Novel Imaging and Genetic Risk Markers in Takotsubo Syndrome.
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ABSTRACT:
SUBMITTER: Arcari L
PROVIDER: S-EPMC8415918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9-14.8, HR = 7.8 95% CI 2.4-25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6-52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.
| S-EPMC8368165 | biostudies-literature
Project description:Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, with a hospital-mortality rate similar to acute coronary syndrome (ACS). However, the aetiology of TTS is still unknown. In the present study, a multivariate pattern analysis using machine learning with multimodal magnetic resonance imaging (MRI) data of the human brain of TTS patients and age- and gender-matched healthy control subjects was performed. We found consistent structural and functional alterations in TTS patients compared to the control group. In particular, anatomical and neurophysiological measures from brain regions constituting the emotional-autonomic control system contributed to a prediction accuracy of more than 82%. Thus, our findings demonstrate homogeneous neuronal alterations in TTS patients and substantiate the importance of the concept of a brain-heart interaction in TTS.
| S-EPMC5511237 | biostudies-literature
Project description:BackgroundTakotsubo 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.MethodsTwenty patients with takotsubo syndrome (64±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.ResultsCompared 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).ConclusionsIn 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.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT04623788.
| S-EPMC7613919 | biostudies-literature
Project description:Takotsubo syndrome (TTS), recognized as stress's cardiomyopathy, or as left ventricular apical balloon syndrome in recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the limited understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in recent years, and particularly correlated to the SARS-CoV-2 pandemic, leads us to the imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and of targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial forms of TTS have been described. However, a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we here conducted a systematic review of the literature before June 2021, to contribute to the identification of potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but few in number and with diverse limitations. Consequently, we concluded that further work is needed to address the gaps discussed, and clear evidence may arrive by using multi-omics investigations.
| S-EPMC8471495 | biostudies-literature
Project description:Background: Takotsubo cardiomyopathy is triggered by emotional or physical stress. It is defined as a reversible myocardial dysfunction, usually with apical ballooning aspect due to apical akinesia associated with hyperkinetic basal left ventricular contraction. Described in cases of viral infections such as influenza, only few have been reported associated with novel coronavirus disease 2019 (COVID-19) in the recent pandemic. Case summary: A 79-years-old man, with cardiovascular risk factors (type 2 diabetes and hypertension) and chronic kidney disease, presented to the emergency room for severe dyspnea after 8 days of presenting respiratory symptoms and fever. Baseline electrocardiogram (ECG) was normal, but he presented marked inflammatory syndrome. He was transferred to an intensive care unit to receive mechanical ventilation within 6 h, due to acute respiratory distress syndrome. He presented circulatory failure 2 days after, requiring norepinephrine support (up to up to 1.04 μg/kg/min). Troponin T was elevated (637 ng/l). ECG showed diffuse T wave inversion. Echocardiography showed reduced left ventricular ejection fraction (LVEF 40%), with visual signs of Takotsubo cardiomyopathy. Cardiac failure resolved after 24 h with troponin T decrease (433 ng/l) and restoration of cardiac function (LVEF 60% with regression of Takotsubo features). Patient died after 15 days of ICU admission, due to septic shock from ventilator-acquired pneumonia. Cardiac function was then normal. Conclusion: Mechanisms of Takotsubo cardiomyopathy in viral infections include catecholamine-induced myocardial toxicity and inflammation related to sepsis. Differential diagnoses include myocarditis and myocardial infarction. Evidence of the benefit of immunomodulatory drugs and dexamethasone are growing to support this hypothesis in COVID-19.
