Solving the Mysteries of Heart Disease

by Gerald D Buckberg

  Figure 1: Bronx Project T-shirt, showing sick dilated heart on left and restored heart on right. The description is on accompanying video.

  Video 1 of Bronx Project: Narration describes reasons for its name.

  www.vimeo.com/buckberg/the-bronx-project

  My vantage point of history guided me. I was from New York City, and knew that “The Manhattan Project” team developed the atom bomb to kill people to end World War II. Our job was to save people, so I called our group “The Bronx Project” after the borough where I was born, to celebrate our anticipated triumph in successfully overturning heart failure. (see Video 1)

  Shirts in hand, all was set for our conference. I was also delighted that John Kirklin from Alabama would join our meeting to help us plan, and give his thoughts about the potential for our effort. He had been a mentor to me, and his presence added to the curiosity and scholarship needed for this new undertaking.

  All international team members were there, including representatives from our U.S. centers: the Cleveland Clinic, University of Virginia, Columbia University, Methodist Hospital in St. Louis, Carraway Hospital in Birmingham, and UCLA. The brightest of the bright sparkled, with Kirklin and Fontan being the most famous surgeons in the United States and Europe, respectively.

  Each cardiac surgeon was joined by a cardiologist, a pairing crucial to our mission of collaboration between surgeons and cardiologists. We had a busy room of 40 people, and the dialogue of the full-day event was superb.

  My recommendation to change our methods of protection from cardioplegia (in which we stop the heart) to a method of operating on the beating heart (Batista’s approach) was a surprise to the group. Indeed, it challenged a tradition that I had helped create, but I also knew it was the best technique in these circumstances.

  Everyone looked at me, stunned. “You are the guru of cardioplegia and you’re saying to let the heart beat?”

  “That’s exactly what I am suggesting. Especially since the area being operated on is dead and never moves.”

  I thought my decision would become a motivator for everyone to maintain such an open mind. My belief is the educational book never closes, and growth is not possible unless we are free to modify established methods.

  Yet there is never a smooth pathway when climbing the hill to a new peak. My suggestion to change myocardial protection methods was viewed as a dramatic turnaround. Francis Fontan was astounded and loudly objected, and John Kirklin declared that our entire ventricular rebuilding collaborative effort had no future!

  The first test of this team emerged. Such divergence of opinion was exactly the reason for my forming this group.

  Stagnation comes from being surrounded by people who only agree with you. Plus, while Fontan and Kirklin were my heroes, they were also human. Their reactions did not properly reflect their wisdom, but matched reactions I have encountered throughout my career. I was undaunted, because decisions are based on truth, not upon opinions. Unfortunately, the conflicting tenor of this interchange prevented me from distributing the T-shirts… and the naming of our effort was postponed.

  Subsequently, Francis Fontan tried the method of performing surgery on a beating heart, recognized its usefulness, and declared, “Bravo.” He listened, thought, and acted. I also visited him in Bordeaux, France and he was thrilled to receive the Bronx Project T-shirt. John Kirklin would later be delighted to learn of the superb results of our group’s effort, and became a supporter.

  This is one of the virtues of splendid collaboration, as changes evolve when open-minded participants with opposing viewpoints… will subsequently use evidence as the basis for shifting their positions. Truth wins, not reactions. This differs vastly from the unbending views that characterize those with rigid thinking.

  I was thrilled, because the actions of my heroes demonstrated exactly what champions are about.

  Grand Adventure Begins

  After our meeting in Boston, we agreed to meet again five months later in Brussels. In the meantime, surgeons in our group began performing these ventricular restoration procedures. To get this going, I visited U.S. centers to “scrub in” and assist them during their first case of ventricular restoration. Each operation was performed upon on a patient with a scar in a ventricle that had a normal (unscarred) heart surface. Interestingly, although our prior outcomes had achieved repeated success… the new surgical teams routinely anticipated a difficult post-operative recovery for these high-risk patients.

  For instance, upon entering the operating room in one prominent East Coast center, I noticed they had a left ventricular assist device ready for use, as well as a bottle of nitric oxide. The senior surgeon explained these were typical precautions used in extremely sick patients, as the assist device will support a failing heart and the drug infusion can open narrowed lung arteries. This patient was very sick and they expected he would still be very sick after we finished.

  But I countered, “No, I expect he is going to do well, as the procedure is really straightforward.” I supported this contention by suggesting that “I help the resident perform the operation,” and this is what we did.

  Surgeons are often known to have a certain “panache,” or preconception that colors our actions. For example, as the resident was performing the operation, the senior surgeon interjected that we should use a continuous suture to allow the procedure to move more rapidly — even though he had never performed this surgery. I politely said, “I’ve done a number of these procedures and interrupted sutures seem to work better, so let’s try this one that way.” We agreed and the case went smoothly, with excellent heart performance.

  I needed to return to Los Angeles in the early morning, and when the flight had a stop in Dallas, I called the office of the senior surgeon to get a follow-up. I learned all was well with the patient, and the surgeon was in the operating room. His assistant transferred my call to the OR… and I asked the nurse to tell “Dr. Continuous” that “Dr. Interruptus” was on the phone.

