29, November 2022 by Shahriar Lahouti.

CONTENTS

• Preface
• Case scenario
• Pathophysiology 
• Predisposing factors
  • Vicious spirals of dynamic LVOTO
• Etiology
• Clinical presentation
• Echocardiography
  • 2D echo
  • Doppler echo
• Principles of management
• Media
• Going further
• References

Preface

Left ventricular outflow tract obstruction (LVOTO) is the third most frequent cause of unexplained hypotension, and it should be considered in any hypotensive critically ill patients *. The current trend to treat hypotension in critical setting is to place a greater emphasis on inotropes and vasopressor support and less on fluid resuscitation in order to limit the potential harm from fluid overload. This combination may trigger LVOTO in susceptible patients. In fact, LVOTO will often respond to various interventions in the opposite fashion than might be expected for most patients in shock state. It has been shown that dynamic LVOTO has been frequently underdiagnosed in critical care setting *. Unrecognized LVOTO may lead to a spiral of inappropriate vasopressor/inotropic use resulting in severe hypotension, collapse and death.

Case scenario

A 69-year-old obese man with a history of hypertension, diabetes and stage III chronic kidney disease was admitted to the hospital for urosepsis. Two days into his admission, he was found to be unresponsive, with a heart rate of 122 bpm, and a blood pressure of 60/35 mm Hg. He rapidly progressed to pulseless electrical activity (PEA). CPR was performed with return of spontaneous circulation. He was emergently intubated and norepinephrine was started with dose escalation rapidly over the next hour due to continued hypotension.

• Bedside echo: a small, underfilled, hyperdynamic left ventricle, but no evidence of RV strain. 
• Lung ultrasound: Bilateral diffuse B-lines.
• IVC: poor window.

👉How you will evaluate the refractory shock in critical patients? (see here)

Pathophysiology of LVOT obstruction

In patients with small left ventricular chamber size (e.g. due to hypertrophy), LV outflow tract is narrowed and the blood flowing through this narrowed segment has a high velocity. Fast-flowing blood through the LV outflow tract will pull the mitral valve leaflets toward the septum (anteriorly) due to the Venturi effect * . This is known as as Systolic Anterior Motion (SAM) of the mitral valve and contributes to dynamic obstruction of LVOT.

• SAM is defined as the anterior excursion of one or both mitral valve leaflets into the LVOT during systole (figure below).
• This has two hemodynamic consequences:
  • Left Ventricular Outflow Tract Obstruction (LVOTO): Anterior motion of mitral valve during systole, can cause an obstruction of the LV outflow tract. This will impair systolic ejection of the blood into the aorta and will reduce cardiac output; which can potentially cause cardiogenic shock.
  • Mitral Regurgitation (MR): The “systolic anterior motion of mitral valve” causes mitral regurgitation as the mitral valve is opened during systole.
    • Opening of mitral valve leaflets (due to “SAM” of leaflets) will cause a posteriorly directed mitral regurgitation (MR).
    • MR will cause elevated left atrial pressure and can contribute to cardiogenic pulmonary edema.

Predisposing factors

Dynamic LVOTO is more common in the elderly, females, and in patients with hypertension, diabetes, and chronic vascular disease. This results from the interplay of multiple factors including anatomic and physiologic conditions *.

Anatomic predisposing factors

• Left ventricular hypertrophy (esp. anterobasal hypertrophy), small left ventricle size, sigmoid septum.
• Elongated/floppy mitral valve leaflets *.
• A combination of apical hypokinesis and hypercontractility of the base of the heart will predispose for generation of dynamic LVOTO. This condtion can be seen in patients with classic form of takotsubo cardiomyopathy and LAD artery ischemia (see below).

