This chapter is relevant to Section G1(iv) of the 2023 CICM Primary Syllabus, which asks the exam candidate to "describe the normal pressure and flow patterns of the cardiac cycle". Or, it might be more relevant to Section G2(iii), "correlate the mechanical events of the cardiac cycle with the physical, electrical and ionic events". With minimal use of the imagination, one can guess that these curriculum elements basically means "become intimately familiar with every element of a Wiggers diagram". There are two past paper questions which support this view, Question 12 from the first paper of 2018 and Question 21 from the first paper of 2011 which both asked the candidate to "briefly describe the cardiac events that occur during ventricular diastole". Though the examiner comments are very limited (three lines for Question 12), from their content one can establish that a systematic approach to learning about the cardiac cycle would have outfitted the trainees with enough knowledge and structure to pass this question (where only 21% and 8% did, respectively in 2018 and 2011.) Additionally:
In summary, it is impossible to get away without knowing this thing in great detail.
So, what happens in the cardiac cycle, in a nutshell? Literally one thousand things. The college examiners (in 2011, when they still cared) suggest that "one possible way to answer this question is to ... to split the events up for description into mechanical events, ECG events and electrical/ionic events." That's actually really good advice. This chapter will make an attempt to do exactly this, in case it is of any use.
Events during systole:
- Isovolumetric ventricular contraction
- The beginning of this phase corresponds with the peak of the R wave
- This corresponds to Phase 0 (rapid sodium influx) of the ventricular myocyte action potential
- The ventricles begin to contract during this period
- This contraction increases the ventricular chamber pressure and closes the mitral and tricuspid valves.
- As a result, there is a fixed ventricular volume during this contraction
- Early ejection
- The contracting ventricles achieve a pressure high enough to open the aortic and pulmonic valves, and rapidly empty into the systemic and pulmonary circulations.
- This period corresponds to Phase 2 (plateau, rapid calcium influx) of the cardiac myocyte action potential
- On the surface ECG, the end of this phase corresponds to the beginning of the T wave
- Late ejection
- This period begins when ventricular pressure starts to drop, and ends with the closure of the aortic and pulmonic valves
- The end of this period corresponds to the peak of the T wave on the surface ECG
- This corresponds to Phase 3 (repolarisation) of the cardiac myocyte action potential
Events during diastole:
- Isovolumetric relaxation
- The ventricles relax without any change in volume
- The pressure drops until the tricuspid and mitral valves open
- This period corresponds to the end of the T wave on the surface ECG, and the end of Phase 3 of the action potential
- Early rapid diastolic filling
- During this period the relaxing ventricles have pressure lower than atrial pressure, and they fill rapidly
- 80% of the ventricular end-diastolic volume is achieved during this phase
- Coronary blood flow is maximal during this phase
- Late slow diastolic filling
- Ventricular and atrial pressures equilibrate and the atria act as passive conduits for ventricular filling
- The end of this phase corresponds to the end of the P-wave on the surface ECG
- Atrial systole
- The atria contract (right first, then left shortly after)
- This increases the pressure in the ventricles up to the end-diastolic pressure, and adds about 20ml of extra volume to the end-diastolic volume
- These events start at the end of the P-wave on the surface ECG, and finish during the PR interval.
- The end of this phase corresponds to the peak of the R wave, or the Phase 0 (rapid sodium influx) of the ventricular myocyte action potential
As everything else in this chapter is basically a footnote to this item, it is probably reasonable to begin the chapter with a description of what the hell this is, and some example. Basically, a "Wiggers Diagram" is a description of the events which take place over the cardiac cycle and which a plotted on a time scale. Yes, it's the Wiggers diagram, not Wigger's diagram or Wiggers' diagram, because a guy called Wiggers was responsible for the development of its most important components. Occasional variations are tolerated: for example, depending on which textbook you look at, the diagram may or may not contain information about the valve openings, the ionic events, the velocity of blood flow, the heart sounds, and so on and so forth. There is no single "master" diagram in the physiological literature marketplace which might contain all of this information; it is not as if Carl J. Wiggers forged some sort of One Diagram in the fires of Mount Doom. In fact his first attempts to summarise the cardiac cycle into a teachable graphic were published in 1915, and so of course it would not have contained any sophisticated information beyond what could be derived from electrical and pressure recordings.
What did the first Wiggers diagram look like? Even the man unwilling to leave his office chair is able to review the original 1915 publication at archive.org. Out of respect, it is reproduced here with no modification:
That "most recent work" mentioned at the bottom of the diagram is also from Wiggers, published later in a series of two articles in 1921, titled "Studies on the Consecutive Phases of the Cardiac Cycle", where we can see some of his original optical manometer recordings. These tracings were recorded on fast-moving photosensitive bromine paper, speeding across a light beam cast by an electric arc lamp, reflecting from an optical manometer. Some of the original recordings are presented here mainly for historical rather than educational reasons.