  A roar of laughter was transmitted from their East Coast operating room to Dallas. Everything was good.

  No Tussles in Brussels

  Five months after our Boston gathering, we had our next group meeting in Brussels. By this time, about 200 operations had been performed by members of the group. The protocols created for the Dor procedure had been followed, and some surgeons had performed their operations on a beating heart.

  The overall results were outstanding, and matched the outcomes we had expected! Based on these triumphs, everyone agreed to expand the numbers of patients treated.

  I decided to use this meeting to bring up my idea for what to call our group. While I loved “The Bronx Project,” it was not met with widespread approval. Seemed like an incompatible mixing of my humor with their bleak view of heart failure. Alas, another name would need to be found.

  We agreed to gather together again at the next American Association of Thoracic Surgery conference. As it turned out, these collaborative meetings would continue annually for the next ten years.

  By Any Other Name

  Our group still needed a title. While visiting Connie in Birmingham, he and I brainstormed ideas that included “Cardiac Renaissance” and “Rebirth.” None of them seemed quite right.

  Then Chris Athanasuleas, Connie’s wife, suggested, “Why don’t you simply call it the “RESTORE Group?”

  Connie and I looked at each other. RESTORE was a much better choice!

  Aside from “restore” meaning “bring back to normal,” we believed our name should also describe our approach. Connie and I, and our cardiology colleague, Al Stanley, found RESTORE to be the pertinent medical word; it stood for Reconstructive Endoventricular (inside ventricle) Surgery, that returns Torsion (ability to twist), Original Radius (size), and Elliptical (shape of the left ventricle). It was adopted and has remained the name ever since.

  Remarkable Results

  As members of the RESTORE team began doing more and more of these successful procedures, w
e accumulated data showing the benefits of ventricular reconstruction — which we now called surgical ventricular restoration, or SVR. However, processing data from our participating centers became a major task, as our team was not functioning within a university, where statistical departments are readily available.

  Fortunately, Connie found our answer in Birmingham. The eminent statistician, Dr. William Siler, agreed to participate. Bill had previously run the statistics program at the University of Alabama, and worked brilliantly and tirelessly toward analyzing the data collected from our national and international centers. Vigor was his modus operandi, and our extraordinary 82-year-old colleague remained active by continuing to scuba dive. Aside from being thrilled by his learned contributions, Connie and I were astounded that his energetic existence seemed to be linked to chain-smoking cigarettes and a continuous consumption of Coca-Cola.

  Bill’s work analyzed the collected data from 1,198 consecutive patients that underwent ventricular restoration by our team members. Other parts of the “triple V” — coronary bypass grafting and mitral valve repair — were also performed as we changed the size and shape of the ventricle in these dilated hearts.

  Results were impressive.

  Traditional patients with advanced symptoms of congestive heart failure typically experience a 50 to 75% three-year mortality rate86, 88 — a disastrous outcome that rivals or exceeds death rates from cancers.

  Yet a very different picture emerged from the data analyzing outcomes in the 1,198 RESTORE patients. Operative mortality (death while in hospital) was 6% in these high risk patients, and their five-year survival rate was 70%.89 This was a new and dramatic finding of high long-term survival following treatment for advanced heart failure, and opened the door toward making even longer-term observations.

  Yet longevity may not be the best final evaluation criteria in congestive heart failure, as quality of life is perhaps more important. Remember my dad who visited the emergency room every two weeks and lost his vitality due to incapacitating symptoms. Such an awful outcome is transformed by ventricular restoration, as the RESTORE analysis showed only 22% of patients needed to be re-hospitalized for heart failure during this five-year period.90

  To help non-medical readers further appreciate the magnitude of this improvement, I provide here the worldwide benchmarks for symptoms of heart failure, as set out in the New York Heart Association Functional Classification. These are used to gauge how patients are doing:

  Class I — no symptoms

  Class II — symptoms occurring with mild exercise

  Class III — symptoms during walking on flat surface

  Class IV — breathless at rest and housebound

  The cardiac cripple exists in classes III and IV, which is called advanced heart failure. This was my dad’s fate at the end of his progression.

  Most of our patients were already class III and IV when the RESTORE Group took them on for ventricular restoration. Yet following ventricular rebuilding, 85% of them achieved class I or II category status, demonstrating the procedure’s benefits: providing a fuller, more functional life over a longer survival period. The reason for such contrast is evident in the linked video (video 2) of how the heart performs before and after SVR (surgical ventricular restoration) — as the dramatic return to normal performance becomes apparent.

  Video 2 of ventricular restoration: Spherical heart on left, with reduced function. After restoration (right), function returns to normal. (E.F is ejection fraction and LVESVI is left ventricular end systolic volume index) From the studies of Vincent Dor.

  www.vimeo.com/buckberg/surgical-heart-restoration

  Exploring statistics further, we find that 50 to 70% of those class III and IV patients who do not undergo ventricular restoration will succumb to heart failure or sudden death (arrhythmias) within the first two years. However, sudden death is particularly rare in RESTORE patients — likely because this lethal complication is avoided by shrinking the ventricular volume (the ventricle chamber’s size). A stretched ventricle chamber is the primary cause of the abnormal heart rhythms that cause sudden death.91

  Surprisingly, discussions on the origin of heart failure arrhythmias written by electrophysiologists (cardiologists that treat rhythm disturbances) have consistently neglected to mention “stretch” as the principal condition that leads to sudden death.92 The reason for this exclusion is that their looking at the electrocardiogram to determine the cause is quite different from looking at the abnormal rhythm’s source: the dilated heart.

