An exciting future lies ahead.
Link to Helix and Heart video: www.youtube.com/watch?v=R-aPVWOmBjg
CHAPTER 22
Diastolic Dysfunction: Contracting Longer but Not Better
Fifteen million patients in the U.S. and Europe suffer from heart failure. Our RESTORE team addressed this problem in the 50% of patients where the cause was a dilated and stretched ventricular muscle that could not contract properly and ejected poorly — a condition called systolic dysfunction. We showed that a surgical solution to this dilemma was possible for these 7.5 million patients.94 We were frustrated that ventricular restoration was not embraced by the medical community, which failed to accept that it could be used to reverse heart failure in patients with a dilated heart.
At the same time, we were also aware that the other half (7.5 million patients) who develop heart failure — do so despite having a normal ejection fraction. Their hearts have normal size and shape, but cannot fill properly when the ventricle relaxes (diastole) — a condition called diastolic dysfunction. But no one knew why this happened, which meant the key to developing a proper treatment was missing.
Yet I knew that the helix is the centerpiece of the heart, as its two arms determine efficient ventricular ejection and filling. When compromised, it can likewise become inefficient. I believed my new understanding of the helical ventricular band design could serve as the springboard toward discovering fresh insights to counter diastolic dysfunction, which shortens the life of the other half of high-risk heart failure patients.
The “Other 50%”
I began looking for clues.
Patients with diastolic dysfunction develop clinical problems when their lungs become congested. But their complaints of, “I’m having trouble breathing… It’s interfering with my walking… I can’t sleep at night,” similarly occur in patients with failing dilated (stretched) hearts. But diastolic dysfunction patients are different because they have a normal heart size and shape, together with normal ejection fraction (percentage of blood the ventricle pumps into the body). For this reason, the disease is called “Heart Failure with Normal Ejection Fraction” (HFNEF).
While they describe what happens, I knew these words failed to hint at the mechanical cause behind it. Perplexed cardiologists and surgeons echo each other’s lament by asking, “Why can’t they breathe if their heart size, shape, and ejection fraction are normal?”
Without that answer, conventional treatment can only relieve the symptoms of heart failure. Generic medications are given to slow heart rate, relax blood vessels, and decrease heart wall stiffness, while diuretics drain the fluid congesting lungs. Yet the lives of the 7.5 million patients continue to be impacted by this devastating form of heart failure.
As said before, the frequency of congestive heart failure caused by dilated hearts — or from diastolic dysfunction in normal hearts — is comparable (50% in each category). I knew of other similarities, after reviewing data from both forms of heart failure in an outpatient study of 556 patients119 — as each caused the same 16% mortality within six months of treatment, and identically lowered the quality-of-life in survivors.
Yet to my surprise, both types of heart failure are also managed by the same generic treatment (drugs) — even though their failure developed from completely different mechanical causes.
Along with so many other physicians, I too was at a loss for the reasons behind diastolic dysfunction. Yet my motto “disease is a disruption of normality and its treatment must return normality” would continue to guide my efforts to understand diastolic dysfunction — an explanation that had eluded everyone.
Until now.
The Start of a New Search
Colleagues, especially cardiologists, often ask me, “Why does a surgeon study what is essentially a medical issue [that does not strictly aim at solving a surgical dilemma]?”
I am reminded of comments from Dr. Comroe during my training at CVRI (Cardiovascular Research Institute). He would say some outcomes from surgical procedures may generate unique problems — that will stimulate the need to perform new studies to search for their solution. Indeed, my attention became riveted to this issue as I recognized that surgical patients sometimes developed diastolic heart failure after a successful heart operation. I followed my mentor’s suggestion to find out why.
But more than a need to know was compelling me to understand the reasons that heart failure developed in a normal sized and shaped heart. I believed I possessed the tools needed to search out the answer. I could apply my newly acquired knowledge of the helical heart structure and function — to develop novel investigative methods that may finally let us understand this mysterious condition.
A Door Finally Opens
Fortunately, new imaging tools had already opened the way to discovering why hearts with diastolic dysfunction failed. With the development of the echocardiogram, cardiologists by the late 1980s could watch the rate and flow of blood into the heart during its natural sequence of early rapid filling of the ventricle (the interval before it is expelled into the body) — and found that about 70% of the filling occurs during the first third of the diastole (relaxation-filling) phase.120
Those studies were central to exploring the reasons for diastolic dysfunction. They confirmed there was normal ejection during “systole” (when the left ventricle contracts to eject its blood out to the body)… yet identified that the ventricles could not fill properly during their “relaxation” in “diastole” (when the left ventricle fills). Hence the name diastolic dysfunction was coined, and we had our first clue as to what was happening. But still no one knew why.
Or how to counter it.
False Beliefs
The key to developing a proper treatment would grow out of recognizing how this diastolic disease process departs from normal function — since rebuilding normality is the only proper remedy. The starting place must be to understand what determines normal ventricular filling — since ventricular filling was the problem.
