For example, coronary artery bypass procedures were the most common cardiac surgical operation between the 1970s and 2000. These were done to correct narrowed coronary arteries, which obstruct blood flow to the heart muscle — and will also restrict the cardioplegia solution from getting into parts of the heart during the surgery. Stated most simply, it cannot work if it cannot be delivered.
This was the future challenge I alluded to back in chapter 2, citing that many years later I would adapt the cannula that I invented during my military service to deliver cardioplegia solutions backward. It was at UCLA in the late 1980s when we adapted this cannula to provide retrograde (backward) delivery by inserting the cannula through a tiny incision in the right atrium.
The benefit of this is that there is no obstruction when you give the cardioplegia solution from the reverse direction. The heart becomes wonderfully perfused, and this approach became a godsend for surgeons performing coronary bypass operations.
Becomes Universal Innovation
As so frequently occurs, our new development led to a fresh question: should both forward and backward delivery of cardioplegia be used in any operation, not just when there’s a blockage with coronary artery disease?
The answer to this new inquiry became clear after we made a set of unexpected observations during an aortic valve replacement operation.
When we started giving blood cardioplegia forward (into the aorta), we sampled the venous blood exiting the heart and noted that it had the expected dark blue color. All was good — the heart was properly taking up the oxygen delivered by the blood cardioplegia. But after about two minutes, this exiting blood turned red again. To us, this meant we were giving more blood flow than the heart required — since its needs were low because it was decompressed and it had stopped contracting. It was natural for us to believe that all portions of the heart were receiving adequate flow, and that the heart did not need to take up any more oxygen.
But then our chief resident suggested, “Let’s try delivering retrograde cardioplegia.”
An interesting idea. So we gave the red (oxygenated) blood cardioplegic solution backward… and watched the color of the blood draining from the coronary artery openings. To our surprise, it was blue blood draining from these vessels! That meant the heart still needed to take up more oxygen from the blood than it was receiving from the normal forward cardioplegia — a possibility that only became apparent after we tried the backward delivery.
This unanticipated finding showed us that retrograde (backward) delivery entered areas that the forward flow did not adequately reach and nourish.
We realized this lack of full perfusion during forward blood cardioplegia delivery is true in any heart, and led us to develop a new protocol for forward and backward flow during all cardiac procedures.
This became the standard for cardioplegia delivery, and over 7 million of these modified cannulas have been used.
Life-Saving Erector Set
As a youngster, one of my favorite toys was the Erector Set, with which I spent hours in the solitude of my bedroom as I built new and exciting creations. Such innovative building tendencies — and our hunger for playful inventiveness — usually end as childhood stops. Yet I’m convinced that our minds retain the powerful desires associated with these innocent joys of accomplishment.
One of my most rewarding creations was the development of blood cardioplegia. Given the importance of what my team found, we pledged to translate our concepts into protocols — and devices — to deliver these treatments in simple, safe, and speedy ways so they could gain broad use.
Initial steps toward making this widely accessible began in 1980, when Shiley Inc. developed a blood cardioplegia device that could effectively administer its delivery. This device is shown alongside one that delivers cardioplegia in a water mixture that does not contain blood, in Figure 1.
Figure 1: Original devices to deliver (on left) crystalloid (water-based) or (on right) blood cardioplegia that also can efficiently change the solution’s temperature.
The next step was to develop a safe way to deliver the blood cardioplegic fluid, so that it could flow to the heart by either a forward path (via an artery) or a backward pathway (via a vein). Collaboration with Research Medical Industries yielded the development of a simple device that permitted delivery in either direction. (Figure 2)
Figure 2: Integrated system to deliver blood cardioplegia antegrade (into aorta) or retrograde (via coronary vein), together with a simple stop cock to change the direction.
Of course, an effective and reliable cardioplegic solution needed to be affordably manufactured, stored, and distributed. Two pharmaceutical companies, CAPS and Koehler, came through and within a short time, the solution was widely available in the United States and Europe.
The development of this entire blood cardioplegia delivery system was a game-changer. Now the cardiac surgeon had the ability to enter the operating room and utilize his or her own Erector Set during every cardiac procedure. That included me, as the residents liked to jest, “Uncle Bucky is having fun operating with his own devices.”
I felt gratified for having never let go of my child-like joy for innovation, and for now being able to share its fruits with others. In fact, in a moment of lightheartedness, I once teased a dear friend, Jim Barnard, who had made some playful observation about life, “Jim, when will you grow up?”
He paused a moment before he answered. “Bucky, I want to be just like you. I never want to grow up. I just want to grow old.”
I had to laugh. As adults, I think we secretly yearn for ways to resurrect our youthful past. When a child is fortunate enough to become a cardiac surgeon, their greatest reward may well be entering the laboratory and the operating room. For my own operative procedures, I will admit it has been exhilarating to use the techniques I designed.
If It is Good, Let Others Tell the Story
From the beginnings of our success in development of blood cardioplegia, its use naturally began to spread to others who would report their own positive outcomes.