This is a simultaneous tracing of the atrial, pulmonary arterial and right ventricular pressures. Note the sawtooth pattern at the bottom. That's a tuning fork vibrating at 50 Hz, to calibrate the speed of the recording. These early pioneers had nothing but manual measurement and chalkboards to support their calculations. Here are the left-sided recordings from the same paper:
As one can plainly see, these recordings' grainy homespun authenticity does not lend any additional value to their educational potential. Subsequent authors took it upon themselves to stylise the superimposed waveforms and expand upon them with (often embellished) volume data, flow curves, electrical phenomena and auscultation findings. An excellent example which contains the kitchen sink can be found in Circulatory System Dynamics by Abraham Noordergraaf (1971, p.10):
Terms such as "systole" and "diastole" need to be defined here, at least in part because the college examiners commented about how "better answers defined diastole" in their response to Question 12 from the first paper of 2018. These are terms which were first used at some stage in the sixteenth or seventeenth century, so we can't really track down and quote the original publication. Moreover, there are numerous different types of definition, based on what is used to measure the phases (ECG, echo, auscultation, etc). Some examples:
Mechanical Systole is the period of cardiac contraction which lasts from the onset of isovolumic contraction to the peak of the ejection phase, so that physiological diastole commences
as the LV pressure starts to fall (Opie, 2005, in a chapter for Braunwald's Heart Disease)
Cardiologic systole is demarcated by the interval between the first and the second heart sounds, lasting from the first heart sound to the closure of the aortic valve. (Yetkin et al, 2013).
Electrocardiographical systole is defined as the period between the peak of the R wave and the end of the T-wave. However, some authors (eg. Brambilla & Margaria, 1966) start systole with the Q wave instead.
The official CICM textbook for cardiovascular physiology (Cardiovascular Physiology, by Pappano and Weir), under the "systole: definition of" index entry, just gives "ventricular contraction" and "ventricular relaxation" (p.2 of the 10th edition). So, there is no real single agreed-upon definition, which makes it somewhat unfair to ask CICM exam candidates to define it in ten minutes during their written exam. Still, one needs to write something, for the marks. Thus, the following arbitrary and unscientific definition is proposed:
If one tries to separate the cardiac cycle into chronological segments, as is the usual custom, one come up against the need to define the boundaries of these segments in some sort of logical non-arbitrary way. This naturally brings up the question: who decided that these were the boundaries, and when did we all agree on this? Again, that was Wiggers. A much later article by Luciado & MacCanon (1971) refers to him extensively wherever the origin of these concepts is alluded to. The main reference would have to be the 1921 paper, "Studies on the consecutive phases of the cardiac cycle: I. The duration of the consecutive phases of the cardiac cycle and the criteria for their precise determination." Modern textbooks don't even quote this paper, much like one does not feel the need to reference the Old Testament when quoting the commandments. In general, seven basic cardiac cycle phases are recognised:
These phases are separated according to mechanical events in the cardiac cycle. A potential eighth phase (identifiable only by echocardiography) might exist between the end of atrial contraction and the closure of the mitral valve, but most physiology textbooks do not mention this. CICM trainees should probably omit it from their answers, as the examiners may have strong opinions regarding this heretical eighth phase.
The waveform used for this was acquired from Nakatani et al (1999). The whole point of that study was to determine whether the LA pressure could be assessed less invasively (i.e. with Doppler echo), but in order to prove this, these guys used a micromanometer-tipped catheter to directly measure the LA pressure in a group of patients who were undergoing cardiac surgery. "After calibrating relative to atmospheric pressure, the catheter was inserted from the right upper pulmonary vein into the LA". As these people were all mechanically ventilated and had diseased hearts by definition (in fact some were undergoing surgery for classical LA-inflating diseases such as MR), one should probably take these measurements with a grain of salt. The original authors' waveform recording was lightly vandalised and a bright red ventricular waveform was superimposed:
Yes, it looks a lot like the CVP waveform, and in fact it is even labelled the same. The sequence of events is:
Most Wiggers diagrams do not include left atrial volume, but perhaps they should, as the change in volume is probably at least as important as the change in pressure. Fortunately, somebody measured this for us - this time with 3D echo and cardiac MRI (Poutanen et al, 2000). Unfortunately, they measured it in children aged 8-13. The volume over time graph below was measured from a nine-year-old boy, which of course means that though the shape of the graph has meaning, the actual volume in mls is much smaller than that of the adult. To scale the volume axis accordingly, data were borrowed from the normal control population in a study of adult TOF patients by Riesenkampff et al (2010). This chimaera was then grafted onto the data from Nakamura et al to produce the hideous mutant below:
To fill in the blanks:
The latter phase is the much-spoken-of "atrial kick", which one loses with atrial fibrillation. How much blood is displaced by this? The total left atrial ejection fraction is usually said to be about 55% (Pellicori et al, 2013), but this is the difference between maximum and minimum atrial volume, and the actual amount of blood displaced by atrial contraction should be much smaller. It is said to be approximately 20% of the end-diastolic LV volume (Namana et al, 2018), or 24 ml for an average LVEDV of 120ml. For reference, normal LA volume ranges (indexed to BSA) are usually 19-41 ml/m2, or 36-77ml for a normal male with a BSA of 1.9 m2 (Aune et al, 2009).
