Aims The risk of life-threatening ventricular arrhythmias (LTVA) has been reported to be lower in Takotsubo syndrome (TS) compared with ST-elevation myocardial infarction (STEMI). However, the extent to which these differences relate to the fact that most patients with TS are women (who have a lower risk of LTVA) and a relatively larger proportion of patients with STEMI are men is incompletely understood. We aimed to investigate the risk of LTVA or death in sex-matched and age-matched patients with TS, anterior STEMI, and non-anterior STEMI. Methods and results We systematically reviewed the charts of all patients with TS who were treated at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2008 and 2019. A total of 155 patients with confirmed TS (according to the European Society of Cardiology diagnostic criteria for TS) were sex-matched and age-matched 1:1:1 to patients with anterior and non-anterior STEMI. Baseline characteristics and in-hospital outcomes were recorded directly from the patient charts for all patients, and all admission electrocardiographs were analysed. The primary outcome was the composite of death or LTVA [defined as sustained ventricular tachycardia (>30 s) or ventricular fibrillation] within 72 h. The risk of LTVA or death within 72 h after admission was considerably lower in TS (2.6%) vs. anterior STEMI (14%; P = 0.002) and non-anterior STEMI (9.0%; P = 0.02), despite similar or greater risks of acute heart failure, and similar risks of cardiogenic shock. Compared with STEMI, TS was associated with a lower risk of sustained and non-sustained ventricular tachycardia and ventricular fibrillation. Conclusions In a predominantly female age-matched and sex-matched cohort of patients with TS, anterior STEMI, and non-anterior STEMI, the adjusted risk of in-hospital LTVA or death was considerably lower in TS compared with STEMI, despite similar or greater risk of acute heart failure and similar risk of cardiogenic shock.
Aims Takotsubo syndrome (TTS) is an acute potentially reversible cardiac syndrome characterized by variable regional myocardial akinesia that cannot be attributed to a culprit coronary artery occlusion. TTS is an important differential diagnosis of acute heart failure where brain natriuretic peptides are elevated. Sacubitril/valsartan is a novel and effective pharmacological agent for the treatment of patients with heart failure. Our aim was to explore whether treatment with sacubitril/valsartan could prevent isoprenaline-induced takotsubo-like phenotype in rats. Methods and results A total number of 186 Sprague-Dawley male rats were randomized to receive pretreatment with water (CONTROL, n = 62), valsartan (VAL, n = 62), or sacubitril/valsartan (SAC/VAL, n = 62) before receiving isoprenaline for induction of TTS. We recorded heart rate and blood pressure invasively. Cardiac morphology and function were evaluated by high-resolution echocardiography 90 min after the administration of isoprenaline. We documented the survival rate at the time of echocardiography. Compared with the CONTROL group, the SAC/VAL group had less pronounced TTS-like cardiac dysfunction and lower mortality rate, while the VAL group did not differ. Heart rate and blood pressure were not significantly different between the groups. Analysis of cardiac lipids was performed with mass spectrometry. The VAL and SAC/VAL groups had significantly higher levels of lysophosphatidylcholine (LPC), in particular LPC 18:1 and LPC 16:0. Conclusions Pretreatment with sacubitril/valsartan but not with valsartan reduces mortality and attenuates isoprenalineinduced apical akinesia in the TTS-like model in rats. Sacubitril/valsartan could be a potential treatment option in patients with TTS in humans.
Background Cardiac troponin T (cTnT) and troponin I (cTnI) are expressed as an obligate 1:1 complex in the myocardium. However, blood levels of cTnI often rise much higher than cTnT in myocardial infarction (MI), whereas cTnT is often higher in patients with stable conditions such as atrial fibrillation. Here we examine hs-cTnI and hs-cTnT after different durations of experimental cardiac ischemia. Methods hs-cTnI, hs-cTnT, and the hs-cTnT/hs-cTnI ratio were measured in plasma samples from rats before and at 30 and 120 minutes after 5, 10, 15, and 30 minutes of myocardial ischemia. The animals were killed after 120 minutes of reperfusion, and the infarct volume and volume at risk were measured. hs-cTnI, hs-cTnT, and the hs-cTnT/hs-cTnI ratio were also measured in plasma samples collected from patients with ST-elevation myocardial infarction. Results hs-cTnT and hs-cTnI increased over ten-fold in all rats subjected to ischemia. The increase of hs-cTnI and hs-cTnT after 30 minutes was similar, resulting in a hs-cTnI/hs-cTnT ratio around 1. The hs-cTnI/hs-cTnT ratio was also around 1 in blood samples collected at 120 minutes in rats subjected to 5 or 10 minutes of ischemia where no localized necrosis was observed. In contrast, the hs-cTnI/hs-cTnT ratio at 2 hours was 3.6-5.5 after longer ischemia that induced cardiac necrosis. The large hs-cTnI/hs-cTnT ratio was confirmed in patients with anterior STEMI. Conclusion Both hs-cTnI and hs-cTnT increased similarly after brief periods of ischemia that did not cause overt necrosis, whereas the hs-cTnI/hs-cTnT ratio tended to increase following longer ischemia that induced substantial necrosis. A low hs-cTnI/hs-cTnT ratio around 1 may signify non-necrotic cTn release.
