Though left ventricular outflow tract obstruction is usually a dynamic phenomenon which could happen to any ICU patient, this chapter has been thrown into the Cardiothoracic ICU section mainly because of completely irrational personal reasons, i.e. that's the sort of place where the author encounters it most frequently, usually in patients waiting for or recovering from cardiac surgery. It could just as easily belong in the cardiology section.
The topic of LVOT obstruction had appeared in Question 8 from the first paper of 2019, where quite a significant amount of detail was asked about. In terms of published peer-reviewed information about this disease process, Vilcant & Hai (2018) have an excellent free introduction, though without very much detail on management. Sen-Choudhry et al (2016) is where you would go for the management details, but it is unfortunately paywalled by Nature. The salient features of management from this article are summarised below. Additionally, a free article by Poliac et al (2006) gives some excellent pragmatic recommendations regarding the haemodynamic management of the obstruction-prone LVOT during anaesthesia. The wording of the college answer to Question 8 suggests that it was written after reading Slama et al (2016), but the article does not contain anything additive beyond the already quoted resources, and one does not need to pay for it.
Predisposing conditions for LVOT obstruction
- Concentric LV hypertrophy
- Eccentric septal hypertrophy
- Systolic anterior motion of the mitral valve (SAM)
- Structural causes of anterior mitral valve leaflet or apparatus position
- Redundant anterior leaflet
- Redundant posterior leaflet
- Papillary muscle displacement
- Prosthetic valve placement
- Infiltrative cardiac disease
- Cardiac amyloid
- Fabry disease
- Danon disease
- Friedrich ataxia
- Cardiac oxalosis
Precipitating factors of LVOT obstruction
- Insufficient diastolic filling pressure
- Atrial fibrillation
- Insufficient diastolic filling time
- SVT or VT
- Insufficient afterload
- Vasodilation due to sepsis
- Vasodilator drugs, eg. nitrates or general anaesthetics
- Excessive contractility
- Inotrope drugs
Clinical features include:
- Haemodynamic instability associated with stress
- Ejection systolic murmur, louder with Valsalva (whereas AS becomes softer)
- MR murmur
- Brockenbrough–Braunwald-Morrow phenomenon: "a paradoxical decrease in the arterial pulse pressure and an associated increase in the LV systolic pressure in the beat following a PVC" (Trevino & Buergler, 2014).
- Brisk arterial pulse with rapid systolic rise and rapid drop-off
- Characteristic "spike and dome" appearance of the aortic pressure trace
Management consists of targeting the following parameters:
- Preload: keep it high-normal.
- Rate: keep it slow.
- Rhythm: keep it sinus.
- Contractility: bring it down. Negative inotropes are often called for, eg. beta-blockers
- Afterload: keep it high. Use vasopressors with minimal beta effect (eg. vasopressin or phenylephrine)
Robert Walmsley's 1979 review article is probably the most useful thing to read if one is trying to figure out what this thing is form an anatomical perspective. It is basically a muscular tube which is continuous with the left ventricular cavity. There is of course no specific defining structure which could be used to functionally define where the LV chamber ends and the LVOT begins, and so we arbitrarily define the outflow tract as "that part of the left ventricular chamber that lies in front of the anterior cusp of the mitral valve".
The length of this tract in adults is about 25mm. The anterior wall of the outflow tract is formed by the ventricular septum, and the posterior wall is formed by the anterior cusp of the mitral valve. For the purposes of measuring the LVOT VTI by pulse wave Doppler, this thing is usually assumed to be cylindrical during systole (though it assumes an ovoid shape as it relaxes). The cross-section indexed to body surface area is around 2.3cm2/m2 for females and 3,6cm2/m2 for males (Halpern et al, 2012). These numbers have some meaningful significance, because of the fact that the entire cardiac output passes through this muscular tube on its way out of the left ventricle. As such, the crossectional area of the LVOT can be used in combination with a measured VTI (velocity-time integral) to calculate the stroke volume, and therefore cardiac output.
Obstruction of the LVOT is something which can occur dynamically during systole, usually requiring the coexistence of some physiological change and some predisposing anatomic factors. Fixed LVOT obstruction is the logical opposite of the normal "dynamic" obstruction. Conceivably, LVOT obstruction could also occur statically, i.e. the obstruction may be present during systole and diastole. Strictly speaking, aortic stenosis and coarctation of the aorta are both examples of fixed obstruction, though neither of them involves the anatomical LVOT. If we are talking about a fixed obstruction, several possibilities arise, discussed in the article by Vilcant & Hai (2018):
Obviously, these conditions will all have different haemodynamic characteristics as compared to dynamic LVOT obstruction. The pixellated graphs below are from Hong et al (2016), who measured these things directly. In short, in fixed subaortic obstruction, the obstruction starts with the aortic valve opening and continues throughout systole, whereas in dynamic LVOT obstruction the aortic pressure is initially normal and falls only in late systole, producing a characteristic "spike and dome" appearance.
