Solving the Mysteries of Heart Disease
Page 19
The lack in understanding the causes behind these lethal occurrences is readily apparent from the actions occurring in hospital hallways. Sudden death is confronted by Code Blue teams that rush in with their crash carts. Their only goal is restoring normal heart rhythm. There is no consideration of why the heart stopped and how to remedy this.
So why is this short-sighted?
Because sudden death is not a disease, but a symptom of the disease that produced it. This implies that something else is needed beyond simply restoring a heartbeat.
While CPR would continue to be used to maintain critical brain nourishment during sudden death (since brain damage in the rare survivor will impair mental capacity and later cause their premature death) — I knew that developing a fresh strategy to discover and fix the underlying reason for the sudden death was also essential.
Brain is the Key
It has been common knowledge that “irreversible” brain death develops when blood flow is stopped for four to five minutes, so that the primary focus has been to nourish the brain (with CPR) while at the same time trying to return function to the stopped heart.
Yet it is also crucial to ensure that the brain continues to have adequate blood flow after the patient’s heart starts to beat again. This is not an easy task, because most of the rare sudden death survivors develop a weakened cardiac function from their underlying damaged heart muscle. This accounts for much of the severe brain damage that develops in half of the 10% of surviving patients. It is why the conventional approach of “treating the heartbeat” instead of “treating the cause of the heart malfunction” creates the reason that brain damage occurs.
Until I realized this, my approach had been like that of others: to save the heart, but lose the brain. An unacceptable trade-off. But what else could we do?
Journey Begins
The path before us seemed clear. Our prior experimental and clinical studies on heart attacks documented that the heart can be fixed. While we clearly needed to do this, I believed it was also critical to find a way to sustain an adequate brain blood supply during — and after — the sudden death event.
This brought up the same enduring question that began when I was at Johns Hopkins: why did some patients survive, when most do not?
I remained perplexed. Could the answer to this mystery be the unattainable holy grail of cardiac medicine? The challenge to finding a solution seemed overwhelming. I was highly motivated, but it was still natural to question if a solution was possible.
Read on and you will find, just as I did — that answer is yes.
Changing the Study
At the time, we weren’t studying sudden death, but rather, trying to find out what happens during an acute heart attack (caused by closing one artery)… under conditions where there is also narrowing in the artery that supplies the remote muscle. We used pigs as the test subjects, as their circulatory system is similar to ours (as mentioned before, pig heart valves are sometimes used to replace human valves).
Such conditions (one artery closed and another narrowed) imposed a severe affront to the circulation, and sudden death occurred in 80% of these pigs as they developed ventricular fibrillation. It was irreversible, despite our multiple attempts to defibrillate this quivering state. Their deaths mirrored the high mortality of patients who sustain sudden death.
A German research fellow, Friedhelm Beyersdorf, was the leader of our study. Very bright and inquisitive, he came to me with a new approach.
“We’re studying the changes after a heart attack, but we’re losing the animals. We know that controlled reperfusion will save the heart muscle after it has been without blood supply. So why not do that same treatment to pigs with a heart attack that develop the irreversible ventricular fibrillation that causes their sudden death? I think we can save them.”
I looked at him a moment… and grinned. “That is a great idea. Let’s do it!”
We weren’t focused on sudden death until he raised that possibility. But I instantly recognized that it was a prime opportunity to try to address this almost untreatable clinical event — that causes a catastrophic 85 to 90% mortality.
As team members shared ideas, the excitement grew. Our collective pride blossomed as we designed a unique approach to this problem. But we still needed to take the second step.
We had to test it.
This pattern differs from traditionalists who might say, “I don’t think that’s possible and we’re not going to spend time and deplete our precious funds on it.”50 But as I’ve said many times, conventional thinking is not my approach, for it creates a barrier to considering what might be attainable. Especially when a near fatal illness (85 to 90% mortality) may be conquered.
Perfect Conditions
The medical conditions we were creating in our test subjects as we studied acute heart attacks were perfectly suited for this new direction of research, as most sudden death patients also had narrowing of more than one coronary artery.
We worked out the details with Friedhelm after listening to everybody’s ideas. Our underlying premise, based upon prior studies, was that damaged heart attack muscle can be saved and recover function. This approach “treated the heart,” rather than followed the typical focus of simply “restoring the heartbeat.” It differed from traditional attitudes, where the heart attack’s cause that triggered the sudden death was not of immediate concern, since that could be corrected later in the rare survivor.
We were motivated to find a different approach that immediately dealt with the cause, since we knew the weakened heart would not function optimally even after the heartbeat was restored. Poor heart performance could cause death in the resuscitated patient in the hospital or soon thereafter. Even if it did not cause an early death, impaired heart function will still lead to brain undernourishment (and damage) in survivors.
The question now became: how could we treat the cause of the heart attack while we were reversing sudden death? This approach, if possible, would save the heart and the patient — and might avoid the all-too-frequent brain damage. In other words, our new target created a powerful dual goal: remedy the heart attack and avoid the brain damage at the same time.