Introduction and Objectives Using existing transthoracic echocardiographic indices to quantify left ventricular wall motion abnormalities (WMAs) can be difficult due to the variations in the location of the abnormalities within the left ventricle, the quality of examinations, and the inter‐/intra‐observer variability of available indices. This study aimed to evaluate a new approach for measuring the extent of WMA by calculating the percentage of abnormal wall motion and comparing it to the wall motion score index (WMSI). The study also sought to assess inter‐ and intra‐observer variability. Methods The study included 140 echocardiograms from 54 patients presenting with ST‐elevation myocardial infarction or Takotsubo syndrome. All patients underwent an echocardiographic examination according to a standard protocol and the images were used to measure the extent of akinesia (proportion akinesia, PrA), akinesia and hypokinesia (proportion akinesia/hypokinesia, PrAH), and WMSI. The inter‐observer variability between the two operators was analyzed. The intra‐observer analysis was performed by one observer using the same images at least 1 month after the first measurement. The agreement was analyzed using the Pearson correlation coefficient and Bland‐Altman plots. Results Inter‐ and intra‐observer variability for PrA and PrAH were low and comparable to those for WMSI. Conclusion PrA and PrAH are reliable and reproducible echocardiographic methods for the evaluation of left ventricular wall motion.
Background Takotsubo syndrome (TS) and ST-elevation myocardial infarction (STEMI) are both characterized by sudden cessation of myocardial contractions (myocardial stunning) as well as elevation of cardiac troponins and B-type natriuretic peptides (BNP). Whereas STEMI results in variable degrees of necrosis and persistent cardiac dysfunction, TS results in little to any necrosis and full recovery of cardiac function. No “head-to-head” comparison of the temporal resolution of myocardial stunning and serum biomarkers in STEMI versus takotsubo has been done. Purpose To compare the time course of the recovery of cardiac function and serum biomarkers over the acute and subacute phases of takotsubo and STEMI, with patients with STEMI further subdivided into anterior and non-anterior STEMI. Method The Stunning In Takotsubo and Acute Myocardial Infarction (STAMI) study is a prospective, multi-center study that enrolls patients with TS or STEMI without known pre-existing cardiac dysfunction. Echocardiography, laboratory testing (including troponins and NT-proBNP), and ECG are acquired within 4 hours after acute coronary angiography and at 24±6, 48±12, 72±12 hours and 7±1, 14±2, and 30±2 days. The primary endpoint is the proportion of reversible myocardial akinesia resolved after 72 hours (Figure 1), as determined by echocardiography. Secondary endpoints include troponin-I, troponin-T, and NT-proBNP. Results Preliminary results from 155 patients with STEMI (78 anterior STEMI and 77 non-anterior STEMI) and 32 patients with TS are presented in Figure 1. Mean (SD) age was similar for patients with takotsubo (67±14), anterior STEMI (68±11), and non-anterior STEMI (68±10). All 3 groups showed substantial recovery of cardiac function over the course of the study, with the most pronounced recovery of cardiac function in TS. Compared to both STEMI groups, the TS group also had lower troponin-I to troponin-T ratio, and higher NT-proBNP (Figure 2). The proportion of reversible akinesia that had recovered at 72 hours was similar in patients with TS, anterior STEMI and non-anterior STEMI (p=0.8414). Conclusion The STAMI study will provide the comprehensive assessment of cardiac function and serum biomarker profile of patients with takotsubo and STEMI over the early course of the disease. Preliminary data from the study suggest that early myocardial functional recovery is more substantial but follows a similar time-course in takotsubo and STEMI. The differences in the magnitude of troponin elevation after takotsubo versus STEMI were more pronounced for troponin-I than T. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ERC - European Research Council
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