As one might expect, the left ventricle has the highest chamber pressures in the house. Unfortunately, it is usual for pressure waveforms which are measured there to be displayed in a compressed format, which does not lend itself very well to the explanation of events which take place over a few milliseconds (eg. isovolumetric contraction). Moreover, it is hard to find a published LV pressure waveform which is a) at the time scale one requires, and b) not abnormal. The best images one can find without asking for cath lab staff for a favour are actually these, from Curtiss et al (1975).
That loud "hangout" label is due to the authors' focus - the paper was mainly concerned with determining the cause of a split second heart sound. Also, the pressure axis was not labelled in the original publication. That notwithstanding, the pressure recordings are of sufficiently high fidelity that they can be borrowed and used for teaching purposes. In a vain attempt to reduce the corrosion of real physiological data by artistic license, the author initially attempted to stretch and contort the atrial tracing from Nakamura et al to fit these LV waveforms, but that did not work particularly well because the healthy subjects used by Curtiss et al had all sorts of unhelpful normal parameters (like a really low atrial pressure and a really high diastolic pressure). Similarly, though an excellent volume-time curve can be found in Pedrizzetti et al (2003), it just wouldn't fit the diagram. Thus, abandoning all further such efforts, the illustration of left-sided cardiac chamber pressures which is presented here bears no resemblance to any real in vivo measurements, apart from borrowing its vague shape from published recordings.
If a thousand words are more your thing, the cardiac cycle events in the LV are as follows:
Using excellent recordings from Curtiss et al (1975) and Weissel et al (1951), it is possible to construct some composite waveforms to represent the pressures in the right side of the circulation during the cardiac cycle.
In the right atrium, the pressure waveform pattern resembles the familiar CVP waveform, and on average the pressure is a little lower than in the left atrium. These tracings from Weissel et al were laid end-to-end so the reader can appreciate the (trivial but noticeable) pressure difference.
At the same time, Weissel and colleagues recorded the pressure in the rechter Ventrikel in the same patient (a nine-year-old girl with a clinically unimportant ASD):
Obviously, depending on the ventricle, one's experience may differ. Compare with the recording from Curtiss et al:
Though clearly there's some diversity in the exact shape and timing of the waveforms, they do have a certain familiar shape, particularly when one graphs them on a familiar Wiggersian combination plot:
Thus, one can summarise the situation in the right side of the circulation as "everything the same as the left side but at a lower pressure". However, notable differences in timing exist. Here is a grainy scan image of an ancient paper by Braunwalld et al (1956) which presents the simultaneous recording of left and right-sided pressures (from aorta and pulmonary artery):
As you can see, there are some differences in timing between these two sides of the circulation:
If one were to represent these differences visually, one would have to plot the pressure graphs of the right and left sides together, increasing the pixel count and scroll depth of this already interminably long page:
Even though the output of the right side of the heart is by necessity the same as that of the left, the right-sided chamber volumes are different. The end-diastolic right atrial volume is usually slightly larger: 18-50 ml/m2, vs 15-42 ml/m2 for the left atrium (Aune et al, 2009). For the ventricles, Alfakih et al (2003) give 74.4 ml/m2 for the LV, and 78.4 ml/m2 for the RV.