Of course, that's not even remotely relevant to the CICM Fellowship exam candidate, because the college did not want any of this information in their question on dynamic LVOT obstruction.
Anyway. Structural problems which lead to LVOT obstruction include the following:
Hypertrophic obstructive cardiomyopathy (HOCM) is, of course, one of the causes, as is produces a thickening of the left ventricle. When Kobayashi et al (2017) sampled patients with an increased LVOT pressure gradient, they found that the obstruction was due to HOCM in 74% of them, with vanilla LV hypertrophy present in only 9%. HOCM is an autosomal dominant genetically transmitted disorder and the most common genetic cardiomyopathy.
Left ventricular hypertrophy: the symmetrical thickening of the entire myocardium is a completely stereotypical and unimaginative kneejerk reaction to increased afterload by the boring predictable left ventricle. When the going gets tough, the tough get thicker and less compliant. This is distinct from HOCM because it is reversible. To quote a review article by Pennacchinni et al (2015),
"LVH in patients with HCM is caused by mutations in sarcomere genes and is not reversible. Conversely, LVH in hypertensive patients is secondary to increased afterload and may regress during antihypertensive treatment"
There is, of course, a significant minority of patients whose hypertensive LVH is so significant that they satisfy HOCM range of echocardiographic and ECG criteria. Furthermore, the pragmatic intensivist might rightly complain that we rarely spend enough time with our patients to make a diagnosis on the basis of their response to months of treatment. Fortunately, for the purposes of this chapter, the distinction between HCOM and LVH is quite meaningless, as both are likely to produce LVOT obstruction by essentially the same mechanism.
Asymmetric septal hypertrophy: instead of the whole left ventricle, just the interventricular septum may thicken hideously because of some disease process. The abnormally muscular septal wall segment ends up being a huge mutant lump in the LVOT, obstructing it in end-systole. Eccentric hypertrophy like this may be a feature of early HOCM; late in HOCM the whole ventricle is hypertrophied but the septum is especially so, as seen below.
Obviously, HOCM is the most common cause of basal septal hypertrophy, but apart from that it can also develop as a consequence of any afterload-increasing condition, just like LVH. Why does the basal septum hypertrophy like this in some people but not in others? This is not clear. Kelshiker et al (2013) suggest that the basal septum has some sort of unique properties which make it susceptible to the hypertrophy-inducing afterload stimuli associated with hypertension and aortic stenosis.
SAM: In systole, the walls of the LV come together, and the anterior mitral valve leaflet may move anteriorly. The latter is called SAM ("Systolic Anterior Motion"). This is always abnormal: that leaflet is not supposed to do that in a normal heart during routine use. Though originally in the 1960s it was thought to be a pathognomonic feature of HOCM, it can actually occur in all sorts of conditions which are unrelated to HOCM: Ibrahim et al (2012) summarise these rather well in their "Figure 1". In short:
The onset of some of these factors, rather congenital or chronic and gradual, may be acquired rapidly following mitral valve replacement. A "high-profile" prosthetic valve, or one which is not properly oriented, may cause LVOT obstruction shortly after MVR (Guler et al, 2006); the act of seating the valve may change the dimensions of the LV chamber. For this reason (one might assume) the college included MVR as one of the predisposing factors in their answer to Question 8 from the first paper of 2019.
Infiltrative cardiac disease: cardiac hypertrophy can develop as a consequence of some insidious impostor which penetrates the myocardium and replaces or displaces its tissues. The resulting ventricle is often sufficiently hypertrophied to predispose a person to LVOT obstruction. A good review article by Seward et al (2010) lists several pathologies which may give rise to this:
It would make sense to expect that some functional factor would have to be present to cause LVOT obstruction because there's plenty of people out there in the community with severe LVH, and clearly they are not all walking around with constantly obstructed LVOTs. Indeed there are several characteristic elements which exacerbate or promote LV outflow tract obstruction to the point of causing haemodynamic compromise. With enough of these factors in play, even a structurally normal heart can develop LVOT obstruction. For example, by volume-depleting a hypertensive patient and poisoning them with dobutamine, Yang et al (2008) were able to generate a very convincing LVOT obstruction picture in somebody with a relatively normal heart at baseline.