This included Floyd (Fred) Loop at the Cleveland Clinic, an open-minded person who welcomed the improvements our methods offered over conventional techniques of myocardial protection. As it would turn out, my association with Fred would prove very fortunate in forwarding the widespread clinical implementation of blood cardioplegia.
A change to treatment methods like ours comes with one additional consideration beyond their effectiveness: the ever-present concern of financial costs. This was true in our case since use of our novel devices added an initial cost of $250 per operative procedure when compared to crystalloid cardioplegia approaches — which are simpler as potassium chloride is simply added to a liter of clear solution and delivered into the aorta.
Instead, our technology required use of a blood cardioplegia delivery device, a special catheter in the aorta with another in the coronary sinus, and a cardioplegic solution that must be mixed with the blood in the heart-lung machine before delivery. Hence, the additional $250 expense.
While that hardly seems a significant figure, when multiplied by thousands of patients, it becomes a consideration for any institution — and was causing some to be hesitant.
Seeking a better perspective, Fred and I discussed the whole cost of hospitalization, rather than just operating room costs alone. Fred decided to conduct a more complete evaluation.
Fred operated on 819 consecutive patients with our techniques, and compared his results with those of five other experienced surgeons who used conventional crystalloid cardioplegia on 2,582 Cleveland Clinic patients. The resulting data showed that patients receiving our blood cardioplegia experienced one day less in the intensive care unit and one day less in the hospital. After his reporting these outcomes to me, I asked Fred if it was possible to summarize hospital costs. He did — and the results showed that overall costs were $2,200 higher for each patient receiving crystalloid cardioplegia.
Not only that, there was an
entire additional group of patients called “outliers,” whose conditions (having impaired recovery after surgery) required extended intensive care unit stays and longer hospitalizations, and were not considered in his first overall analysis. Overall costs for these “outlier patients” were up to fourfold higher. Interestingly, the number of outliers who had received crystalloid cardioplegia was three times the number of those who got blood cardioplegia.
Consequently, even though our innovative changes in myocardial protection added $250 per patient in operating costs — it saved the Cleveland Clinic over $10 million per year (they did 5,000 operations) when you factor in follow-up care in the intensive care unit and overall hospital stay.21
Fred Loop’s analysis predicted that general acceptance of our innovative approach would save around $650 million annually, basing this savings on the 300,000 U.S. patients undergoing cardiac surgery each year at the time. Today, over 1 million cardiac procedures are done every year nationally and internationally, so these cost savings are amplified significantly more.
This financial analysis accelerated the adoption of our new methodology. The impact of our discoveries has only flourished in the 40 years since their beginnings. Today, 80% of surgeons worldwide use blood cardioplegia. Of those patients receiving blood cardioplegia, 6 million procedures were done with our blood cardioplegic delivery device, while 19 million patients received blood cardioplegia with comparable devices — such that over 25 million patients have now received blood cardioplegia. Additionally, over 4 million operations have been done with our retrograde catheter, and well over 4 million patients have received our specific cardioplegic formula during their operations.
While it is hard to calculate all the hearts that have been protected and how many lives have been saved from injury over the years, knowing that our work has expanded the safety and success level for the patient and for their surgeon provides me with the finest reward I could ever imagine.
The Investigator’s Path
Throughout my career, my research has always begun with the observation of a problem. But the path to finding a solution to each problem continually varies and is filled with fortuitous encounters, surprising outcomes, and unintended benefits.
For the discovery of blood cardioplegia, my journey began simply by listening to Dr. Kirklin’s observation of a heart that became stiff after receiving reperfusion to restore its blood flow. This led me to discoveries and a laboratory test where blending our two winning strategies of reducing calcium and raising pH in our reperfusion created worse results. Recognizing that this failure was based on an incorrect observation of ventricular fibrillation, led to our adding potassium that solved the true underlying problem, which created a protocol of multiple doses of blood cardioplegia. We then progressed to delivering them at different temperatures at various stages, in both forward and backward flows. My education came full circle as I even became a medical student again. I needed to relearn basic biochemistry in order to properly realize the value of understanding, and then using, amino acids to resolve a fundamental heart problem.
It was a series of many steps leading to a treatment method that is now nearly universally used as the primary form of cardiac protection. I have been extremely gratified by our accomplishment, which came nearly 20 years after I first observed the “heart more hurt than healed” during my internship at Johns Hopkins.
I would continue this pattern throughout my career: looking at a problem, taking three to six years to solve it, then moving onto the next problem.
I eagerly expected that our future discoveries, just like blood cardioplegia, would be equally embraced by the medical community to benefit the lives of patients.
I would find I was mistaken.
CHAPTER 8
You Don’t Have to Die
of a Heart Attack
My maternal grandfather, Zelig Levitt, had seven children and even more grandchildren. Grandpa was deeply religious and spoke mostly Yiddish. Yet none of us had trouble understanding him as he telegraphed his meaning through gestures, eye contact, and warmth.
He worked in the garment industry and had an ever-present twinkle in his eyes. Grandpa possessed grace and dignity, and was a role model whose lifelong dedication to hard work and persistence reflected his immigrant background.
