Radosław Nowak

A signature of circulating microRNAs differentiates takotsubo cardiomyopathy from acute myocardial infarction

Aims Takotsubo cardiomyopathy (TTC) remains a potentially life-threatening disease, which is clinically indistinguishable from acute myocardial infarction (MI). Today, no established biomarkers are available for the early diagnosis of TTC and differentiation from MI. MicroRNAs (miRNAs/miRs) emerge as promising sensitive and specific biomarkers for cardiovascular disease. Thus, we sought to identify circulating miRNAs suitable for diagnosis of acute TTC and for distinguishing TTC from acute MI. Methods and results After miRNA profiling, eight miRNAs were selected for verification by real-time quantitative reverse transcription polymerase chain reaction in patients with TTC (n = 36), ST-segment elevation acute myocardial infarction (STEMI, n = 27), and healthy controls (n = 28). We quantitatively confirmed up-regulation of miR-16 and miR-26a in patients with TTC compared with healthy subjects (both, P < 0.001), and up-regulation of miR-16, miR-26a, and let-7f compared with STEMI patients (P < 0.0001, P < 0.05, and P < 0.05, respectively). Consistent with previous publications, cardiac specific miR-1 and miR-133a were up-regulated in STEMI patients compared with healthy controls (both, P < 0.0001). Moreover, miR-133a was substantially increased in patients with STEMI compared with TTC (P < 0.05). A unique signature comprising miR-1, miR-16, miR-26a, and miR-133a differentiated TTC from healthy subjects [area under the curve (AUC) 0.835, 95% CI 0.733–0.937, P < 0.0001] and from STEMI patients (AUC 0.881, 95% CI 0.793–0.968, P < 0.0001). This signature yielded a sensitivity of 74.19% and a specificity of 78.57% for TTC vs. healthy subjects, and a sensitivity of 96.77% and a specificity of 70.37% for TTC vs. STEMI patients. Additionally, we noticed a decrease of the endothelin-1 (ET-1)-regulating miRNA-125a-5p in parallel with a robust increase of ET-1 plasma levels in TTC compared with healthy subjects (P < 0.05). Conclusion The present study for the first time describes a signature of four circulating miRNAs as a robust biomarker to distinguish TTC from STEMI patients. The significant up-regulation of these stress- and depression-related miRNAs suggests a close connection of TTC with neuropsychiatric disorders. Moreover, decreased levels of miRNA125a-5p as well as increased plasma levels of its target ET-1 are in line with the microvascular spasm hypothesis of the TTC pathomechanism.

Ventricular rupture in Takotsubo cardiomyopathy

An 82-year-old female after a stress event, with no past medical history of cardiovascular diseases, was referred for emergency coronary angiography. She was suffering from chest pain, with a blood pressure of 124/67 mmHg and a heart rate of 76 b.p.m. Prominent ST-segment elevation in V1–V5 and increased troponin I level (14.82 ng/mL) suggested anteroseptal acute myocardial infarction. Urgent angiography documented …

Triple occurrence of Takotsubo cardiomyopathy

A 51 year-old woman after a quarrel with her husband and with no previous cardiovascular history was admitted to hospital with a suspicion of anterior myocardial infarction (MI) in 2005. She was suffering from chest pain; ECG documented ST-segment elevation in the V1–V3 leads and a positive troponin I level (2.8 ng/dL) was documented. An echocardiogram revealed akinesia of apical and mid-wall segments of left ventricular (LV) anterior wall and intraventricular septum with an ejection fraction (EF) of 45% (Fig. 1A, B). An urgent coronary angiography demonstrated no coronary artery disease (CAD). We observed full recovery with no LV contraction abnormalities at one-month follow-up. The subsequent focal type of Takotsubo cardiomyopathy (TTC) was diagnosed. Three years later, she presented with an inverse-type of TTC after knee surgery due to chest pain, ST-segment abnormalities in ECG and an increased troponin level (5.3 ng/dL). An echocardiogram and ventriculography revealed akinesia of all basal and mid-wall LV segments with an EF of 38% (Fig. 1C, D). We observed again a full clinical recovery with no LV wall motion abnormalities. A third hospitalisation, following a panic attack, occurred in 2009. The patient was referred for invasive diagnostics due to chest discomfort, ST-segment depression in ECG and a troponin I level of 1.1 ng/dL. Echocardiography and coronarography results were similar to those from the second episode (Fig. 1E, F). Therefore, a third occurrence of TTC was subsequently recognised. The most recent echocardiography showed normal LV contraction with an EF of 68% and normal longitudinal peak systolic strain for all LV regions (Fig. 1G, H). TTC, first described in 1990, usually affects postmenopausal women and is proceeded by psychological or physical stress. TTC mimics acute MI due to angina chest pain, ST-segment elevation pattern in ECG and a positive troponin level. However, obstructive CAD is in the majority of cases excluded. TTC, which is sometimes also known as apical ballooning syndrome, is predominantly characterised by transient, reversible, regional systolic dysfunction involving the LV apex and mid-ventricle with hyperkinesis of the basal LV segments. Case reports from the last 2 decades have also shown different faces of TTC concerning atypical TTCs such as inverse TTC with basal wall motion abnormalities, mid-segment TTC with akinesia presentation of all LV mid-segment and hyperkinesias of the basal and apical regions of LV, and focal TTC with regional wall motion disturbances. We here present a unique case of three TTC episodes in one patient after different stress events.