It had long been thought the reason that the ventricle fills with blood from the atrium is because of a pressure difference that exists between them. Atrial pressure (pressure in the atrium) is greater than ventricular pressure (pressure in the ventricle). But this explanation seemed unlikely to me, because the pressure difference between the 7 mm Hg atrial pressure and 5 mm Hg ventricular pressure was very slight. It just seemed impossible that this tiny pressure difference would cause the ventricle to receive 70% of its blood during the rapid filling phase that occurs within the first third of diastole.
I believed that suction seemed the most likely cause of filling. After all, the ventricle twists to eject blood during ejection… and then uncoils to suction (or aspirate) blood from the atrium for rapid filling. The dynamics of this suction motion are beautifully evident on magnetic resonance recordings (MRIs). Exploring this movement became the foundation of our new studies to understand why suction occurs — and then to use this knowledge to reverse diastolic dysfunction.
Unrecognized Reality
As I looked deeper into this… the truth began to reveal itself. I reviewed a spectrum of different studies on diastolic dysfunction that had tried to pull together isolated pieces of the puzzle. They showed that the heart size is normal, but for some reason, the heart wall stiffens (could this imply that excess calcium may exist in the ventricle’s wall?).
Most importantly, these studies consistently demonstrated that ventricular suction is impaired.
When faced with such adverse events, our body compensates to keep us alive. Studies showed that when suction is absent, a higher pressure difference is needed to drive blood from the atrium into the ventricle. Atrium pressure rises to 15 to 20 mm Hg or more to stretch this now stiffer ventricular wall (rather than the normal 7 mm Hg atrium vs. 5 mm Hg ventricle difference).
Unfortunately, this is not “a free ride”… because this higher atrium pressure is also transmitted backward into the lungs. This produces their congestion by making fluid fill the
air spaces, which causes the patient to experience shortness of breath. Conventional treatment addresses this symptom of breathlessness, but fails to address why it occurs. …And so it continues.
This failure is due in part to the ongoing belief that the normal heart compresses to eject, but is then followed by passive filling due to a pressure difference between the atrium and the ventricle.
By this point, I was convinced that suction was the key element behind solving this riddle.
New Exploration
My search toward uncovering the answers to this puzzle seemed straightforward, since cardiac performance involves the interaction of only three muscles: the surrounding wrap, and each arm of the helix. Each muscle starts and stops at different times — and the “dominant” one at any given moment determines the heart’s movement104 — since that muscle is contracting most powerfully. It’s like when you move your arm. The biceps and triceps are both contracting, but the arm’s direction is governed by which muscle is strongest during its contraction.
Similar interactions between the helix and wrap occur during each cardiac motion. Therefore, every heart movement we observe can become explained by understanding which muscle is dominant at that given moment.
Heart’s Four-Phase Cycle
There are four phases of motion that occur during every heartbeat. They are:
prepare for ejection
ejection
prepare for suction
suction
Phases one and three have more classical medical names (isovolumic contraction and isovolumic relaxation), but using the phrase “prepare for” may aid your understanding of their roles.
My knowledge of the helical band now allowed me to understand the reasons for each of their movements.
The first phase, “prepare for ejection,” involves contraction of the wrap and the inner arm of the helix to build pressure in the left ventricle (before it ejects blood into the circulatory system). This narrows the ventricle and rotates it counterclockwise. This immediate rise in ventricular pressure also shuts the valves in the atrium so blood does not move backward during ejection. The first part of the classic heart sound of “lub-dub” that everyone knows — the “lub” — is generated during this “prepare for ejection” phase.
The second phase is “ejection.” It happens just 60 ms (milliseconds) later, and begins when the outer helical arm starts to contract. This creates twisting — as the apex (cardiac tip at bottom of heart) rotates counterclockwise while the base (top of the heart) turns clockwise. This movement causes blood to be “wrung” (ejected) from the ventricle, much like wringing a towel expels water.
The third phase is “prepare for suction” — and is what we will chiefly focus upon in this chapter.
This “prepare for suction” phase begins immediately after the ejection stops. It happens as the “dub” (of the “lub-dub”) sound occurs that reflects the closure of heart valves in the aorta (main artery that sends blood into the body) and pulmonary artery (that sends blood to the lungs). During this third phase, the wrap and inner helical arm both stop contracting, but the outer helical arm movement continues. The circumferential wrap unwinds, which triggers a dramatic shift in the heart’s motion: its twisting is abruptly replaced by rapid uncoiling of the whole ventricle (producing a clockwise motion).
A whorl is generated. This whorl creates a centrifugal force that produces a vacuum effect, which occurs as the fourth phase starts and permits suction to begin (as the rapid clockwise motion continues).
Finding the Key
My knowledge of the helical heart allowed me to dive deeper into uncovering the crucial element of why diastolic dysfunction mystery happens: it appeared to be the uncoiling motion, a movement that starts during the “prepare for suction” phase.
This uncoiling happens during the gap of time between the end of contraction by the inner helical arm — and the end of contraction of the outer helical arm. (Figure 1) This interval (that includes the subsequent suction) lasts about 120 ms.
I then realized the key: successful uncoiling will be compromised by any reduction of this time period.
