Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome

Abstract

Background: Takotsubo syndrome is an acute cardiac emergency characterized by transient left ventricular systolic dysfunction typically following a stressful event. Despite its rapidly rising incidence, its pathophysiology remains poorly understood. Takotsubo syndrome may pass unrecognized, especially if timely diagnostic imaging is not performed. Defective myocardial calcium homeostasis is a central cause of contractile dysfunction and has not been explored in takotsubo syndrome. We aimed to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phases of takotsubo syndrome.

Methods: Twenty patients with takotsubo syndrome (63±12 years of age; 90% female) and 20 volunteers matched on age, sex, and cardiovascular risk factors (59±11 years of age; 70% female) were recruited from the Edinburgh Heart Centre between March 2020 and October 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during index hospitalization with repeat manganese-enhanced magnetic resonance imaging performed after at least 3 months.

Results: Compared with matched control volunteers, patients had a reduced left ventricular ejection fraction (51±11 versus 67±8%; P<0.001), increased left ventricular mass (86±11 versus 57±14 g/m2; P<0.001), and, in affected myocardial segments, elevated native T1 (1358±49 versus 1211±28 ms; P<0.001) and T2 (60±7 versus 38±3 ms; P<0.0001) values at their index presentation. During manganese-enhanced imaging, kinetic modeling demonstrated a substantial reduction in myocardial manganese uptake (5.1±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min], respectively; P<0.0001), consistent with markedly abnormal myocardial calcium handling. After recovery, left ejection fraction, left ventricular mass, and T2 values were comparable with those of matched control volunteers. Despite this, native and postmanganese T1 and myocardial manganese uptake remained abnormal compared with matched control volunteers (6.6±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min]; P<0.0001).

Conclusions: In patients with takotsubo syndrome, there is a profound perturbation of myocardial manganese uptake, which is most marked in the acute phase but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema, suggesting abnormal myocardial calcium handling may be implicated in the pathophysiology of takotsubo syndrome. Manganese-enhanced magnetic resonance imaging has major potential to assist in the diagnosis, characterization, and risk stratification of patients with takotsubo syndrome.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT04623788.

Keywords: calcium; magnetic resonance imaging; manganese; takotsubo cardiomyopathy.

Conflict of interest statement

CONFLICTS OF INTEREST DISCOLSURES

DEN and SIS hold unrestricted educational grants from Siemens Healthineers. GPM holds a research agreement with Circle CVi through University Hospitals of Leicester NHS Trust.

Figures

Figure 1. Consort Diagram

Figure 2. Anatomical Types of Takotsubo Syndrome

Short-axis and long-axis manganese-enhanced T1 maps and long-axis late-gadolinium images (10 min post contrast) in a matched control volunteer (panel A), and patients with apical (panel B), basal (panel C) and focal (panel D) takotsubo syndrome. Blue represents normal manganese uptake and green represents reduced manganese uptake and abnormal calcium handling.

Figure 3. Myocardial Edema and Left Ventricular Mass in Takotsubo Syndrome

Changes in left ventricular mass (panel A), native T2 (panel B), native T1 (panel C) and 30 min post manganese T1 maps (panel D). Correlations are seen between left ventricular mass and native T2 (E), left ventricular wall thickness and native T2 (F), myocardial manganese uptake and left ventricular mass (G) and myocardial manganese uptake and native T2 (H) during acute (red) and follow up (blue) scans.

Figure 4. Gadolinium Enhancement in Patients with Takotsubo Syndrome

Short-axis views of inferior late-gadolinium enhancement in a patient with spontaneous coronary artery dissection of the obtuse marginal branch of the left circumflex artery (A) and apical takotsubo (dual pathology). During acute imaging reduced myocardial manganese uptake (green) extends beyond the infarct region (B). Follow-up imaging demonstrates recovery of manganese uptake (blue) in regions affected by takotsubo syndrome with persistent abnormal manganese uptake (green) in the infarct region (C). Long-axis, four chamber view demonstrating characteristic hazy “incomplete nulling” in late-gadolinium enhancement imaging in a patient with apical takotsubo (D). Corresponding native T1 map during acute event demonstrates elevated native T1 in mid-ventricle and apical segments (E), with resolution on follow-up scans (F).

Figure 5. Manganese-enhanced Magnetic Resonance Imaging in Takotsubo Syndrome

Resolution of left ventricular systolic dysfunction (A) and apical ballooning (B and C) in a patient with takotsubo syndrome scanned 18 days after symptom onset. Long-axis (D) and short-axis (E) manganese-enhanced T1 map demonstrating typical apical pattern of takotsubo syndrome with abnormal myocardial manganese uptake (green) in mid-ventricular and apical segments with normal uptake (blue) in basal segments despite apparent restoration of normal cardiac function.

Figure 6. Myocardial Calcium Handling in Takotsubo Syndrome

Short-axis and long-axis manganese-enhanced T1 map in a (panel A) matched control volunteer and (panel B) patient with acute takotsubo syndrome demonstrating reduced manganese uptake (green). Short-axis and long-axis manganese-enhanced T1 maps at follow-up (panel C) demonstrating improvement (patchy) myocardial manganese uptake (as calculated by Patlak modelling) but persistent abnormalities compared to matched control volunteers (D).