Angelo Silverio

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.

Kocuria kristinae endocarditis related to diabetic foot infection

We report an unusual case of endocarditis occurring in a 74-year-old man with a history of systemic hypertension, diabetes mellitus and minor amputation for left forefoot ulcer. The patient was hospitalized for vacuum-assisted closure therapy to aid in wound healing. After the first treatment session, the patient reported abdominal pain with haematemesis and fever (40 °C). Owing to persistent fever, three blood cultures were performed, all positive for Kocuria kristinae. The identification was based on biochemical tests and automated systems. The speciation of the micro-organism was achieved with MALDI-TOF and then confirmed by 16S rRNA gene sequencing. Transthoracic echocardiographic examination showed the presence of a large vegetation (38×20 mm) on the posterior mitral leaflet and moderate mitral regurgitation. Since there are no current guidelines for the treatment of K. kristinae endocarditis, empiric antibiotic therapy with intravenous sulbactam/ampicillin (1.5 g twice daily) and gentamicin (6 mg kg(-1) per day) was started. After 7 days of hospitalization, the patients condition suddenly worsened because of the occurrence of haemorrhagic stroke. Despite inotropic support and rifampicin infusion, the haemodynamic status progressively deteriorated. After an initial improvement, he worsened again, becoming stuporous, hypotensive and dyspnoeic. In the following days, the patient developed compartment syndrome resulting in right foot ischaemia. Unfortunately, 25 days after hospitalization, the patient died of multiple organ failure from overwhelming sepsis. To the best of our knowledge, this is the first case of K. kristinae endocarditis on a native valve that is not related to a central venous catheter but associated with diabetic foot infection.

Polymorphisms of the antiapoptotic protein bag3 may play a role in the pathogenesis of tako-tsubo cardiomyopathy

following classes this dependence progressively increased up to the extremely high level in hrv7 class. Thiswaywe have obtained a set of HRV indiceswhich are associated in different extent with HR. Such parameters constitute a perfect material for investigations of the HR contribution to the HRV prognostic power [5]. Moreover, this may be applied not only to the spectral HRV analysis but also to any other analysis of heart rate dynamics which parameters are associated with HR — in such instances the RR-interval tachograms should rather be modified (i.e. divided or multiplied by avRRs) before a given heart rate dynamics is analyzed. Importantly, if one calculates average HRV indices from the indices corresponding to short RR interval segments (e.g. from Holter recordings), one should first obtain the global average HRV indices of all RR interval segments and then divide or multiply them by a global avRR — the division or multiplication for each segment separately may create the situation where a single RR interval segment with unusually slow or fast HR determines the results for a given patient (it is especially likely if one employs high powers of avRR). To conclude, the described approach opens new perspectives for the analysis of HR dynamics, i.e. it makes possible to separate clinical (e.g. prognostic) information coming from average heart rate and from its dynamics.

Independent Impact of RV Involvement on In-Hospital Outcome of Patients With Takotsubo Syndrome

Takotsubo syndrome (TTS) is an acute clinical condition characterized by transient left ventricular dysfunction and reversible heart failure, the pathogenetic mechanism of which remains unclear. Although left ventricular apical ballooning is the most frequent morphological pattern, other variant

Contemporary Imaging in Takotsubo Syndrome

Transthoracic echocardiography is the first-line imaging modality for evaluating patients with Takotsubo syndrome (TTS). Beyond diagnosis, TTE enables detection of peculiar complications and is useful for risk stratification and management of patients with cardiogenic shock. Cardiac magnetic resonance can be used to detect myocardial edema typically associated with TTS and is helpful in the differential diagnosis with other disease states. Coronary computed tomography angiography can be performed as an alternative to coronary angiography to confirm coronary artery patency. Molecular imaging is a promising approach for identifying patients at increased risk of recurrence.

Aortic dissection in patients with autosomal dominant polycystic kidney disease: a series of two cases and a review of the literature.