Insufficient diastolic filling pressure: a large end-diastolic chamber volume is a relatively good protector of LVOT patency. Empty the ventricle, and the thickened walls are more likely to come together, blocking the LVOT and creating haemodynamic havoc. As such, these people are generally quite sensitive to the loss of fluid. The data for this mainly comes from ancient studies, performed during times of diminished ethical scrutiny. For example, Shah et al (1965) were able to convince two women and four men with HOCM to undergo a 500ml phlebotomy and discovered that their cardiac output fell by up to 60%. At the same time the LVOT pressure gradients increased, suggesting that the LVOT was becoming more narrow (and therefore generating higher pressure gradients).
Insufficient diastolic filling time: Isovolemic relaxation of the huge hypertrophied ventricle is prolonged; it takes time for it to relax enough for a decent end-diastolic volume to accumulate, irrespective of the diastolic filling pressure. Sanderson et al (1977) explored this with angiography and found an abnormal filling pattern, partly due to the abnormal cavity shape of the ventricle. The upshot of this is that the effect of tachycardia will be haemodynamic instability and probably pulmonary oedema.
Insufficient afterload: raised aortic pressure counteracts the raised LV pressure and "splints" the LVOT open during systole, decreasing the chance that the outflow tract will collapse in the middle of it. Hadjimiltiades et al (1991) tested this hypothesis by challenging some HOCM patients with archaic recreational nitrates. "While recording continuously, an amyl nitrite capsule was crushed and the patient was instructed to inhale deeply and slowly three times", the authors gloat. The LVOT peak velocities spiked massively in response to the systemic arterial vasodilation. This effect was so profound and so reliably reproducible that it could be used to noninvasively make the diagnosis of hypertrophic cardiomyopathy, the authors concluded. That this effect can be demonstrated independently of beta-blocker or calcium channel blocker therapy suggests that afterload may be the most important haemodynamic parameter in HOCM management and prevention of LVOT obstruction. No matter how you lower their heart rate or manipulate their preload, they will still obstruct when their afterload is low.
This is also interesting because there are some scenarios where the intensivist or anaesthetist may find themselves managing a patient in whom afterload has been purposefully decreased, and who has now developed a predilection for LVOT obstruction. Classically, this is seen in aortic valve surgery, where after years of hypertrophy and high afterload the ventricle now finds itself contracting against a substantially lower backpressure. The resulting loss of afterload produces dynamic LVOT obstruction in patients who return from the operating theatre following aortic valve replacement (Panduranga et al, 2010) or TAVI ( Tsuruta et al, 2018).
Excessive contractility: Where one's LVOT wall is especially muscular and prone to obstructing itself in the process of contraction, it would be logical to expect that obstruction to worsen whenever anything is administered which might increase the force of that contraction. That would be just about any inotrope, or heightened levels of stress, for example. anxiety, pain, shortness of breath, and so on. This has been demonstrated in some cruel animal experiments by Cross & Salisbury (1963). "Seventeen of the 23 animals had been subjected to a bilateral thoracotomy in the fourth intercostal space... the venae cavae were ligated, and the entire systemic venous return was diverted to an extracorporeal reservoir by large plastic tubes that had been inserted through a femoral and jugular vein". Classic features of obstruction were then demonstrated in animals who received isoprenaline.
Arrhythmia, particularly tachyarrhythmia, predispose to LVOT obstruction mainly by shortening the diastolic time and (in the case of AF) by robbing the LV of a much-needed atrial filling "kick" during diastole.
As it is probably the single most important portion of the systemic arterial circuit, one might imagine the obstruction of the left ventricular outflow tract would have some important haemodynamic consequences. In the literature, case reports of this condition usually use words like "cardiovascular collapse" to describe them.
Left ventricular outflow tract obstruction (due to SAM) leads to the extension of the systolic ejection phase and a decrease in ejection volume. It can also lead to coaptation of mitral leaflets and, as a result, to significant mitral insufficiency, which further impairs cardiac output
Haemodynamic instability associated with stress is a cardinal feature. The classical feature is a worsening cardiac output and poorer blood pressure associated with situations which would generally be associated with a high cardiac output, such as sepsis, liver failure, stress, pain, etc. The patient falls apart haemodynamically at the most inopportune moments.
Ejection systolic murmur can often be heard, which usually sounds a lot like the murmur of aortic stenosis, except it gets louder with Valsalva (and it is virtually the only murmur that does that). It usually does not radiate to the carotids, and it tends to vary with prevailing haemodynamic conditions (i.e. it can disappear entirely if the dynamic LVOT obstruction is relieved).