Left ventricular function after takotsubo is not fully recovered in long-term follow-up: A speckle tracking echocardiography study

BACKGROUND Complete improvement of left ventricle (LV) systolic function is an essential feature of takotsubo cardiomyopathy (TTC). It is suggested that 2-dimensional speckle tracking echocardiography (2D STE) can evaluate LV dysfunction more accurately than conventional echocardiography. Thus, the purpose of this research was to assertain whether LV function recovery is complete after the acute phase of TTC using 2D STE commencing 6 to 9 months after discharge. METHODS Thirty patients (29 females, 67 ± 11 years) with an apical ballooning TTC pattern 225.5 ± 27.4 days after their index event were enrolled. The control group consisted of 20 (19 females, 64 ± 9 years) age- and sex-matched volunteers without structural heart disease. Classic echocardiographic parameters, longitudinal strain and LV twist parameters were assessed and compared between the groups. RESULTS There were no differences in traditional LV systolic, diastolic parameters and in global peak longitudinal strain. In comparison to controls, patients with TTC had lower mean apical rotation (14.4° ± 6.5° vs. 18.3° ± 6.7°; p = 0.048), slower mean peak early diastolic apical rotation rate (-85.1-°/s ± 40.9-°/s vs -119.4-°/s ± 41.9-°/s; p = 0.006) and higher pre-stretch index in the apex (2.16, IQR 0.33-5.50 vs. 0.00, IQR 0.00-2.95, p = 0.008). CONCLUSIONS The improvement of LV function in patients with TTC as assessed by 2D STE may not always be complete. Some residual abnormalities in LV apex function were observed in long-term recovery following TTC episodes.

Clinical and laboratory assessment of patients with new-onset atrial fibrillation in acute myocardial infarction.

Background: new-onset atrial fibrillation (NOAF) is one of the complications of acute myocardial infarction (AMI), and is associated with poor outcome. The aim of the study was clinical and laboratory assessment of patients with NOAF in AMI. Material and methods: this is a retrospective, single-centre study of AMI patients with NOAF, who were admitted to Clinical Centre of Cardiology of the University Clinical Centre in Gdansk, from January 2016 to June 2018. The medical history, echocardiography parameters, AMI localization and infarcted-related artery as well as laboratory parameters at the admission and at the moment of NOAF onset were taken into further analyses. Results: from 1155 consecutive AMI patients 103 (8.9%) with NOAF were enrolled into the study. A significant increase in C-reactive protein (CRP) and high-sensitive Troponine I (hsTnI) level, whereas significant decrease in potassium and hemoglobin level was observed at the moment of NOAF in comparison to admission. Conclusions: our study suggests that markers of inflammation (CRP), myocardial necrosis (hsTnI), hemoglobin and serum potassium may be associated with NOAF in the setting on AMI. The aforementioned parameters are generally available and may be used as an inexpensive and rapid way to select patients who are at high risk of developing NOAF.

Emergency echocardiography to guide therapy in a patient with Takotsubo cardiomyopathy complicated with dynamic left ventricular outflow tract obstruction.