Indeed, we were “outside the box” with this proposal. But that is the essential step in the evolution of dramatically new treatments.
Our New Study
I knew that reproducing real world clinical events was crucial to our designing and testing new treatments.
First, the brain needed to have adequate nourishment during the initial treatment of sudden death, so we made sure the CPR would keep blood pressure at or above 60 mm Hg. A key ingredient to this was having the blood pressure monitored through every stage of treatment. If the pressure ever went down, we sped up the frequency of compressions, raising the rate from the typical 60 compressions per minute up to 100 (100 is now the officially recommended CPR compression rate).
Step two was to recognize that CPR still does not ensure adequate blood flow to all the organs. So we believed the subject should be brought to the cath lab to be promptly placed on the heart-lung machine to fully take over pumping blood and lung ventilation. This intervention can be done without opening the chest, as we simply puncture the skin to access the blood vessel, much like one does with a needle and tube for an intravenous drip. This sequence exactly parallels how we treated acute heart attacks (Chapter 9), permitting us to directly treat the cardiac cause of sudden death.
Step three was to provide controlled reperfusion into the region that had undergone an acute heart attack, mirroring the approach we described in Chapter 9.
Reproducing Reality
To imitate the likely scenario that develops from these fatally fibrillating hearts, we induced sudden death conditions in animal test subjects. We first performed CPR for two hours to mirror the time needed to transfer a “patient” from the field to the hospital and directly to the catheterization lab to diagnose the cardiac reason for sudden death. The heart-lung machine is initi
ated in the cath lab and the diagnosis of the cardiac cause can be determined. An additional hour (using the heart-lung machine) is then added. This mirrors the transfer time to the operating room and the interval needed for delivering controlled reperfusion for the cardiac cause of sudden death. Blood reflow to overcome the remote muscle’s narrowed artery is also done.
So the heart-lung machine was kept on for a total of two hours — the first for making the diagnosis and moving the patient to the operating room. The second hour represented the time we needed for delivering controlled reperfusion into the acute heart attack region and for bypassing the remote muscle’s narrowed artery.
Success
Our findings tell the story.
There was 100% survival using the innovative method, which is in sharp contrast to the typical 85 to 90% mortality with conventional sudden death treatment. Heart function completely returned to normal, and each heart attack region recovered substantial function despite three hours without blood supply.51
This was stunning. We had found a reproducible way to treat sudden death! Our mood was euphoric and we congratulated each other.
As our focus centered on survival from sudden death, we did not evaluate neurological damage. We knew the brain received adequate blood pressure during CPR, and heart performance was similar to what is expected following a routine elective operation. We anticipated that brain function would be successfully retained because it always had flow at a high pressure (delivered by CPR), but realized that subsequent testing would be needed to make sure.
This great experimental triumph intensified our desire to apply this new treatment method to a patient with sudden death due to irreversible ventricular fibrillation — an event where anything more than just 15 minutes of CPR reduces the survival rate down to below 1% and there is consistent severe brain damage in those rare survivors. Essentially, we needed to see if our approach would save the life of someone whose survival was otherwise impossible.50
We didn’t have to wait very long.
One morning, I had performed a routine valve replacement. The procedure went well. The new aortic valve was in place and heart function was excellent. The patient was to be moved back to the intensive care unit (ICU) and I returned to my office, satisfied that things had gone as planned.
Until I got a call: the patient’s heart had developed ventricular fibrillation as he was wheeled back to the ICU — it caused sudden death!
“Doctor Buckberg, we’ve been doing CPR, but all attempts to restore his heartbeat have not yet….”
I didn’t wait for further details. I hung up and rushed to see the patient, grabbing a member of my team along the way. We hurried to the hallway where interns and residents were administering chest compressions and supplying ventilation.
“Clear!”
Everyone stepped back as the defibrillator paddles were activated. The patient’s body arched from the shock… but effective heart rhythm was not restored.
“Clear!”
They tried again. Again, no change. Seeing the resident who’d been giving CPR was tiring, I had my team member take over, while I checked the blood pressure reading on the monitor — it was barely 60 mmHg. My team member increased the rate of chest compressions to 100 per minute, as we wanted the pressure kept over 60.
I sent a message to others on my team that we needed to immediately go to the operating room and deliver controlled reperfusion. We were told all rooms were in use and they were not sure how long before one would be available.
More CPR and unsuccessful attempts at defibrillation continued as we waited for an operating room. It had already been 25 minutes and I saw the residents, interns, and nurses checking watches.
Remember, accepted conventional thought was that patients could not survive if receiving CPR longer than 15 minutes without restoring a heart rhythm.
I took over performing chest compressions from my tiring resident. We continued in vain to restore a heartbeat and waited for an OR. We were now at 45 minutes of CPR.
Finally one of the residents tentatively said, “Doctor B, I know he is one of your patients, but it’s been over 45 minutes. There’s very little chance of him recovering at this point. Really none.”