Physiologic predisposing factors

• Generally, LVOTO is a dynamic phenomenon and varies according to the loading conditions. Any factors that can cause the left ventricle to be hyperkinetic and underfilled (thereby increasing the velocity of blood ejected through the LV outflow tract and reducing the end-systolic chamber size) can perpetuate LVOTO.
• Factors which increase LVOTO include *
  • ↓Preload: Anemia, dehydration, sepsis (relative hypovolemia), diuretics, vasodilators e.g. nitrates.
  • ↓Afterload: vasodilators, sepsis, some anesthetic medications.
  • ↑LV inotropy (contractility): High endogenous sympathetic tone, exogenous inotropes *.
  • Tachycardia (reduced diastolic filling time).

Vicious spirals of dynamic LVOTO

Dynamic LVOTO once established can cause deteriorating hemodynamic status to pulseless electrical activity.

• If unrecognized, high dose of vasopressor use in patients with (resistant) shock, can lead to worsening hemodynamics.
• Vasopressors and inotropes make the left ventricle to be hyperkinetic and underfilled (esp. in the presence of hypovolemia), thereby increasing the velocity of blood ejected through the LVOT and reducing the end-systolic chamber size).
• Worsening LVOTO severity promotes further hemodynamics derangement leading to pulseless electrical activity and cardiac arrest.

Etiology 

LVOTO has been classically described in patients with hypertrophic cardiomyopathy, however it has been reported in other conditions.

• Hypertensive cardiomyopathy *
  • Chronic hypertension may cause hypertrophy of the left ventricle and septum *.
  • LVOTO is particularly common in elderly patients with a “sigmoid septum,” which is more prominent hypertrophy of the basal septum (aka. basal septal hypertrophy; “BSH”; figure 1 below) *, *.
• Hypertrophic cardiomyopathy (HCM)
  • Dynamic LVOTO is typically observed in the setting of hypertrophic cardiomyopathy *.
    • Approximately one third of patients with HCM have LVOT obstruction at rest.
    • One third of patients have provokable obstruction via maneuvers that change loading conditions (e.g. amyl nitrite, dobutamine, or the Valsalva maneuver *).
    • The remaining third have left ventricular hypertrophy with neither baseline nor provokable obstruction *,*.
• Takotsubo cardiomyopathy (TTC)
  • LVOTO can occur in the classic form of takotsubo cardiomyopathy with apical hypokinesis (apical ballooning) and hypercontractility of the base of the heart (figure 2 below) *,*.
    • Apical hypokinesis causes septal angulation which, combined with basal hyperkinesis, causes LVOTO .
  • Takotsubo cardiomyopathy is complicated by LVOTO in approximately 20% of cases *,*.  Associated risk factors include:
    
    • Older age, septal bulging, SAM-induced mitral regurgitation and hemodynamic instability.
• Left anterior descending (LAD) coronary artery ischemia with apical hypokinesis
  
  • This will produce a substrate similar to takotsubo cardiomyopathy with apical hypokinesis and hypercontractility of the heart base (figure 2 below) *, which in combination can cause LVOTO *,*.
• Distributive shock with volume depletion
  • A combination of profuse vasodilation and high sympathetic tone can cause dynamic LVOTO *,*, especially in patients with septic shock *.

Clinical presentation

• Syncope, dyspnea, hypotension and cardiogenic shock.
• Cardiac arrest {pulseless electrical activity (PEA)}
• Vasopressor refractory shock
  • Inotropes increase the velocity of the blood flow through the LVOT, which will worsen the anterior mitral motion.
• Diuretic refractory cardiogenic pulmonary edema (CPE)
  
  • Diuresis reduces the diastolic volume of the left ventricle. This moves the mitral valve closer to the LVOT, worsening obstruction.

Echocardiography

Diagnosis of dynamic LVOTO should be suspected in appropriate clinical setting. Bedside echo plays an essential role in confirming the diagnosis and excluding other possibilities of hemodynamic deterioration in critical patients.

2D echo findings

• Left ventricular hypertrophy with small chamber size.
• Hyperkinetic LV with near obliteration of the left ventricular cavity during systole (i.e. a pathologically elevated ejection fraction). More on estimating LV EF here.
• Mitral regurgitation (MR) is generally present, typically directed into posterolateral left atrium.
  • In contrast to posteriorly directed MR, the presence of a central or anteriorly directed MR jet suggests the presence of intrinsic mitral valve disease.
• Systolic anterior motion of the mitral valve
  • During systole, the mitral valve leaflets are tugged towards the septum (video clip below).
    • M-mode parasternal long axis echo can confirm the LVOT obstruction (figure 3 below). 

