Caroline Scally

Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy

Background: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined. Methods: In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy. Results: Participants were predominantly middle-age (64±11 years) women (97%). Although takotsubo cardiomyopathy occurred 20 (range 13–39) months before the study, the majority (88%) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0–76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/VCO2 slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, −16±1.0 versus −23±1.5%, P<0.001; global longitudinal strain, −17±1 versus −20±1%, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms, P<0.001), and impaired cardiac energetic status (phosphocreatine/&ggr;-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001). Conclusions: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.

Right Ventricular Involvement and Recovery After Acute Stress-Induced (Tako-tsubo) Cardiomyopathy.

Acute stress-induced (Tako-tsubo) cardiomyopathy is an increasingly recognized but insufficiently characterized syndrome. Here, we investigate the pathophysiology of right ventricular (RV) involvement in Tako-tsubo and its recovery time course. We prospectively recruited 31 patients with Tako-tsubo with predominantly ST-elevation electrocardiogram and 18 controls of similar gender, age, and co-morbidity distribution. Patients underwent echocardiography and cardiac magnetic resonance (CMR) imaging on a 3T Philips scanner in the acute phase (day 0 to 3 after presentation) and at 4-months follow-up. Visually, echocardiography was able to identify only 52% of patients who showed RV wall motion abnormalities on CMR. Only CMR-derived RV ejection fraction (p = 0.01) and echocardiography-estimated pulmonary artery pressure (p = 0.01) identify RV functional involvement in the acute phase. Although RV ejection fraction normalizes in most patients by 4 months, acutely there is RV myocardial edema in both functioning and malfunctioning segments, as measured by prolonged native T1 mapping (p = 0.02 for both vs controls), and this persists at 4 months in the acutely malfunctioning segments (p = 0.002 vs controls). The extracellular volume fraction was significantly increased acutely in all RV segments and remained increased at follow-up compared with controls (p = 0.004 for all). In conclusion, in a Tako-tsubo population presenting predominantly with ST-elevation electrocardiogram, we demonstrate that although RV functional involvement is seen in only half of the patients, RV myocardial edema is present acutely throughout the RV myocardium in all patients and results in microscopic fibrosis at 4-month follow-up.

Voltage-gated potassium channel antibody-related encephalopathy: a case which may extend the documented phenotype of this condition

A 51-year-old man presented with a focal epileptic, fluctuating encephalopathy. Antibodies to voltage-gated potassium channels (VGKC-Abs) were detected in his serum. Several features of this case were different from those previously reported in VGKC-Ab-associated encephalitis, illustrating that it may have a broader phenotype than previously documented. These features were: excess hepatic iron deposits without cirrhosis, reduced consciousness and fluctuating neurological signs. Previous history included personality change, depression, type 2 diabetes mellitus, pupil sparing third nerve palsy and epilepsy secondary to a head injury. He had never drunk alcohol and had recovered from a similar episode 4 years previously. Both episodes resolved after approximately 2 months. The cerebrospinal fluid had a raised protein content but no organisms. The patient was heterozygous for C282Y and negative for H63D mutations excluding classical idiopathic haemochromatosis. He recovered with supportive care to his premorbid level of health.

Takotsubo cardiomyopathy with severe bradyarrhythmia following epidural insertion

We present a case of takotsubo cardiomyopathy (TTC) with ventricular stand still and atrioventricular block. TTC can mimic ST elevation myocardial infarction and heart failure, but in this case resulted in a severe cardiac conduction disorder and ventricular standstill. This is a recognised but unusual presentation and serves as a lesson to those undertaking anaesthetics to be vigilant for TTC.

Author's Reply: Persistence of Deformation Abnormalities and Detection of Fibrosis at 4-Month Follow-up in Patients with Takotsubo Syndrome

magnetic resonance imaging and echocardiography at 1-year followup, or at any time between 4months and 1 year (as the authors allude to), to evaluate their course of recovery and the possible presence or absence of restoration to normalcy. Third, a ‘‘chronic TTS condition’’ (i.e., persisting symptoms both at rest andwith exercise) has been suspected, and the authors provide us with the diagnostic blueprint for the objective evaluation of such patients with TTS at follow-up. Fourth, was there any correlation between the acute and 4-month echocardiographic or cardiac magnetic resonance imaging metrics and the peak levels of troponin I, C-reactive protein, and brain natriuretic peptide? Fifth, the intriguing finding of persistently increased extracellular matrix volume at 4-month follow-up on cardiac magnetic resonance imaging testing, attributed tomicroscopic fibrosis, by the timemyocardial edema has probably subsided, and affecting the heart globally (i.e., both the acutely abnormally and normally or supernormally contracting myocardial regions), may have pathophysiologic connotations. Probably there are acute cardiomyocyte injurious influences (no matter the mechanism of TTS) also affecting normally and supernormally (i.e., base of the heart) functioning cardiac territories.

Dynamic changes of the extracellular matrix after acute tako-tsubo cardiomyopathy

Methods Eleven patients (10F, mean age 56±16yrs) with a clear diagnosis of ST-elevation TTC and emotional trigger were prospectively enrolled and underwent cardiac magnetic resonance acutely (day 0-3) and after 4 months on a Philips 3T Achieva scanner. Native 3-3-5 (MOLLI) T1 mapping was applied acutely, and both native and postcontrast T1 mapping were performed at 4 months followup. Eleven healthy controls underwent only native T1 mapping. T1 maps were: generated using in-house software written in IDL (Exelis. Boulder CO, USA); quality controlled with chi-square maps; and imported into Segment (Medviso, Lund University, Sweden), where T1 values were generated for 16 segments. Extracellular volumes (ECV) were calculated for the follow-up scan using: ECV=(1-hermatocrit)(ΔR1myocardium/ ΔR1blood) Segments were grouped according to their wall motion (WM) on the acute scan (normal/abnormal).

Right ventricular involvement in Tako-tsubo cardiomyopathy - insights from cardiovascular magnetic resonance

Methods 21 patients, mean age 66 (range 41-87 years) with a clear diagnosis of TTC (14 with ST-elevation, 16 with apical ballooning ) and emotional trigger were prospectively studied. CMR-derived LV and RV volumes and EF, RV shapes, RV wall motion index (WMSI, 6-segment model) and Echocardiography derived Pulmonary artery pressure (Pap), tricuspid annular E’,A’,S’, pansystolic excursion (TAPSE) were measured acutely (day 0-3) and after 4 months follow-up.