“Well, I don’t know that, not at all,” I replied. “Here’s what I do know — the heart is working because I’m compressing it. The brain is alive because we are maintaining a good blood pressure — it’s never had lack of nourishment. I can fix the heart with controlled reperfusion, and I suspect the brain will be undamaged as long as we maintain a good blood pressure to perfuse it. We just need an operating room.”
As you might imagine, they thought I was foolish. They didn’t know of the successes we’d had in our lab… something I deeply hoped we could now duplicate.
Finally, an OR opened up and we brought our patient in. The rest of my team was ready and I put the patient on the heart-lung machine. I had already fixed his underlying cardiac problem. He had not suffered a heart attack, but we used controlled reperfusion to counter his ventricular fibrillation, just as we had in our test animals.
But would it work?
He responded beautifully! His heartbeat came back strongly, and we were able to take him off the heart-lung machine in routine fashion. His heart purred along!
Plus — he awakened promptly and there was no brain damage.
Suffice it to say, our whole team was ecstatic. We’d just done the impossible! Of course, the impossible is only impossible… until it isn’t.
We applied our novel approach in 14 patients at UCLA. Thirteen patients had complete recovery of the heart (measured five to seven days later), while one patient succumbed to brain damage and death. These findings contrast sharply with results following conventional sudden death treatment (where brain damage develops in half of the 10 to 15% patients that recover cardiac function). By contrast, good brain function existed in 13 of our 14 patients.52
These were remarkable findings. We were thrilled!
Spreading the Word
I shared our findings with other surgeons — colleagues and friends I knew personally — as well as through presentations I gave at medical conferences. Indeed, these were the findings I shared with Connie Athanasuleas at the Duke University meeting, as described in the first chapter. I asserted that the traditional belief that there is 100% mortality of patients receiving CPR longer than 15 minutes is simply not true. I went on to explain that this innovative treatment involves three management principles:
Make sure the brain doesn’t die by giving CPR at a rapid rate to maintain sufficient blood pressure.
Use the heart-lung machine to support the body and discover the underlying cause of the sudden death.
Repair the heart region so it can function normally, followed by controlled reperfusion rather than using only normal blood supply.
Ours was a new approach that differed radically from the norm. And while I knew everyone was horrified by the high mortality normally associated with sudden death, I correctly anticipated there would also be enormous resistance to initiate a treatment that was so unlike what they were used to.
But that did not bar some who listened, were eager to learn, and applied the approach themselves. Subsequently, our integrated treatment would be used in 34 sudden death patients in different centers in the U.S. and Europe, with equally outstanding results. Patients underwent an average of 72 minutes of CPR (ranging from as short as 20 minutes to as long as 150 minutes in one of our own cases) and had a 79% survival rate — with only 5% developing brain damage.53 As with our original test subjects, the patients’ response in heart performance mirrored what would be expected from a routine heart operation. None of the typical complications expected with sudden death patients occurred.
Our approach, including a greatly extended use of CPR, was certainly novel. Yet the outcomes demonstrated that patient survival can occur after far longer time frames than those predicted by the traditional concept that “greater than 15 minutes of
ventricular fibrillation is an irreversible condition.”
Sometimes much longer.
I encountered such an extended duration in a patient of mine who experienced sudden death in the ICU. We had already repaired her underlying heart problem, and only needed to get her back to the operating room to give her controlled blood reperfusion to remedy the otherwise irreversible ventricular fibrillation.
Called to her bedside, I performed CPR, checking the wall monitor to ensure that my compressions provided the necessary blood pressure. We tried to defibrillate her heart multiple times, all without success. So I continued CPR, waiting for an OR to become available.
Finally, an intern reported the OR was ready. We could take her down right away.
Except I wouldn’t. I wanted a transit monitor — a portable blood pressure monitor that could travel with us as we rolled her through the hall, to the elevator, and down to the operating room — so I could continue to make certain our CPR was adequately maintaining a higher blood pressure to nourish her brain.
Keep in mind that our approach was unusual, even in our own hospital. Very spirited discussions took place, as many staff members wanted to immediately go to the operating room.
“Why are we waiting, Dr. Buckberg? The OR is ready!”
“I’m not moving her until you get a transit monitor up here.”
“She’s dead. We tried to defibrillate her five times — she won’t get better here. Let’s get her into the operating room and work on her heart to fix it!”
But I was not budging. I needed that device to monitor blood pressure. For whatever reason, one wasn’t forthcoming. Meanwhile, residents and nurses kept insisting we immediately head to the OR.
“Listen, I will not go to the operating room to treat her unless I know her brain blood flow is sufficient while we’re transporting her there! If it’s not, she’ll die of brain death, even if I fix the heart. I’ll wait over two hours if I have to!”
As it turned out, we did. Two and a half hours passed — 150 minutes.
The transit monitor finally arrived and we rushed her to the OR where her heart was given controlled reperfusion — and her neurological recovery was excellent.