Unlike virtually everything else in this chapter, this specific thing was actually the subject of a past paper SAQ (Question 1 from the first paper of 2009). The trainees were asked to "relate the surface ECG to the events of the cardiac cycle". The college comments were somewhat unsatisfactory, but from what little examiners wrote, one can determine that they were looking for a diagram. Of these, none is better than this one from Braunwald et al (1956):
As one can see, even though the years were unkind to this scanned journal article, the image still has excellent explanatory power. If one needed to somehow reimagine it for the Adobe era, one would probably end up producing something like this:
In the form of verbiage, it could look like this:
Now, that last part is somewhat controversial. In the textbooks, one finds a wide variety of T wave positions in relation to the pressure events in the cardiac cycle. Observe, three different sources with three different positions: the official college textbook, Guyton & Hall, and Kern (from Thoracic Key)
Where does the truth lie? The complex nature of reality here really does not lend itself very well to being described with colourful lines in a textbook, as these diagrams are designed to maximise your understanding of the concepts, not to represent the cardiac cycle with geometric accuracy. Perhaps direct measurements could help, you might think? One might logically expect the original work by Wiggers to be the gold standard for what the Wiggers diagram is supposed to look like, but I do not have a copy of his book, and in any case that was the first decade of the 20th century and he was recording his waveforms with some kind of horrific steampunk apparatus. Those scratchings are probably not to be trusted either. Certainly, you could take a look at some waveforms recorded from real patients in the cath lab. You will find that none of them look like any of the Wiggers diagrams, and what’s worse is they are all different, with different timings. This is because the timing of these events is very dependent on the pressures in the chambers and the aorta. Too much diastolic pressure, and the aortic valve will close early; too little, and it will close later, well after the T wave has subsided. Add LV compliance and LA pressure, and randomness ensues.
In summary, as it is impossible to know the minds of the examiners, the confused trainee is advised to memorise the Wiggers diagram from Pappano & Weir to the point where they can reproduce it faithfully. This exercise should hopefully be protective, because that is the Official Textbook, and so endowed with a sort of Papal infallibility in the CICM exam. The T wave ends before the aortic valve closes, and any other interpretation is apostasy.
The action potential in a cardiac cell is easy to describe and draw, but when one is expected to time the cardiac cycle with these changes, one comes up against the obstacle of logic. Clearly, not all the cells of the myocardium are simultaneously doing the same ionic things. Which cell, then, do you pick to be the ionic standard-bearer for the whole of the myocardium? That's probably why most Wiggers diagrams do not have any "ionic elements" in them. Occasional examples to the contrary do exist. For instance, Epomedicine has an image, clearly scanned from some textbook, but they do not seem to reference any of their borrowed art (including art borrowed from Deranged Physiology). There are a few other examples, mainly from publications dealing with ion channel mutations that give rise to abnormal QT intervals. Basically, it seems that people generally use the ventricular myocyte (specifically, left ventricular myocyte) action potential, because these are the ones responsible for most of the electrical phenomena we record as an ECG; whereas the pacemaker cells and Purkinje fibres are few in number and of minimal importance to the surface ECG.
Using a left ventricular myocyte as The Myocyte, the relationship between the surface ECG and the cellular membrane potential changes would look something like this:
Upon reading this part of Question 23 from the second paper of 2010, the trainees would have probably produced something like this: a Wiggers diagram which plots the action potential of a ventricular myocyte on the same time axis.
However, clearly, that is not what they wanted. Apparently, this part of the question "was best answered using a ventricular pressure-volume loop and overlaying the phases of the ventricular action potential". Where did they get this from? There must be some ancient yellowed first edition of Kam or Guyton & Hall where somebody did this, and that must be where the examiners got their idea from. It is certainly not a natural way to present this information. But, for the purposes of people passing that question in the future, here is just such a loop:
There, that's better. If any reader is able to find a version of this diagram which has any explanatory power, I would be delighted to reproduce it here.
The third edition of the syllabus (CICM, 2017) included "flow patterns (including velocity profiles) of the cardiac cycle" in the syllabus item. It was removed from the syllabus in the 2023 edition, presumably because even the examiners must have found it quite difficult to decipher this fragment of the scrolls because the cryptic phrase "velocity profiles of the cardiac cycle" only appears in search results which originate from CICM or CICM primary exam websites, reverberating around the internet like some weird hooting echo. Surely, a description of flow itself (as in, litres of blood per minute) could not have been the learning objective, as this is uniform throughout the cardiac chambers, and is equal to the cardiac output. Presumably, former members of the Court of Examiners meant something related to Doppler measurements of blood flow velocity which are acquired in the course of an echocardiogram. The ASE Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults (Mitchell et al, 2019) list numerous spectral Doppler measurements (p. 39-45 of the document) which are viewed as essential, and it would be madness to discuss them here, fascinating though they are. Instead, a crude list of normal flow velocities at key regions will be listed here, from a seminal article by Wilson et al (1985):
|Modal peak velocity in cm/sec,
as range (mean)