A 76-year-old woman with no previous cardiovascular history was admitted to an emergency setting with suspicion of ST-segment elevation acute myocardial infarction. She was suffering from retrosternal chest pain and dyspnoea just after a family quarrel. Clinical examination revealed a heart rate of 80 bpm, blood pressure of 110/50 mm Hg, and systolic murmur grade 4 in the Levine grading scale, with no signs of pulmonary congestion, peripheral oedema, or hepatomegaly. Electrocardiogram documented ST-segment elevation in precordial leads V2–V6 and lead I (Fig. 1A), and highly sensitive troponin T level was significantly elevated (1.3 ng/mL). Urgent coronary angiography was performed and demonstrated TIMI II grade flow in the left anterior descending artery, with no obstructive coronary artery disease or angiographic evidence of acute plaque rupture (Fig. 1B, C). An echocardiogram performed immediately after heart catheterisation revealed ellipsoidal asymmetric hypertrophy of the basal septum, apical ballooning, hyperkinesia of basal segments with left ventricular ejection fraction of 37%, and pronounced systolic anterior motion (SAM) (Fig. 1D, arrow) of both mitral leaflets causing mild mitral regurgitation (MR) and dynamic left ventricular outflow tract obstruction (LVOTO). The maximal velocity was 5.6 m/s and maximal peak gradient was 126 mm Hg (Fig. 1E). Based on the clinical and echocardiographic findings, therapy with bisoprolol 2.5 mg and intravenous fluid infusion was carefully initiated. Control echocardiography five days later showed hypokinesis of previously akinetic segments, normokinesis of basal segments, and no signs of SAM and dynamic LVOTO. The patient was discharged home with no cardiac symptoms, with the diagnosis of typical variant of Takotsubo cardiomyopathy (TTC). TTC is a reversible cardiomyopathy, usually affecting postmenopausal women with clinical presentation mimicking acute coronary syndrome. Since up to 10% of patients develop severe compl ications, despite the favourable long-term prognosis, TTC remains a life-threatening disease in the acute phase. We present a case of a woman with TTC complicated by acute SAM with mild MR and dynamic, severe LVOTO. Elderly women, with relatively small left ventricle cavity and septal bulge, are more likely to develop such complications. In patients with LVOTO continuous infusion of catecholamines or excessive diuretic therapy can increase the intraventricular pressure gradient that leads to further haemodynamic compromise and is thus not recommended. In such a clinical scenario careful intravenous fluid therapy, as well as use of intra-aortic balloon pump, should be considered. In patients without circulatory compromise with concomitant LVOTO, beta-blocker therapy is strongly recommended. However, the efficacy and safety of such treatment should be evaluated in further studies. This case highlights the role of immediate bedside echocardiography in a patient with TTC and systolic murmur, to guide immediate treatment strategy. Figure 1. A. ST-segment elevation in precordial leads V2– –V6 and lead I. B, C. Coronary angiography with no obstructive coronary artery disease. D, E. Asymmetric hypertrophy of the basal septum, apical ballooning, pronounced SAM (D, arrow) and dynamic LVOTO (E) A

Takotsubo cardiomyopathy induced by a suicide attempt

A 53-year-old male with no previous cardiovascular history was transferred from a psychiatric ward for urgent angiography with a diagnosis of acute coronary syndrome (ACS). The prior admission was due to a suicide attempt as a result of bipolar affective disease. The patient had been treated with paroxetine but had discontinued the therapy two months before the suicide attempt. As a result of jumping from the fourth floor, he experienced a fractured left forearm, fractured ribs, and pneumothorax. At the Coronary Care Unit (CCU), the patient denied stenocardia, but was admitted with ST-segment elevation in electrocardiogram and positive troponin I level of 0.471 ng/mL. Bedside echocardiography revealed akinesis of apical segments and hyperkinesis of basal segments with an estimated left ventricular (LV) ejection fraction (EF) of 40% (Fig. 1A, B). Moreover, mild mitral regurgitation and obstruction of LV outflow tract (maximal flow velocity of 4.3 m/s, maximal pressure gradient of 74 mm Hg, Fig. 1B, inset) were documented with a systolic anterior motion of mitral valve leaflets. In subsequent coronary angiography, no significant coronary artery disease was documented (Fig. 1C, D). Subsequent ventriculography confirmed a typical takotsubo cardiomyopathy (TTC). In echocardiography five days later, the LV function was essentially improved up to 55%. The acute course of TTC was uneventful, and on the fifth day of hospitalisation at the CCU the patient was transferred to the Department of Psychiatry for further treatment of his affective disorder. TTC is mainly precipitated by emotional stress, but the mechanism of reversible LVEF impairment remains unknown. Exaggerated sympathetic stimulation may play a key role in TTC above and beyond the burden of conventional cardiovascular risk factors. A suicide attempt comprises extreme emotional distress, and therefore could potentially provoke a TTC event. The susceptibility to TTC strongly related to psychiatric diseases such as chronic anxiety disorder or depression has been previously hypothesised. The abrupt interruption of selective serotonin reuptake inhibitor treatment has been postulated to increase the activation of the stress system and sympathetic nervous syndrome. The excessive activity of the noradrenergic system and hypothalamic-pituitary-adrenal-axis causes dysfunction of the serotoninergic system, increasing the risk of suicidal behaviour. We here present an interesting case of a suicide attempt triggering a TTC event. This particular case highlights the key role that mental disorders may play in TTC.