Throughout my childhood, we celebrated Shabbat every Friday night with Grandma’s delicious old-world cooking. Grandpa sat at the head of the table, cracking jokes and making observations, all in Yiddish. He groaned with pleasure as he ate Grandma’s scrumptious kosher meals. His joy made us giggle and glad to be together.
His strength and vitality never waned, until the day I came home from school and found my mother crying on the phone. Grandpa was in the hospital. He had suffered a myocardial infarction. In layman’s terms: a heart attack. As a 14-year-old who knew nothing about the human heart, I struggled to understand how this could have happened so suddenly. There were no warning signs. One day, he was hard at work and the next he was in the hospital, hanging on by a thread.
We raced to the hospital to see him. His doctors met us in the lobby and told us the hard truth: it didn’t look good. “When a heart attack comes on suddenly,” said a man in a white lab coat, “25% of people don’t survive.”
Tragically, the doctor was right. Grandpa died in the hospital two days later. The man who was larger than life, always so full of strength and vitality, died in a narrow white hospital bed. He never knew what hit him.
Family Affliction
Sadly, this was not the last brush with heart disease in my family. Many years later, I received a call from my father, who by this time was living in Florida.
“Hi Gerald,” he said, his voice as bright as ever. But I knew something was wrong immediately. My father hated talking on the phone, so his calls came only in times of need or emergency. By now I was an adult, and an M.D. My father wasn’t just calling his son; he was calling his physician.
“Dad, how are you?” I asked, deeply concerned.
“Oh fine. Listen, I just had something happen that Mom wanted me to share with you. I was out on one of my walks, enjoying the evening, and all of a sudden I got a very strong sense of….” He cleared his throat. “Well, it was a crushing pain right in the middle of my chest. Like an elephant sitting on my breastbone. Couldn’t breathe. Funniest thing. Totally stopped me in my tracks. Do you have any idea what that might have been?”
I did. I asked him to describe if he had experienced any involuntary movements in reaction to the pain.
“Well, as a matter of fact, as pain shot down my arm — my arm raised and my hand just came up over my chest, clenched like a fist.”
“Which hand?”
“My left one.”
Dad had just described a textbook example of angina, or heart pain, which comes from impaired blood supply to the heart. While I had the natural concerns that a son would have for his father, I needed to keep on my doctor’s hat. I sent him to promptly see a cardiologist. They found he had a classic case of atherosclerosis — a substantial narrowing of his coronary arteries.
I wanted to make sure no additional heart damage occurred before his symptoms could be addressed. He was admitted to a Florida hospital. I called the surgeons at that facility to learn if they were considering operating on my dad. I wanted to know how they would protect the heart during his cardiac procedure. From their answers, I was not confident they would conduct the operation using the guidelines I had established. So as soon as my father was stable, I flew down there and brought him back on a plane to UCLA where he would be cared for by my colleagues if a coronary bypass became necessary, using the intermittent ischemia techniques we described at the AATS (this problem with Dad happened before we had created our cardioplegia approaches). It turned out that a coronary artery bypass was needed, and so three vein conduits were grafted (transplanted) from his leg onto his coronary arteries. These conduits detoured blood flow around the blockages within his coronary arteries to resto
re blood supply to his struggling heart.
Fortunately, tests afterward gave us good news. They showed his heart still had excellent function. We’d avoided the heart attack that would have inevitably followed if he’d been left untreated, and caught the symptoms early enough that he suffered no permanent heart muscle damage.
Fifteen years later, Dad wasn’t so lucky. My parents had retired to Tamarack, Florida and were enjoying a new life of leisure when Dad’s chest pain came back. He went in for more tests, which showed that two of the three grafts had closed. More importantly, several sections of the heart muscle were no longer functioning properly and the heart was dilated. Another coronary bypass procedure was performed and he had another good recovery. But it was clear that at some point, he had suffered a “silent” heart attack and the permanent damage to his heart was severe.
The term “silent” means there are no warning signs and the heart attack happens without chest pain. Unfortunately, the dark legacy left behind by a heart attack unfolds over time, as damaged heart muscle dilates (stretches beyond normal size) to cause the late symptom of heart failure.
Soon after, they discovered a tumor on his colon and admitted him for an abdominal procedure. In a patient with heart problems, even the simplest surgery can be life threatening. I caught the next flight and joined my worried mom. Early on the morning of the planned procedure, the nurse called to tell us that the procedure had been delayed because Dad was having difficulty breathing.
Mom and I drove to the hospital in silence. I’m sure we were both thinking of Grandpa Zelig and how we had rushed to the hospital all those years ago; how our worlds were rocked by his untimely death two days later. Together, we hurried down the halls to Dad’s room where we found him awake and aware, but struggling miserably to take a deep breath. I grasped his shaking hand and reassured him that everything would be okay. He believed and trusted my judgment… but I knew that the damage to his heart wouldn’t heal this time. Dad had congestive heart failure.
Solving the Mysteries of Heart Disease Page 11