Mitral regurgitation and features of LV failure often tend to develop as a consequence of poor cardiac output and increased left ventricular systolic pressure. The mitral valve ends up being the "blow off" valve for the raised intraventricular pressure, and the left atrium receives the overflow of blood which does not get ejected during systole. Enlarged atria with a propensity to fibrillation are usually the result of this sort of thing going on chronically.
The Brockenbrough–Braunwald-Morrow phenomenon is a classic haemodynamic trick which involves waveform interpretation and invasive measurement, always a favourite combination for the cardiothoracic intensivist. It was discovered by the eponymists in 1961, when they promoted it as a diagnostic technique to identify HOCM. The demonstration of this phenomenon requires "a paradoxical decrease in the arterial pulse pressure and an associated increase in the LV systolic pressure in the beat following a PVC" (Trevino & Buergler, 2014).
This haemodynamic tracings image was stolen shamelessly from the original paper and gently molested with Illustrator (note how the date in the corner of the image is June 12th, 1959). Basically, the longer time between the PVC and the next systole leads to an increase in left ventricular filling, which in turn results in an increased contractility (by the Frank-Starling relationship). The increased contractility leads to obstruction, because HOCM. Thus, the next heartbeat obstructs itself, the LV pressure ends up being massive, and the arterial pressure ends up compromised because the LV outflow tract prematurely closes.
Characteristic findings on palpation of the pulse, or on inspection of the arterial trace: Though nobody seems to feel for pulse anomalies any more, some people may still scrutinise the shape of the arterial pulse, as this is made conveniently available far from the bedside by the screens of monitoring equipment. In case one ever actually lays hands on the patient, one might discover that - though there is a systolic murmur sounding like aortic stenosis - the arterial pulse will be brisk, with a rapid systolic rise. There will usually be a sudden steep decline in mid-systole. The following illustrative tracings were acquired by Goodwin et al (1960) who, in reporting this condition, first used the term "obstructive cardiomyopathy".
The approach to keeping these patients stable can be summarised as "keep 'em wet and slow". As with all things haemodynamic, this can be broken down to basic haemodynamic parameters suceptible to our manipulation:
Preload: keep it high-normal. Insufficient diastolic filling pressure is said to contribute to LVOT obstruction. So, that probably suggests that you should give these people some filling. However, determining exactly how much filling is required remains the province of chance. Evidence (Chan et al, 1990) suggests that free-range HOCM patients generally tend to operate at the flat part of the Frank-Starling curve, because filling them up with a modest amount of fluid in the laboratory did not seem to change their cardiac output. Ergo, added filling beyond euvolemia will probably not achieve the haemodynamic outcome you desire, and may produce some embarrassing pulmonary oedema.
Rate: keep it slow. The demonstrated relationship between tachycardia, LVOT obstruction and haemodynamic compromise would suggest that these people function optimally at some slower heart rate. Given that their stroke volumes are relatively fixed, the heart rate should also not be too slow. Though one might object that the terms not too slow and fast enough are not exactly scientific, the pragmatic intensivist would remark that the rate to aim for is going to be relatively individual and best determined by trial and error at the bedside. One might assume the resting pre-admission heart rate is the optimal one, given that the patient presumably felt well with it. No textbooks or article is brave enough to recommend an actual value for the heart rate.
Rhythm: keep it sinus. AF disturbs the haemodynamic applecart by being rapid and by failing to contribute a much-needed volume boost to the tiny LV chamber. Irrespective of rate, AF may be the difference between stability and instability in this group of patients.
Contractility: bring it down. Negative inotropes are often called for, and positive inotropes are generally viewed as counterproductive. The experimental animals used by Cross & Salisbury (1963) inevitably developed LVOT obstruction when isoprenaline was used to drive their cardiac output, something which was only relieved by the opening of their pericardia, or by a significant increase in preload. Sherrid et al (1998) demonstrated that negative inotropes (in that case, 15mg of intravenous metoprolol) "decrease LV ejection acceleration and thereby eliminate mitral-septal contact and obstruction".
Afterload: keep it high. Diastolic pressure should be kept high, in order for the beefy LV to get some proper coronary perfusion. but beyond that afterload appears to be a very important component of maintaining LVOT patency during systole. As demonstrated by Hadjimiltiades et al (1991), the sudden loss of afterload following amyl nitrate administration dropped the cardiac output by half, and caused some of their HOCM volunteers to faint.