Francesca Guastafierro

Dynamic changes of QTc interval and prognostic significance in takotsubo (stress) cardiomyopathy

Prolonged QT corrected (QTc) intervals are associated with adverse cardiovascular outcomes both in healthy and high‐risk populations. Our objective was to evaluate the QTc intervals during a takotsubo cardiomyopathy (TTC) episodes and their potential prognostic role.

Prevalence and prognostic relevance of atrial fibrillation in patients with Takotsubo syndrome

BACKGROUND Takotsubo syndrome (TTS) is associated with a considerable risk of complications during the acute phase and substantial long-term mortality rates. Concomitant atrial fibrillation may have an impact on outcome in these patients. Aim of this study was to assess the prevalence and prognostic relevance of atrial fibrillation in TTS. METHODS We performed an international, multicenter study including 387 TTS patients consecutively enrolled at 3 centers. Atrial fibrillation was defined as known history before admission or documented episodes during hospital stay. Long-term mortality was evaluated in median 2.9years after the acute event. RESULTS Atrial fibrillation was found in 97 TTS patients (25.1%) and was associated with older age (p<0.01), less emotional triggers (p=0.03), higher incidence of cardiogenic shock (p<0.01), lower left ventricular ejection fraction (p<0.01), and a prolonged hospital stay (p<0.01). Determinants of atrial fibrillation at admission (n=34 patients; 9.0%) in multivariate logistic regression analysis were age (p=0.001) and cardiogenic shock (p=0.013). Long-term mortality was significantly higher in TTS patients with as compared to patients without atrial fibrillation (35.2% versus 15.3%; hazard ratio 3.02, 95% confidence interval 1.90-4.78; p<0.001). In multivariate Cox regression analysis atrial fibrillation was identified as an independent determinant of outcome even after adjustment for clinical variables, left ventricular functional parameters (ballooning pattern, ejection fraction), and cardiogenic shock. CONCLUSIONS In TTS patients, atrial fibrillation is frequent and associated with increased long-term mortality rates. Furthermore, our study identifies atrial fibrillation as an independent predictor of outcome and a potential tool for risk stratification in TTS.

Impact of persistent ST elevation on outcome in patients with Takotsubo syndrome. Results from the GErman Italian STress Cardiomyopathy (GEIST) registry

BACKGROUND Potential predictors of clinical complications of Takotsubo syndrome (TTS) are poorly known. Persistent ST-segment elevation (PSTE) may have an impact on outcome similar as previously reported in acute coronary syndrome. The aim of this study was to assess the prevalence and prognostic relevance of PSTE in patients with TTS. METHODS Two-hundred-sixty-nine consecutive patients were enrolled in an international multicenter registry. PSTE was defined as the documentation of ST-elevation at least for the first 48h of hospitalization. Long-term mortality was evaluated in median 1.9years after the acute event. RESULTS PSTE was found in 52 TTS patients (19%). Patients with PSTE were characterized by higher admission levels of troponin-I (23±12 vs 8±49ng/L, p<0.001), experienced a longer hospitalization (10±5 vs 8±3days, p=0.02) and a higher rate of in-hospital complications (31% vs 17% p=0.03). At multivariate analysis including PSTE, age, male sex, admission ejection fraction, PSTE (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.4-13; p=0.01), age (OR 1.05; 95%CI 1.00-1.10; p=0.03) and admission ejection fraction (OR 0.93; 95%CI 0.87-0.99; p=0.02) were independent predictors of in-hospital complications. At long-term follow-up no significant differences in terms of mortality were observed between patients with and without PSTE (19% vs 15%; p=0.5). However, PSTE was a predictor of major cardiac adverse events (MACE) at follow-up (HR 2.32, 95% CI 1.02-5.31, p 0.045). CONCLUSIONS In TTS patients, PSTE is a common finding, represents an independent predictor of in-hospital complications and could be associated with MACE at follow-up.

Fenofibrate/simvastatin fixed-dose combination in the treatment of mixed dyslipidemia: safety, efficacy, and place in therapy

Lipids disorder is the principal cause of atherosclerosis and may present with several forms, according to blood lipoprotein prevalence. One of the most common forms is combined dyslipidemia, characterized by high levels of triglycerides and low level of high-density lipoprotein. Single lipid-lowering drugs may have very selective effect on lipoproteins; hence, the need to use multiple therapy against dyslipidemia. However, the risk of toxicity is a concerning issue. In this review, the effect and safety of an approved combination therapy with simvastatin plus fenofibrate are described, with an analysis of pros and cons resulting from randomized multicenter trials, meta-analyses, animal models, and case reports as well.

“Lambda-wave” ST-elevation is associated with severe prognosis in stress (takotsubo) cardiomyopathy

Persistent ST‐segment elevation in acute coronary syndrome is associated with both short and long‐term complications. By contrast, there is limited information about ST‐elevation and its evolution during takotsubo (stress) cardiomyopathy (TTC).

Left Ventricular Thrombi in Takotsubo Syndrome: Incidence, Predictors, and Management: Results From the GEIST (German Italian Stress Cardiomyopathy) Registry

Background Left ventricular (LV) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome. Methods and Results We enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long‐term follow‐up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST‐elevation (56% versus 16%; P<0.001) and higher troponin I levels (10.8±18.3 ng/mL versus 3.5±4.3 ng/mL; P=0.001) as compared with those without LV thrombi. At multivariate analysis including age, sex, LV ejection fraction, ST‐elevation at admission, and apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01–40.0; P=0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long‐term follow‐up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P=0.99). Conclusions LV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high‐risk patients.

Inflammatory patterns in Takotsubo cardiomyopathy and acute coronary syndrome: A propensity score matched analysis

BACKGROUND AND AIMS Systemic inflammatory activation can be observed in both Takotsubo cardiomyopathy (TTC) and acute coronary syndrome (ACS). The aim of this study was therefore to compare circulating cytokine levels during the acute and subacute phase of TTC and ACS. METHODS One hundred thirty-six consecutive patients were enrolled in the study; after a propensity score matching, 32 TTC patients were compared with 32 subjects with ACS. Clinical baseline features and circulating levels of interleukin(IL)-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, MCP1, EGF, VEGF, TNFα were obtained at admission (t0) and after 120 h (t1). RESULTS At t0, several circulating IL levels were higher in subjects with TTC (IL-2 2 vs. 0.5 pg/ml, IL-4 1.5 vs. 0.82 pg/ml, IL-10 3.34 vs. 1.62 pg/ml, TNF-α 5 vs. 2.3 pg/ml, IFN-γ 0.92 vs. 0.32 pg/ml, EGF 84.8 vs. 10.7 pg/ml, p < 0.05 in all cases), while IL-6 levels were higher in patients with ACS (25.4 vs. 12.4 pg/ml p = 0.03). At t1, IL-2 and EGF levels were still higher in patients with TTC vs. those with ACS (IL-2 4.6 vs. 0.72 pg/ml, p = 0.01; EGF 36.3 vs. 18.5 pg/ml, p = 0.03), while IL-6 serum levels were higher in ACS patients (19.6 vs. 7.35 pg/ml, p = 0.02). CONCLUSIONS Different inflammatory patterns can be observed during the acute and subacute phase of TTC when compared to ACS. Increased levels of anti-inflammatory interleukins can be found during the acute phase of TTC while ACS is featured by higher levels of IL-6 during the acute and sub-acute phase.