Neurogenic Stunned Myocardium Progressing to Takotsubo Cardiomyopathy with Milrinone

Abstract

A 67-year-old female came with acute-onset headache and altered sensorium secondary to a ruptured right giant supraclinoid internal carotid artery aneurysm. Echocardiography revealed global wall motion abnormalities. She underwent aneurysm clipping on day 4 following ictus and her postoperative Glasgow Coma Scale (GCS) score was E₂V_TM₅. She developed an infarct in the caudate nucleus for which milrinone infusion was started. Following milrinone infusion her blood pressure dropped significantly. Despite stopping milrinone, it did not respond to noradrenaline or dopamine. Investigations revealed a troponin of 0.6 ng/mL, and electrocardiogram showed new ST-T changes in leads V₃-V₆. Echocardiography showed paradoxical apical excursion, suggestive of Takotsubo cardiomyopathy. She was started on vasopressin, her blood pressure stabilized, and noradrenaline was gradually tapered. Due to prolonged hypoperfusion, however, GCS dropped to E₂V_TM₃. Eventually, inotropes were stopped, and cardiac contractility recovered. The patient had a sudden drop in GCS on postoperative day 25 and died.

Keywords

neurogenic stunned myocardium - Takotsubo cardiomyopathy - milrinone

Introduction

Neurogenic stunned myocardium (NSM) and Takotsubo cardiomyopathy (TTC) are known complications following aneurysmal subarachnoid hemorrhage (aSAH).[1] TTC is characterized by mainly apical and septal dysfunction with the base of the heart less affected. The electrocardiogram (ECG) picture of TTC can mimic myocardial infarction (MI); however, coronary angiogram is usually normal.[2] [3] Here, we describe a rare instance of NSM progressing to TTC in a patient, precipitated by milrinone, which was managed with vasopressin infusion. Consent was obtained for publication from the patient's relatives.

Case Report

A 67-year-old female was brought to the casualty with 1 day history of acute headache associated with altered sensorium. Per her relatives, she had no comorbid conditions. Her Glasgow Coma Scale (GCS) score at presentation was E₂V₁M₅, necessitating tracheal intubation for airway protection. Laboratory investigations were normal except for mild anemia (hemoglobin 10.7 g/dL). A noncontrast computed tomography (CT) scan revealed a modified Fisher (MFS) grade IV subarachnoid hemorrhage (SAH). ECG showed inverted T-waves in leads V₃-V₆ with normal ST segment. Considering the patient's age and lack of previous cardiovascular history, an echocardiography was performed which revealed mild wall motion abnormalities in distal intraventricular septum (IVS), apex, and anterolateral wall with mild left ventricular (LV) dysfunction. Ejection fraction (EF) was 44% with grade 1 diastolic dysfunction. Troponin-T was 0.8 ng/mL and a repeat done 12 hours later was 0.71 ng/mL. CT angiography and digital subtraction angiography revealed a giant saccular aneurysm arising from the ophthalmic segment of the right internal carotid artery ([Fig. 1]). Considering the history of aSAH and mildly elevated troponin, a diagnosis of NSM was made. The patient underwent craniotomy and clipping of the aneurysm along with evacuation of SAH and cisternostomy on day 4 following ictus. In the operating room, in addition to routine monitoring, continuous arterial blood pressure (BP) and central venous pressure were also monitored throughout the procedure. Intraoperatively, there was rupture of aneurysm, which was controlled with temporary clips, before securing the aneurysm. Intraoperative blood loss was 2,500 mL, which was replaced with 1,100 mL packed red cells and 800 mL of fresh frozen plasma. Noradrenaline infusion was started to augment BP and mean arterial pressure (MAP) was maintained above 70 mm Hg; no hypotensive episodes occurred during the procedure. The patient was shifted to the neurosurgical intensive care unit (ICU) for elective postoperative ventilation with noradrenaline infusion at 0.2 mcg/kg/min to maintain a systolic BP between 140 and 160 mm Hg. In the ICU, the noradrenaline was slowly tapered to 0.05 mcg/kg/min, maintaining the same BP, and the patient's postoperative GCS was E₂V_TM₅.