  Hopefully, a new recognition of ventricle stretch as the primary cause will motivate others to address the dilated heart that produces these dangerous rhythms.

  Ventricular restoration accomplishes this task.

  NIH to Forward the Revolution

  The RESTORE team formally reported its initial three-year results: 86% survival, avoidance of sudden death, and functional quality of life markedly improved over that from conventional treatments.93 (These early findings preceded the five-year results that were just discussed.)

  As I’d hoped, these positive outcomes stimulated the National Institutes of Health (NIH) to develop and fund a prospectively randomized Surgical Treatment of Ischemic Congestive Heart Failure (STICH) trial. A “prospectively randomized trial” means it will compare results of patients having ventricular restoration and coronary artery bypass grafting — against patients getting coronary bypass grafting alone.

  The launch of this STICH Trial was itself memorable. The NIH invited our surgical luminaries to visit Bethesda, Maryland and meet with their director, Claude Lenfant (who would retire soon after), to offer us insight on how to submit a proposal for their financial support to test this new approach to heart failure.

  The participants included Vincent Dor, the father of this method to rebuild the heart… Francis Fontan, the most prominent heart surgeon in Europe… Lorenzo Menicanti, Dor’s student who had extensive experience… along with myself and a surgeon from Duke University.

  The meeting took place in an NIH conference room. It was a unique experience, as Lenfant had never met Dor or Fontan before, and their animated conversations in French made me think of the U.N. conferring at the beginning of a new meaningful endeavor. Menicanti was gracious and presented me with a Montblanc pen, with a card that read, “To the maestro, for organizing this powerful new assault on our common enemy.”

  We were all thrilled that NIH was creating a trial to further legitimize our results. This would help bring such treatment into the mainstream. For their part, NIH felt the outcomes we had already achieved were highly notable. They ultimately allocated $45 million for the study.

  The Show Must Go On

  Meanwhile, SVR procedures continued to be performed independently from the NIH study, by our team and by other surgeons worldwide who were encouraged by our findings. In fact, by the time the STICH trial would be started (about two years after our NIH meeting), similar ventricular rebuilding results were recorded in over 5,000 additional patients globally,94 documenting high survival rates despite advanced heart failure.

  Randomization was not done in those cases (that is, none of these 5,000 patients were treated without ventricular restoration for comparison), but the drama of these remarkable findings was inescapable. Predictably, their excellent results matched our initial RESTORE outcomes, and all outcomes remained vastly superior to those following drug treatment alone, or those having coronary bypass grafting (done both with and without mitral repair) — but without ventricular rebuilding.81, 82

  Some might question if there even needed to be a STICH trial, since we had over 6,000 patients (the RESTORE Group’s 1,198 plus the additional 5,000) that proved our procedure worked. But the medical community generally believes that a prospective randomized study (as the STICH trial was designed to be), when conducted correctly, is the best type of study to provide credibility.

  Thus, we happily expected the STICH trial to further advance this procedure into the mainstream. Natur
ally, we assumed they would duplicate our findings by following the established patient selection and restoration procedure guidelines.

  Never. Assume. Anything!

  Setting the Foundation

  My initial involvement with STICH was to lead the Surgical Therapy Committee, whose designated role was to ensure that the SVR (surgical ventricular restoration) procedure was properly performed, and that only patients who met the guidelines for why they had developed heart failure would enter this study. These “entry criteria” were determined by international experts who had ventricular restoration procedure background.

  Patient selection was straightforward. To be eligible for the study, they had to fulfill three criteria. First, be a heart attack patient with limited ejection fraction (emptying less than 35% of the blood in the ventricle with each heartbeat). Second, have increased ventricular volumes (ventricle enlarged to over 60 ml/m2). Third, their ventricle must contain a non-contractile (not contracting) area with a scar that occupied at least 35% of its perimeter. These criteria typically occur in heart attack patients that develop heart failure.

  Surgeons also needed to qualify to participate, by having previously performed the procedure in five patients, and showing (four months post-operatively) that their operation reduced ventricular volume by at least 30%… increased ejection fraction by 10%… and had less than 10% mortality.

  Fifty centers — both national and international — were selected to participate, and Duke University became the principal investigator that oversaw this study.

  All should have gone well.

  Off the Rails

  Unfortunately, it was not long before it became apparent that this trial was heading in the wrong direction. …A very wrong direction.

  First, the team of participants was changed, expanding to 127 centers — instead of only the 50 originally chosen. This meant that many surgeons and cardiologists who’d never performed surgical restoration joined the bandwagon. The STICH leadership disregarded the criteria requiring that participating surgeons must demonstrate they can perform a safe procedure to qualify.