We needed to find out why this would occur.
Which brings us to the fourth phase, “suction,” which rapidly fills the ventricle — and is heavily dependent upon this prior “prepare to suction” interval. Suction only starts when the outer helical arm uncoils — an action that can only begin when it stops contracting.
I finally had my clue.
Figure 1: Experimental evidence of timing sequence of inner and outer helical arm contracting and relaxing, as revealed by sonomicrometer crystals. Outer arm starts after inner arm (shown in left column), and contracts for 90–120 ms more after inner arm stops (shown in right column). LVP = left ventricular pressure, and dP/dT means change in pressure divided by change in time.
The Saga of the Siphon
As I reflected on what I had just discovered… I realized that while diastolic dysfunction describes the ventricle’s inability to properly fill, there has been a glaring failure to recognize that its basic cause is the inability to develop suction. This chasm is in no small part due to the ongoing resistance to recognize that the normal heart must develop suction to fill itself with blood.
Yet such reluctance is surprising because suction is not a new finding.
In AD 180, Galen observed that “the overlying heart, at each diastole, robs the vena cava by violence of considerable quantity of blood.” This action was dynamically apparent as he looked into the chest of a wounded gladiator, to observe the atrium suddenly deflate just after ejection ended — as its blood becomes sucked away to rapidly fill the ventricle. Galen’s introduction of this “ebb and flow” action (that reflected the ventricle sucking in and subsequent ejecting of blood) mirrors the relationship between ocean waves and their undertow.
Galen’s concept remained a common belief for 1,400 years, until Harvey described his theories of circulation in the 1600s. Harvey believed the left ventricle filled due to gravity (the passive process I described where blood transfers due to high atrium pressure and low ventricle pressure). This explanation unfortunately replaced Galen’s concept, and created a misbelief that has persisted for 400 years… until now.
Yet even before now, Harvey’s speculation was not universally accepted, as Gerhard Brecher, a renowned German physiologist, challenged this pressure-related concept in 1956. He declared that the passive ventricular filling explanation was incorrect.121 His experimental studies dramatically documented that the ventricles sucked in fluid themselves. He proved this by connecting a tube from a beating heart to a reservoir placed below the heart, and recording that blood flowed upward into the more highly positioned heart during every beat. The reservoir was below the heart so that pressure could not account for this; suction was the only explanation for rapid filling!
Brecher demonstrated these findings by removing a still-beating heart from a frog and observed it “hop” across a tabletop as it contracted to “eject,” and then “relaxed” to develop suction between beats.
Despite all this, Brecher’s science was not accepted. Physiologists criticized him as they repeated the same condemnations that the “learned critics” had hurled at Galen in the 1600s, when Harvey discovered circulation.
Yet progress inevitably takes place. Some 40 years after Brecher’s denunciation, acknowledgment of suction began to re-emerge as the reason that blood moved rapidly from the atrium into the left ventricle. This was due to the 1996 introduction of three-dimensional MRIs, which affirmed that during its rapid filling phase, the ventricle exerted a vacuum-type effect on blood coming into it from the atrium.
Nature did not change between 1956 (Brecher) and 1996 (MRIs) or between Galen’s AD 180 observation and today. It was our failure to recognize the limitations of our prior investigative imaging tools (2D echo and ventriculograms) that allowed the truth of heart suction to remain camouflaged. Still, most in the medical field continue to pantomime th
e opening and closing of the fist to represent “ejection and suction.” Yet I know that progress is only possible when we can accept the shortcomings of previous beliefs.
Fortunately, the helical ventricular myocardial band provides us with the gift of understanding because it unmasks the reasons for normality, provides new insights into suction’s mechanisms — and possibly reveals ways to combat the ravages of diastolic dysfunction.
Correct Words → Correct Understandings
There is another factor that leads to confusion about heart function.
Proper words to describe the heart’s individual motions are guideposts toward understanding the reasons for diastolic dysfunction. But confusion springs out of the inaccurate vocabulary that exists for describing diastolic dysfunction.
A prime example is the frequently used medical phrase, “isovolumic relaxation interval” (IVR), which describes the 90 ms interval that includes the “prepare for suction” phase between the end of ejection and the start of filling. But “IVR” is not correct, because ultrasonic crystal recordings (the same ones that confirmed the validity of Paco’s model) — demonstrate that the outer arm of the helix does not “relax” during this interval. Instead, it continues to contract.
I realized that the key to comprehending diastolic dysfunction rests on truly understanding what occurs in this vital “prepare for suction” period. Calling this phase “relaxation” is misleading since some of the heart is still contracting. Appreciating this distinction is critical — since the treatment of what goes wrong during this interval is essential to overturning a disease that affects 7.5 million people.
Another deceptive word that hampers this quest is the universally used “untwisting.” The normal heart muscle does not untwist (a movement where the apex would rotate clockwise and the base would rotate counterclockwise). Instead, the whole chamber (apex and base) rotates clockwise during this “prepare for suction” period.
Solving the Mysteries of Heart Disease Page 40