Fig. 1 Digital subtraction angiography (DSA) depicting dorsal ophthalmic segment giant internal carotid artery (ICA) aneurysm.

On postoperative day (POD) 1, a CT scan revealed a new patchy right middle cerebral artery territory infarct and hydrocephalus. Due to her high risk of vasospasm, as part of our institutional protocol for MFS III and IV aSAH, milrinone infusion at 0.2 mcg/kg/min without a bolus dose was added, after first increasing noradrenaline to 0.1 mcg/kg/min, to treat any possible vasospasm after considering the risk–benefit.[4] Within 5 to 10 minutes of starting the milrinone infusion, her BP fell precipitously from 160/90 mmHg to 100/50 mm Hg and heart rate increased from 80 to 130 beats/min. New ECG changes were also noted on the monitor. Over the next hour, noradrenaline infusion was increased from 0.1 to 0.4mcg/kg/min, but the BP continued to fall with arterial BP showing 60/40 mm Hg. A 12-lead ECG revealed new-onset ST depressions in leads V₃-V₆. Suspecting MI, milrinone was stopped and dopamine started at 10 mcg/kg/min. Fifteen minutes after initiating the dopamine infusion, however, bedside echocardiography showed ballooning of the apex but normal contractility at the base. Dopamine was immediately stopped, and vasopressin infusion was started at 0.1 U/min. A two-dimensional echocardiography revealed new wall motion abnormalities in the apical regions of IVS with severe LV dysfunction and EF of 33%. Troponin-T sent following the ECG changes was 0.6 ng/mL, showing a decreasing trend, reducing the likelihood of MI. BP gradually improved to 80/50 mm Hg despite tapering noradrenaline to 0.15 mcg/kg/min while maintaining the vasopressin infusion. After the BP reached 140/100 mm Hg, vasopressin was gradually tapered and stopped and noradrenaline infusion was kept at 0.15 mcg/kg/min, targeting a MAP above 100 mm Hg.

The patient, however, deteriorated with GCS of E₂V_TM₃ with both pupils reactive to light. Following tracheostomy, she was weaned off the ventilator. Echocardiography done 4 days later showed improvement in contractility of IVS and apex with mild to moderate LV dysfunction. Troponin-T levels remained below 2 ng/mL. She was shifted to the ward on POD 8 with static neurological status. However, on POD 25, she developed a sudden drop in GCS. On examination, she had bilateral dilated and nonreactive pupils. She was shifted back into the ICU for resuscitation, but she died the same day.

Discussion

Cardiac complications are common after aSAH with the spectrum ranging from sinus bradycardia and nonsignificant ST-T changes on the ECG to gross wall motion abnormalities secondary to NSM, MI, or TTC.[1]

NSM and TTC are stress-induced cardiac wall motion abnormalities. While NSM has global hypokinesia, TTC has predominantly apical involvement. The underlying cause for both being catecholamine surge following acute stress.[2] [3] [5] Milrinone, a phosphodiesterase-3 inhibitor, acts as an inotrope on the heart and is a vasodilator that is used to relieve vasospasm following aSAH.[6] Milrinone does not stimulate catecholamine receptors and has also been used to improve contractility in TTC, which worsens with catecholamines.[3] [7] However, experiments by Ali et al demonstrated TTC-like cardiac dysfunction precipitated solely by milrinone in rats.[8] But we were unable to find reports of the same in human beings. Levosimendan has also been used to improve contractility in TTC.[9] Our hospital, however, does not stock levosimendan, and hence we used vasopressin instead to augment BP.[10] However, data are lacking on the role of vasopressin in patients with TTC.

The sequence of events leads us to suspect milrinone as the possible cause for the progression of NSM to TTC in this patient. Given the role milrinone plays in patients with aSAH, we feel that clinicians who manage these patients should be made aware of this possibility, when patients who have NSM develop new ECG changes, hypotension, and wall motion abnormalities with milrinone infusion.

Conflict of Interest

None declared.

• References

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Publication History

Article published online:
12 May 2025