external defibrillation, or pacemakers. Such therapies, which revolutionized the practice of medicine, were hardly descriptive or observational. But the practice of cardiology relied on basic science only insofar as basic physical principles of pressure, flow, and electricity were concerned; biology was a curiosity, lamentably peripheral to the daily practice of medicine.

The 1980s and 1990s ushered in the second Golden Age of Cardiology: the Interventional Age. Cardiologists pioneered active methods to correct plumbing disorders (angioplasty and stents), whereas cardiac electrophysiologists developed implantable cardioverter-defibrillators and ablation. Suddenly, Cardiology was transformed from a subspecialty with a wait-and-see attitude to one in which a number of anatomical disorders could be corrected percutaneously. Still, the practice of cardiology remained rooted in principles no more biological than those required to fix an automobile. The field of thrombolysis was a prominent exception, as it required the recognition of the existence of biological fibrinolytic agents. Nevertheless, the progress of Cardiology still hinged only marginally on prior basic science work. Meanwhile, those of us working in basic science saw little evidence that our efforts would ever make much of a difference in the practice of clinical cardiology.

All this has changed with the emergence of a new Golden Age: the Translational Era. In this era, fundamental biological principles are harnessed and translated into changes in the practice of medicine. The first breezes heralding the onset of this age were the development of coated stents to inhibit coronary restenosis and the creation of abciximab, a monoclonal antibody fragment targeting the GpIIIb/IIa receptor. Neither would have been possible without sophisticated understanding of the underlying biology (for coated stents, that of vascular cell proliferation; for abciximab, that of platelet aggregation). The first breezes have recently turned into raging gales. The stem cell field is illustrative of just how fundamental, rapid, and revolutionary translation has become. Whatever we think of the controversy regarding the use of bone marrow stem cells for regenerative therapy,¹ its impact on clinical practice is undeniable.² Meanwhile, the recognition that the heart is not static but rather sustains turnover and self-repair has opened up dramatic new possibilities for autologous therapeutics using resident cardiac stem cells.^3–8 Soon, we may be able to harvest stem cells from a patient’s own heart, expand them in vitro and then transplant the cells back into the same patient’s heart. This is a dizzying prospect given that we did not even recognize the existence of resident cardiac stem cells two years ago! Consider the transforming potential of other new technologies: gene therapy, genomics, proteomics, nanodevices, and hybrid therapies. The prospects are sufficiently heady to embolden us “basic scientists” who publish in Circulation Research to believe that we may, soon, make a real impact on clinical cardiology.