| S-EPMC7937625 | biostudies-literature
Project description:A healthy 66-year-old female presented to the emergency department with acute chest pain, T-wave inversion in the anterior leads, and elevated troponin-I. Coronary angiography showed a stenosis in the midportion of the left anterior descending coronary artery (LAD), which did not wrap the left ventricle (LV) apex. LV angiography demonstrated a large LV apical akinetic systolic ballooning with a 45% ejection fraction. Fractional flow reserve (FFR) of LAD lesion was 0.71. Percutaneous intervention was performed. At six months, transthoracic echocardiography was normal. Fifteen months later, the patient presented with chest pain and a small rise in troponin-I. Coronary angiogram was unchanged. Repeat FFR in distal LAD was 0.86 and left ventriculography was normal. Diagnostic criteria for Takotsubo cardiomyopathy (TTC) require the absence of obstructive coronary artery disease. In the present case, TTC was highly suspected on the basis of typical LV apex ballooning. However, significant ischemia in the same territory was demonstrated by positive FFR, which could not be falsely positive in this context. Current TTC diagnostic criteria increase specificity for diagnosing TTC. This case reminds us that it is at the price of reduced sensitivity, since there is no reason to believe that coronary lesions may protect from TTC.
| S-EPMC7060413 | biostudies-literature
Project description:AimsAtrial fibrillation (AF) is associated with adverse outcome. Whether recently discovered genetic risk markers improve AF risk prediction is unknown.Methods and resultsWe derived and validated a novel AF risk prediction model from 32 possible predictors in the Women's Health Study (WHS), a cohort of 20 822 women without cardiovascular disease (CVD) at baseline followed prospectively for incident AF (median: 14.5 years). We then created a genetic risk score (GRS) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS. The newly derived WHS AF risk algorithm included terms for age, weight, height, systolic blood pressure, alcohol use, and smoking (current and past). In the validation cohort, this model was well calibrated with good discrimination [C-index (95% CI) = 0.718 (0.684-0.753)] and improved all reclassification indices when compared with age alone. The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [0.741 (0.709-0.774); P = 0.001], the category-less net reclassification [0.490 (0.301-0.670); P < 0.0001], and the integrated discrimination improvement [0.00526 (0.0033-0.0076); P < 0.0001]. However, there was no improvement in net reclassification into 10-year risk categories of <1, 1-5, and 5+% [0.041 (-0.044-0.12); P = 0.33].ConclusionAmong women without CVD, a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF. The addition of genetic information resulted in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories.
| S-EPMC3730133 | biostudies-literature
Project description:While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415-0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.
| S-EPMC4976361 | biostudies-literature
Project description:AimsTakotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction with symptoms and electrocardiographic changes mimicking acute myocardial infarction (AMI). The objective of this study was to evaluate in-hospital death and hospital readmission in patients with TTS and to compare outcomes to patients with AMI.Methods and resultsPatients diagnosed with TTS and AMI were identified using the United States Nationwide Readmission Database from 2010 to 2014. In-hospital outcomes for the index admission, and rates and causes of 30 day readmissions were compared between TTS patients and AMI patients without TTS. Sixty-one thousand, four hundred, and twelve patients with TTS and 3 470 011 patients with AMI without TTS were identified. Patients with TTS were younger, more often women (89% vs. 41%), and less likely to have cardiovascular risk factors than AMI patients. Mortality during the index admission was lower in TTS compared with AMI (2.3% vs. 10.2%, P < 0.0001). Cardiogenic shock occurred at the same frequency (5.7%) with TTS or AMI. Among TTS survivors, 7132 patients (11.9%) were readmitted within 30 days, and mortality associated with readmission was 3.5%. The most common reason for readmission after TTS was heart failure (HF; 10.6% of readmissions).ConclusionTakotsubo syndrome is associated with substantial morbidity and mortality. Although outcomes are more favourable than AMI, approximately 2% of patients died in hospital and approximately 12% of survivors were readmitted within 30 days; HF was the most frequent indication for rehospitalization. Careful outpatient follow-up of TTS patients may be warranted to avoid readmissions.
| S-EPMC6440439 | biostudies-literature
Project description: Not available
| S-EPMC10243999 | biostudies-literature