R Citro

Role of echocardiography in takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is characterized by transient and reversible left ventricular (LV) systolic dysfunction due to extended myocardial stunning. Despite a good long term prognosis, approximately one-third of patients with TTC experience life-threatening complications during the acute phase. Echocardiography is the first imaging modality for an early evaluation of LV systolic and diastolic function in patients with TTC. Moreover, echocardiography allows the detection of specific findings associated with TTC, such as LV outflow tract obstruction, mitral regurgitation, and right ventricular involvement, providing crucial information for clinical management and therapy and for monitoring myocardial function recovery during the follow-up.

A novel miR-371a-5p-mediated pathway, leading to BAG3 upregulation in cardiomyocytes in response to epinephrine, is lost in Takotsubo cardiomyopathy

Molecular mechanisms protecting cardiomyocytes from stress-induced death, including tension stress, are essential for cardiac physiology and defects in these protective mechanisms can result in pathological alterations. Bcl2-associated athanogene 3 (BAG3) is expressed in cardiomyocytes and is a component of the chaperone-assisted autophagy pathway, essential for homeostasis of mechanically altered cells. BAG3 ablation in mice results in a lethal cardiomyopathy soon after birth and mutations of this gene have been associated with different cardiomyopathies including stress-induced Takotsubo cardiomyopathy (TTC). The pathogenic mechanism leading to TTC has not been defined, but it has been suggested that the heart can be damaged by excessive epinephrine (epi) spillover in the absence of a protective mechanism. The aim of this study was to provide more evidence for a role of BAG3 in the pathogenesis of TTC. Therefore, we sequenced BAG3 gene in 70 TTC patients and in 81 healthy donors with the absence of evaluable cardiovascular disease. Mutations and polymorphisms detected in the BAG3 gene included a frequent nucleotide change g2252c in the BAG3 3′-untranslated region (3′-UTR) of Takotsubo patients (P<0.05), resulting in loss of binding of microRNA-371a-5p (miR-371a-5p) as evidenced by dual-luciferase reporter assays and argonaute RNA-induced silencing complex catalytic component 2/pull-down assays. Moreover, we describe a novel signaling pathway in cardiomyocytes that leads to BAG3 upregulation on exposure to epi through an ERK-dependent upregulation of miR-371a-5p. In conclusion, the presence of a g2252c polymorphism in the BAG3 3′-UTR determines loss of miR-371a-5p binding and results in an altered response to epi, potentially representing a new molecular mechanism that contributes to TTC pathogenesis.

Global longitudinal strain predicts outcome after MitraClip implantation for secondary mitral regurgitation

Aim The aim of this study was to assess preoperative determinants, prevalence, and prognostic impact of left ventricular (LV) reverse remodeling (LVRR) in patients with secondary mitral regurgitation (SMR), undergoing MitraClip implantation (MCi). Methods From March 2012 to January 2015, a total of 41 consecutive patients with moderate-to-severe SMR treated successfully with MCi were enrolled. All patients underwent clinical and echocardiographic follow-up after MCi. Global longitudinal strain (GLS) was obtained using two dimensional speckle tracking analysis. A reduction in LV end-systolic volume more than 10% compared with baseline was considered as a marker of LVRR. Patients were divided into two groups according to the presence or absence of LVRR. Cardiac events were defined as the occurrence of cardiac death, rehospitalization for worsening heart failure, and mitral valve surgery. Results On univariable analysis, EuroSCORE II and GLS were associated with LVRR. On multivariable logistic regression analysis, GLS was the only independent correlate of LVRR (P = 0.004). A receiver operating characteristic curve identified a cutoff value for GLS of −9.25% (P < 0.001) associated with LVRR, with a sensitivity and specificity of 81 and 74%, respectively. New York Heart Failure Association class more than 2 after MCi, absence of LVRR after MCi, and preoperative GLS more than −9.25% were significantly correlated with adverse cardiac events at long-term follow-up. On multivariable logistic regression analysis, GLS was the only independent predictor of composite adverse cardiac events at 2-year follow-up. Conclusion A worse preoperative GLS predicts no LVRR and is associated with adverse long-term outcome after successful MCi for SMR.