Giant cell arteritis involving the aorta and pulmonary trunk

Kobietę w wieku 67 lat przyjęto do Klinicznego Oddziału Ratunkowego z powodu narastającej od kilku godzin duszności i pierwszego w życiu epizodu silnego bólu w klatce piersiowej, zlokalizowanego zamostkowo oraz promieniującego do pleców. Dolegliwościom bólowym towarzyszyło uczucie osłabienia i mrowienia w obu kończynach dolnych. W wywiadzie chora podała nadciśnienie tętnicze występujące od 13 lat oraz palenie tytoniu od 20 lat. U pacjentki nie rozpoznawano wcześniej choroby wieńcowej. W badaniu EKG stwierdzono rytm zatokowy, patologiczny załamek Q w odprowadzeniu aVF i III; nie zaobserwowano cech ostrego niedokrwienia serca. W badaniach laboratoryjnych zanotowano nieznacznie podwyższone stężenie troponiny I — 0,43 ng/ml (N: < 0,03) i białka C-reaktywnego — 5,5 mg/l (N: < 5) oraz znacznie podwyższone stężenie D-dimerów — 25500 μg/l (N: < 500). Ze względu na całokształt obrazu klinicznego u pacjentki w pierwszej kolejności wykonano tomografię komputerową (TK) klatki piersiowej, w której uwidoczniono koncentrycznie pogrubiałą ścianę aorty piersiowej (do 12 mm) i pnia płucnego (do 10 mm) (ryc. 1). W badaniu USG, poza pogrubieniem ścian aorty, zaobserwowano znaczne, asymetryczne pogrubienie ścian tętnic szyjnych (do 3 mm) (ryc. 2). Nie stwierdzono odcinkowych zaburzeń kurczliwości w obrębie lewej komory. Wysunięto podejrzenie zapalenia dużych naczyń z zajęciem aorty i pnia płucnego. Włączono terapię steroidami. Stan pacjentki stopniowo się poprawiał. Na podstawie wyników badań u chorej ostatecznie rozpoznano olbrzymiokomórkowe zapalenie tętnic (GCA, giant cell arteritis) o nietypowym przebiegu. Po 3 miesiącach leczenia steroidami wykonano kontrolne badanie TK klatki piersiowej i jamy brzusznej, w którym wykazano całkowitą regresję zmian zapalnych w obrębie ściany pnia płucnego i tętnic odchodzących od łuku aorty oraz częściową w obrębie ściany aorty (ryc. 3). Powyżej przedstawiono bardzo rzadki przypadek równoczesnego zajęcia aorty i pnia płucnego w przebiegu GCA oraz związane z tym potencjalne problemy w diagnostyce różnicowej u pacjentki z silnym bólem w klatce piersiowej podwyższonym stężeniem troponiny i D-dimerów. We wstępnej diagnostyce różnicowej uwzględniono możliwość wystąpienia ostrego zespołu wieńcowego, ostrego zespołu aortalnego lub zatorowości płucnej — chorób o całkowicie odmiennym patomechaniźmie i leczeniu. Na podstawie TK wykluczono zatorowość płucną, ale ze względu na silne dolegliwości bólowe i stwierdzone pogrubienie ściany aorty nadal brano po uwagę obecność krwiaka śródściennego aorty. Zajęcie procesem chorobowym pnia płucnego i wszystkich tętnic odchodzących od łuku aorty w opisanym przypadku wykluczyło taką możliwość i pozwoliło na szybkie ustalenie właściwego rozpoznania.