Parasternal long-axis view: a small, underfilled, hyperdynamic left ventricle with systolic anterior motion (SAM) of the anterior mitral valve leaflet into the left ventricle outflow tract (LVOT) during systole (a zoom-in view shows the “SAM” of the anterior mitral valve leaflet).

• Takotsubo pattern (apical dilation with basal hyperkinesis, shown below).

Doppler echo findings

• The hallmark of dynamic LVOTO is a high-velocity, late-peaking continuous-wave Doppler signal on echocardiographic examination through the LV outflow tract (described as “dagger-shaped”). See figure 4 below.
  
  • The late-peaking nature may help differentiate this from aortic stenosis, which increases velocity with a more symmetric appearance.
• The maximal pressure gradient can be calculated based on the modified Bernoulli equation (∆P = 4V²).
  • LVOT gradient >30 mm Hg (2.7 m/s) is considered pathologically elevated *.
  • LVOT gradient >50 mm Hg (3.5 m/s) is severely elevated.

Principles of management

⚠️Medication/intervention to avoid

• Vasodilators: Dihydropyridine calcium channel blockers (e.g. amlodipine), nitrates, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers *.
  
  • These can produce a fall in peripheral resistance with an increase in LVOTO and filling pressures, thereby resulting in hypotension and/or worsening of heart failure symptoms.
• Inotropes: Dobutamine, epinephrine 
  
• Diuretics
  • By reducing preload, diuretics can result in reduced LV filling, a smaller LV chamber, and therefore greater LVOT obstruction.
• Intra-aortic balloon pump (which reduces afterload).

Management of  LVOTO in patients with hypotension/ cardiogenic shock

• Pure vasoconstrictors (phenylephrine, vasopressin)*
  • Vasoconstriction reduces LVOTO via several mechanisms, including: ↑afterload, ↑preload, and a mild reflexive bradycardia, which improves ventricular filling and increases ventricular volume.
  • Phenylephrine may selectively improve vascular tone and reduce LVOTO *. It is more convenient, since it has a shorter half-life, allowing it to be more titratable.
    
    • Norepinephrine primarily functions as a vasoconstrictor, so it shouldn’t be a strong inducer of LVOTO. However, case reports describe norepinephrine causing LVOTO *.
• Fluid administration: For patients who are hypovolemic, fluid resuscitation will improve preload and ventricular filling.
  • Using vasopressors before addressing intravascular volume deficits in critically ill patients can increase contractility in a volume-depleted and small left ventricle, stimulating the onset of LVOT obstruction.
• Beta blockers
  • Beta-blockers may decrease LVOTO, thereby improving cardiac output and blood pressure by several mechanisms including: ↓heart rates (permitting improved LV filling) and a negative inotropic effect both of which alleviate LVOTO.
  • In hemodynamically unstable patients, it may be safest to use a short acting agent e.g. an esmolol infusion, with gradual uptitration and careful monitoring of hemodynamic effects *.

Case revisited

In patients with refractory shock, evaluation should focus on the identification of the primary cause and reversible secondary contributors, such as hypovolemia, pump failure, or obstruction that is causing shock *. (This will be discussed separately in detail). Bedside echo is an essential tool to assess fluid status, ventricular ejection fraction, or any other myocardial complications.

• In this case, LVOTO was confirmed using M-mode in parasternal long axis view.
• Patient hemodynamics stabilized following discontinuation of norepinephrine, initiation of vasopressin and esmolol infusion.   

Media

Further going

• Transient ‘SAM’ of the Mitral Valve Leaflet in a Critical Care Patient with a Structurally Normal Heart 

• Dynamic left ventricular outflow tract obstruction (IBCC)

References