ACC 2012 opening session: To Epcot with Braunwald

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 . . . 

Your comments

	ACC 2012 opening session: To Epcot with Braunwald
	# 1 of 4	March 25, 2012 08:03 (EDT)
	James Adrian	Thanks, gives a good perpective.
	# 2 of 4	March 27, 2012 12:20 (EDT)
	Jean-Pierre Usdin	thank you  professor Braunwald! I remember  my first handbook, when I decided as an intern to choose the cardiology (my speciality), was "Heart Failure " by E. Braunwald a marvelous red book small sized always close to me that I opened (an red) so many times.  I had so many difficulties in France to order this book (it was in last 70's -a long time ago-Amazon and so were not born) when I finally received it I could not believe my eyes it was so great . I have alwas this book in my office with this red cover...beside one of "The Heart" hand book. now with Internet and iPad (4!) we do not buy many hand books, and souvenirs passe unmaterialized in our USB Keys... we spare space but "nostalgy is not was it used to be" (S Signoret) thank you pr Braunwald, I had the great oportunity to see and listen to you in the last ESC congress in Paris it was an unique moment for me.  thank you Melissa for this paper (as usual very good moments in our "leisure" time) Jean-Pierre Usdin Paris. France.
	# 3 of 4	March 27, 2012 02:36 (EDT)
	Maurice Chew	Thank you Melissa for this very interesting update on the latest ACC  Scientific Session in Chicago.  It has been more than a quarter of a century ago since Dr Eugene Braunwald came up with the idea of thrombolysis in the treatment of MI (TIMI risk score).    His  ingenious presentation today puts into perspective --that treatment of ACS is not just about PCI and revascularisation with the insertion of latest drug eluting stents. There is more to the story - as the calcium paradox and O2 paradox has shown. That significantly more benefits can be had with the latest cocktail of OACs-- rivaroxaban and thienopyridine     Thank you also for giving us an insight into the latest trials with stem cell therapy with cardiac progenitor cells. I am sure that even the skeptics will agree that this will in the very near future become the definitive treatment for heart failure and may even reduce the need for heart transplantation
	# 4 of 4	March 30, 2012 09:45 (EDT)
	Carlos Monteiro	There are some missing points: 1) "Herrick’s Coronary Thrombosis (Thrombogenic) Theory In his classic paper written in the early 20th century, James Bryan Herrick (besides presenting his proposition of a pathophysiological triggering mechanism) wrote of his therapeutic experience using digitalis and strophanthin for angina pectoris and coronary thrombosis: "…If these cases are recognized, the importance of absolute rest in bed for several days is clear. It would seem to be far wiser to use Digitalis, Strophanthus or their congeners than to follow the routine practice of giving Nitroglycerin or allied drugs. The hope for the damaged Myocardium lies in the direction of securing a supply of blood through friendly neighboring vessels, so as to restore so far as possible its functional integrity. Digitalis or Strophanthus, by increasing the force of the heart’s beat, would tend to help in this direction more than the Nitrites. The prejudice against Digitalis in cases in which the Myocardium is weak is only partially grounded in fact. Clinical experience shows this remedy to be of great value in Angina, and especially in cases of angina with low blood pressure, and these obstructive cases come under this head. The timely use of this remedy may occasionally in such cases save life. Quick results should also be sought by using it hypodermically or intravenously. Other quickly acting heart remedies would also be of service." Herrick’s priority in his treatment approach was to preserve the myocardium in front of coronary thrombosis. This clinical approach was largely ignored by his colleagues; perhaps it didn’t sound plausible, possibly due to the absence of experimental support. Or perhaps Withering was right in his despair of trying to explain a remedy (see above quote). Regardless, the fact is that Herrick’s therapeutic approach isn’t largely discussed at medical schools or in scientific papers. As a result, most physicians remain in total medical ignorance about his clinical practice in the treatment of angina and acute myocardial infarction (AMI), also known under the general term "heart attack". Herrick’s Thrombogenic Theory was adopted, but his therapeutic conduct was forgotten. "The cardiac patient does not die from coronary disease, he dies from myocardial disease!" George E. Burch, cardiologist and teacher, 1972" 2) Dr. Quintiliano de Mesquita from Brazil was the first to prescribe an earlier deambulation after the myocardial infarction, in 1972. Please see the summary in English of his book published at internet at www.infarctcombat.org/LivroTM/parte8.htm ""The cardiotonic is responsible for an early and sure deambulation; in the infarctioning clinical picture, with an arrested or avoided infarction, it takes place in the 5th day; in infarction it takes place in the 10th day, with discharge from hospital the following day; a 0,4% mortality rate has been observed in connection with early deambulation." 3) Referring to the point cited by Braunwald that "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", it is necessary to stress that the clinical effectiveness of the CCU has not been closely studied, and previous studies are suspect due to high degrees of bias and other confounding factors. Despite the few studies available examining the issue, most have concluded that CCUs offer no significant reduction in mortality rates, as compared to rural hospitals without these complex units (Goldman, 1982; Hill et al., 1978). Reference: 1) The Coronary Care Unit: Miracle of Modern Medicine or Technology Out of Control? Daniel Rosenfield, The Meducator, Volume 1 | Issue 9 Article 9, 1-18-2012

You must be a member (with full membership) to post a comment.

Already a member?

Enter your login information below:

 Remember me on this computer

Forgot your username and/or password?

        Login        

Enjoy all the benefits of theheart.org

With full membership, you can check out our educational and editorial content, search the site, receive our newsletters, join discussions, download slides and much more.

Membership is free!

    Join now for full access