Norepinephrine-associated left ventricular outflow tract obstruction and systolic anterior movement

Abstract

In the perioperative setting, norepinephrine is used to increase blood pressure, an effect mediated mostly via arterial and venous vasoconstriction. Thus, norepinephrine is, allegedly, less likely to cause or worsen left ventricular outflow tract obstruction (LVOTO) than other inotropes. We report a case of norepinephrine-associated dynamic LVOTO and systolic anterior movement in a predisposed patient. This report highlights that unrecognised dynamic LVOTO may worsen shock parameters in patients treated with norepinephrine who have underlying myocardial hypertrophy.

Background

Left ventricular outflow tract obstruction (LVOTO) with or without systolic anterior movement (SAM) of the mitral valve following aortic valve replacement is associated with increased mortality.¹ In a predisposed patient with septal hypertrophy, precipitating factors include hypovolemia due to perioperative blood loss and capillary leak, tachycardia and inotropic stimulation due to pain or medications. A high index of suspicion may allow early recognition and implementation of corrective measures such as fluid loading, avoidance of inotropic and chronotropic stimulation, administration of pure vasoconstrictors. In the perioperative setting, dobutamine has been identified as an important precipitating or exacerbating factor.^{2 3} In contrast to dobutamine, norepinephrine activates both alpha1 and beta1 adrenergic receptors.⁴ As such, it increases heart rate and myocardial contractility,⁵ while also causing arterial and venous vasoconstrictor mediating an increase in afterload and preload.⁶ Thus, norepinephrine is, allegedly, less likely to cause or worsen LVOTO providing clinicians a false sense of reassurance. We report a case of norepinephrine-associated dynamic LVOTO and SAM.

Case presentation

An 80-year-old male patient with a critically stenotic bicuspid aortic valve was admitted for elective bioprosthetic aortic valve replacement.

His most recent transthoracic echocardiography showed a bicuspid valve with 76 mm Hg (peak) and 45 mm Hg (mean) gradients as well as a non-indexed aortic valve area of 0.75 cm² and a Vti1/Vti2 ratio of 0.21. The left ventricular ejection fraction of 65% and intraventricular gradients of 4 mm Hg (rest) and 22 mm Hg (Valsalva) were not associated to a SAM of the mitral valve. The rest of the exam was within normal limits.

Following the implantation of a MagnaEase #25 bioprosthesis under extracorporeal circulation and cardioplegia, the patient was difficult to wean from the extracorporeal circuit. A transesophageal echocardiography revealed a severe aortic insufficiency involving the entire left coronary cusp and the left–right coronary commissure. The aortotomy was reopened and the coronary cusp repaired by suturing the prosthesis’s skirt at the left coronary cusp. A subsequent transesophageal echocardiography confirmed that the bioprosthesis was functional, and the patient was removed from the extracorporeal circuit before being transferred to the intensive care unit.

Investigations

On arrival in the intensive care unit, the patient was in pulmonary oedema and severely hypotensive. The norepinephrine infusion initiated in the operating room was rapidly increased from 2.66 to 64 µg/min in order to maintain a mean arterial blood pressure of 65 mm Hg, as prescribed. Although the patient was not tachycardic (87 beats/min), a transesophageal echocardiography revealed a functional aortic bioprosthesis with a left ventricular ejection fraction of 80%, a peak intraventricular gradient of 53 mm Hg (figure 1) and SAM causing severe mitral regurgitation.

Figure 1.

Left ventricular outflow tract before discontinuation of norepinephrine. (A) Colour Doppler transesophageal echocardiography—transgastric 5-chamber view showing aliasing and severe mitral regurgitation, (B) Continuous Doppler signal demonstrating dynamic obstruction with a left ventricular-aorta gradient of 53 mm Hg.

With the transesophageal echocardiography probe in place, the norepinephrine dose-rate was rapidly decreased to 8 µg/min and phenylephrine was started and increased to 133 µg/min to maintain mean arterial blood pressure values of at least 70 mm Hg. Vasopressin (constant dose rate of 0.04 units/min) and 500 mL of albumin 5% were also administered concomitantly. The next transesophageal echocardiography showed a decrease of the heart rate (72 beats/min), a decrease of the peak intraventricular gradient to 26 mm Hg (figure 2) and the improvement of SAM of the mitral valve leaflet (videos 1 and 2). Following these interventions, the patient's condition stabilised.

Figure 2.

Left ventricular outflow tract after discontinuation of norepinephrine. (A) Colour Doppler transesophageal echocardiography—transgastric 5-chamber view demonstrating reduction of severe mitral regurgitation to mild, (B) Continuous flow Doppler signal demonstrating a reduction of dynamic obstruction with a left ventricular-aorta peak gradient of 26 mm Hg.

Video 1.

Download video file ^{(136.5KB, mp4)}

DOI: 10.1136/bcr-2018-225879.video01

Video 2.

Download video file ^{(441.2KB, mp4)}

DOI: 10.1136/bcr-2018-225879.video02

Differential diagnosis

Dynamic LVOTO has been described in the context of congenital hypertrophic cardiomyopathy, acute myocardial infarction with apical–septal akinesia, reduction of the angle between the mitral and aortic valves following mitral or aortic valve surgery, and uncontrolled adrenergic stimulation which may be observed with pheochromocytoma, and dobutamine stress echocardiogram.⁷ In contrast to dopamine and dobutamine,⁸ norepinephrine is not recognised as a potential precipitating factor for dynamic LVOTO.

Outcome and follow-up

Many weeks later, the patient developed sepsis with multi-organ failure. The family and medical team discontinued life-sustaining therapies 66 days after the aortic valve replacement.

Discussion

In a patient with a medical history of myocardial hypertrophy, the administration of norepinephrine to treat postoperative hypotension attributed to vasoplegia was associated with dynamic LVOTO, SAM and severe mitral valve regurgitation. Norepinephrine’s potential to precipitate dynamic LVOTO, while under-recognised, is consistent with its effect as a beta1 adrenergic receptor agonist. Beta-blockers are often used to prevent or improve left ventricular obstruction that occurs in certain cardiac conditions including hypertrophic cardiomyopathy. The sympathetic modulation by beta-blockers leads to the reduction in maximal contraction velocity and the deceleration of heart rate, which in turn leads to the change in the extent of SAM of the mitral valve and the magnitude of LVOTO. Therefore, worsening shock in predisposed patients receiving high doses of norepinephrine should prompt echocardiographic assessment for dynamic LVOTO.

Learning points.

• In predisposed patients, norepinephrine may be associated with left ventricular outflow tract obstruction (LVOTO).

• Phenylephrine or other pure vasoconstrictors, instead of norepinephrine, may be safer in patients who are predisposed to dynamic LVOTO.

• Worsening shock in predisposed patients receiving high doses of norepinephrine should prompt echocardiographic assessment for dynamic LVOTO.