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ACC 2012 opening session: To Epcot with BraunwaldMar 24, 2012 16:06 EDT
He is a humble genius, a brilliant scientist who in this century and perhaps in no other will ever require an introduction. As Dr Eugene Braunwald stepped to the microphone at this morning's opening session of the American College of Cardiology (ACC) 2012 Scientific Sessions in Chicago, he smiled. "Dr Holmes's introduction" and accolades were "slightly exaggerated," he quipped. The audience of several thousand cardiologists, researchers, and other cardiovascular healthcare providers quietly chuckled and then figuratively strapped themselves in. Reminiscent in every way of Disney's Epcot center and its tour of our humblest beginnings, today's presentation differed only on the focus of our understanding of history of coronary ischemia spanning to a time of hope for myocardial salvage and repair. As the first "Legends" series of guest presentations for the ACC this year, it was an absolutely marvelous and most memorable ride.
Could swear I smelled popcorn
As I reach the foot of the Cinderella castle, it is about that time that I smell hot buttery popcorn and when I begin to try to persuade our younger one to skip the Magic Kingdom and do Epcot first. Epcot remains my favorite theme park throughout my 16-year history of many park visits. It is one of the few places where one gets a strong visual of ancient history while planted firmly in the present and at the same time a marvelous bird's-eye view of projections for the future in health and general science. Dr Braunwald, as the grandest of all tour guides, this morning first paid homage to Dr Simon Dack (1909–1994), one of the founding fathers of the ACC. He then followed with the interesting caveat that 2012 is the "centenary" year of the publication of the first information on myocardial infarction. In 1912, Dr James Herrick (1861–1954) of Chicago published in JAMA "Clinical features of sudden obstruction of the coronary arteries." In that article, he stated, "The importance of absolute rest in bed for several days is clear" postinfarction. Unfortunately, "a few days became six weeks," Dr Braunwald observed, with a 30% in-patient mortality for acute myocardial infarction in his time of training. "On early-morning rounds to draw bloods, I'd find that some of our patients had slipped away quietly in the night in some of the rooms off to the side," he lamented. The birth of the coronary care unit in 1961 by Dr Desmond Julian then cut AMI mortality by 50%. "The remainder of the AMI deaths would then be from pump failure rather than ventricular fibrillation," he added.
The Universe of Energy," dinosaurs, and such
My favorite of all the Epcot attractions is housed in a dark cool structure at the Universe of Energy, where dinosaurs munch on fresh greens as we glide along on the still waters of ancient marshes. Orchestral strains swell to deafening heights as the narrator continues his tour. Evolutionists take heart as prehistoric humans are depicted in their delight at the discovery of fire and later the impact of the first wheel. Similarly, in the history of AMI therapy, Dr Braunwald and his colleagues added a most important link to the chain of events that would improve AMI mortality with the publication of "Factors influencing infarct size following experimental coronary artery occlusion" in Circulation in 1971. This "animal-studies only" publication was "our first real hope that medical therapy might reduce the size of an MI," he said. Then in 1976, Dr Evgeny Chazov, "a brilliant Soviet physician," extended this thinking to humans. The audience was then treated to ancient pre– and post–intra-coronary lytic angiograms that demonstrated that, despite the successful lytic therapy of an acute infarction, significant residual obstruction lingers. "Rapidly, IV fibrinolysis replaced the intracoronary approach," Dr Braunwald pointed out. "Then in 1988, TIMI-1 demonstrated the impact of a 90-minute reperfusion strategy on mortality. Over a 25-year period . . . IV streptokinase was followed by the addition of aspirin. Later, streptokinase was replaced with tPA. Soon thereafter, primary PCI was born and then was rapidly married to scaffolds, a practice we have come to know in this era as "stenting."
On to Spaceship Earth
Despite all of these new advances in our 100-year anniversary of recognizing that arteries that suddenly become blocked cause myocardial death and then very often the death of the organism that experiences it, "we still expect 610 0000 new myocardial infarctions this year." Dr Braunwald stated. "Is myocardial reperfusion a double-edged sword?" he rhetorically asked. "The calcium paradox, in which reperfusion raises intracellular calcium, and then the O2 paradox, where an increase in toxic oxygen radicals open the mitochondrial permeability transition pore causes mitochondrial damage, then myocyte death," he said. But current and future studies will address such entities as ischemic preconditioning with cyclic ischemia and reflow maneuvers. Remote ischemic preconditioning by utilizing the lower limbs in early studies seems to be affecting STEMI outcomes. Studies with cyclosporine infused prior to PCI in STEMI decreased creatine phosphokinase (CPK) release significantly at 72 hours, and finally, the latest addition to the ACS cocktail, rivaroxaban at a dose of 2.5 mg po bid plus ASA and a thienopyridine in ATLAS 2 TIMI 51 decreased death rates from 4.1% with placebo to 2.2%. Although there was increased bleeding, "there was no increase in fatal bleeding," he pointed out.
Finally, Mission Space
REPAIR AMI, published in 2010, reported that two years' post-MI, the intracoronary delivery of bone-marrow–derived progenitor cells produced more myocardial thickening and a better EF. Dr Roberto Bolli's smalll SCIPIO trial, funded by Jewish Hospital of Louisville, KY, demonstrated that 16 patients who received right atrial (RA) appendage–derived cardiac progenitor cells delivered an astounding and earth-shattering 13% improvement in LVEF. The CADUCEUS study, published in the Lancet this year, demonstrated a reduction in infarct size and an increase in viable myocardium, and the BAMI trial will enroll in the second quarter of this year to explore further arenas of stem-cell therapy. No doubt, vocabulary words that are common vernacular in the world of stem-cell research like "cardiospheres" and "cardiac progenitor cells" or "colony-forming cells" with such descriptors like CD34 or CD133 will creep into the language of everyday cardiologists like myself.
The future as projected by Dr Braunwald is bright for patients who suffer from profound myocardial damage, and the future of stem-cell therapy has never been so palpably close or the steady heartbeat of progress in the arena of heart failure therapy so clearly heard. Like all good Epcot rides, the Braunwald tour of past and future therapies in myocardial ischemia came to an end, leaving its participants with a strong sense of satisfaction but an even more optimistic yearning to draw the future more closely to us; a future fueled with the knowledge of gatekeepers who were present today, like Drs Braunwald, Bolli, Perin, Simari, Moye, and others, the elite among the experimental prototype community of tomorrow and experts in the repair of myocardial damage who walk among us today.
You may now exit to your left. Watch your step . . .