Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience.

BACKGROUND: Takotsubo syndrome is an increasingly recognized cause of chest pain and occasionally of cardiogenic shock. Despite rapid improvement of the left ventricular (LV) ejection fraction, recent registry data raise concerns about long-term prognosis. The aim of this study was to test the hypothesis that restoration of normal ejection fraction after acute takotsubo syndrome is not equivalent to full functional recovery. METHODS: Fifty-two patients with takotsubo syndrome (according to the Mayo Clinic criteria plus cardiac magnetic resonance imaging to exclude myocardial infarction) and 44 healthy control subjects of the same age, gender, and cardiovascular comorbidity distribution were prospectively recruited. The focus of the investigation was on patients with takotsubo syndrome presenting with ST-segment elevation-type electrocardiographic findings or malignant arrhythmias and with LV apical ballooning variant, and a 4-month recovery endpoint was assessed. Patients underwent echocardiographic assessment of LV myocardial deformation (global longitudinal, radial, and circumferential strain; LV twist, torsion, and untwist; and time to peak twist and untwist) and assessment of LV myocardial structure by pre- and post-contrast-enhanced cardiac magnetic resonance by T1 mapping acutely and at 4-month follow-up. Control subjects underwent a single-time-point investigation. Data were analyzed using paired or unpaired tests, as appropriate for their distribution, and corrected for multiple comparisons. RESULTS: The patients' mean age was 66 years (range, 28-87 years), and 92% were women. All abnormal echocardiographic indices observed acutely in patients with takotsubo syndrome improved (but did not necessarily normalize) at follow-up. Significant mechanotemporal alterations characterizing both systole (global longitudinal strain and apical circumferential strain, P < .01 for both; LV twist, twist rate, and torsion, P < .0001 for all) and diastole (untwist rate and time to peak untwisting, P < .001 for both) persisted at 4-month follow-up compared with control subjects, despite normalization of LV ejection fraction and volumes. Although native T1 (which demonstrates edema) normalized at 4-months follow-up only in segments contracting normally during the acute phase (T1 = 1,180 ± 40.6 msec [normally contracting segments, P = .20 vs control value of 1,189 ± 16 msec] and T1 = 1,208 ± 60.3 msec [dysfunctional segments, P < .05 vs control]), the extracellular volume fraction (which demonstrates diffuse fibrosis) remained significantly abnormal in all LV segments (whether normally contracting [0.328 ± 0.043, P < .001] or ballooning during acute presentation [0.320 ± 0.044, P < .001], both vs control value of 0.273 ± 0.045). CONCLUSIONS: In patients with the most clinically severe spectrum of takotsubo cardiomyopathy, regional LV systolic and diastolic deformation abnormalities persist beyond the acute event, despite normalization of global LV ejection fraction and size. In addition, although myocardial edema partly subsides, a process of global microscopic fibrosis develops in its place, detected as early as 4 months.

3D MRI analysis of the lower legs of treated idiopathic congenital talipes equinovarus (clubfoot).

BACKGROUND: Idiopathic congenital talipes equinovarus (CTEV) is the commonest form of clubfoot. Its exact cause is unknown, although it is related to limb development. The aim of this study was to quantify the anatomy of the muscle, subcutaneous fat, tibia, fibula and arteries in the lower legs of teenagers and young adults with CTEV using 3D magnetic resonance imaging (MRI), and thus to investigate the anatomical differences between CTEV participants and controls. METHODOLOGY/PRINCIPAL FINDINGS: The lower legs of six CTEV (2 bilateral, 4 unilateral) and five control young adults (age 12-28) were imaged using a 3T MRI Philips scanner. 5 of the CTEV participants had undergone soft-tissue and capsular release surgery. 3D T1-weighted and 3D magnetic resonance angiography (MRA) images were acquired. Segmentation software was used for volumetric, anatomical and image analysis. Kolmogorov-Smirnov tests were performed. The volumes of the lower affected leg, muscle, tibia and fibula in unilateral CTEV participants were consistently smaller compared to their contralateral unaffected leg, this was most pronounced in muscle. The proportion of muscle in affected CTEV legs was significantly reduced compared with control and unaffected CTEV legs, whilst proportion of muscular fat increased. No spatial abnormalities in the location or branching of arteries were detected, but hypoplastic anomalies were observed. CONCLUSIONS/SIGNIFICANCE: Combining 3D MRI and MRA is effective for quantitatively characterizing CTEV anatomy. Reduction in leg muscle volume appears to be a sensitive marker. Since 5/6 CTEV cases had soft-tissue surgery, further work is required to confirm that the treatment did not affect the MRI features observed. We propose that the proportion of muscle and intra-muscular fat within the lower leg could provide a valuable addition to current clinical CTEV classification. These measures could be useful for clinical care and guiding treatment pathways, as well as treatment research and clinical audit.