Aortic dissection (AD) is the most common life‐threatening disease involving the aorta. It is rarely associated with systemic disorders such as Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetic syndrome characterized by cystic degeneration of kidneys, possible presence of cysts in other organs and extra‐renal manifestations, including cardiovascular disorders. We performed a systematic literature search focused on the occurrence of AD associated with ADPKD (25 cases identified), and reported two cases from our experience. We selected data on sex, age, family history of ADPKD and/or AD, habitus, hypertension, renal function, presence of hepatic/pancreatic/splenic cysts, clinical presentation of AD, AD type according to the Stanford classification, treatment and outcome. Furthermore we compared this dataset with the data of the overall population with AD from the International Registry of Acute Aortic Dissection (IRAD). Stanford A type AD was documented in 62% of patients. As expected, the initial manifestation of AD was most commonly chest and back pain (80%). The mean age of AD occurrence appears significantly reduced in ADPKD patients compared to the general population with AD (49 ± 12 vs 62 ± 14, P < 0.001). Of note, our analysis shows a remarkably higher frequency of hypertension (90%) compared to the overall AD population (75%), although not significantly (P = 0.133). AD should be always ruled out in ADPKD subjects with chest and back pain symptoms, despite them being young and at lower risk. A careful preventive monitoring as well as an optimal blood pressure control may reduce the risk of AD and improve the outcome of these patients.

Risk stratification using the CHA2DS2-VASc score in Takotsubo syndrome: Data from the Takotsubo Italian network

Background The CHA2DS2‐VASc score predicts stroke in patients with atrial fibrillation and has been reported to have a prognostic role even in acute coronary syndrome patients. The Takotsubo syndrome is a condition that mimics acute coronary syndrome and may present several complications including stroke. We sought to assess the ability of CHA2DS2‐VASc score to predict adverse events in Takotsubo syndrome patients. Methods and Results Overall, 371 Takotsubo syndrome patients were enrolled in a prospective registry. Patients were divided into 3 groups according to the CHA2DS2‐VASc score: Group A (≤1), B (2–3), and C (≥4). The median CHA2DS2‐VASc score was 3 (interquartile range: 2–4). Overall, 9%, 42%, and 49% were included in Group A, B, and C, respectively. Follow‐up length was 26±20 months. The mortality rate was 6%, 7%, and 17% in Group A, B, and C, respectively (P=0.011). The stroke rate was 3% and not different among the 3 groups. Estimated major adverse cardiac and cerebrovascular events (the composite of death, myocardial infarction, and stroke) rates in the 3 groups were 6%, 9%, and 17% in Group A, B, and C, respectively (P=0.033). The CHA2DS2‐VASc score resulted as a predictor of major adverse cardiac and cerebrovascular events (odds ratio 2.1, 95% confidence interval, 1.2–3.6; P=0.01) and all‐cause mortality (odds ratio 1.5, 95% confidence interval, 1.2–1.9; P=0.001). Conclusions In Takotsubo syndrome, the CHA2DS2‐VASc score allows prediction of cardiovascular events and mortality at long‐term follow‐up.

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.

A peculiar etiology of acute heart failure: adrenergic myocarditis

Pheochromocytoma can occur with a variety of cardiovascular signs and symptoms, and this tumor can also precipitate an acute heart failure associated with the typical clinical and instrumental findings of myocarditis. This peculiar etiology of acute myocarditis, known as “adrenergic myocarditis,” should be suspected when specific “red flags” of pheochromocytoma such as headache, palpitations, diaphoresis, hypertension, orthostatic hypotension, and left ventricular dysfunction suggesting Takotsubo syndrome are detected. In fact, its diagnosis allows a specific targeted therapy.

Meta-Analysis Comparing Outcomes After Everolimus-Eluting Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Metallic Stents in Patients with Acute Coronary Syndromes

Acute coronary syndromes (ACS) may represent an intriguing clinical scenario for implantation of bioresorbable vascular scaffold (BRS). Nevertheless, the knowledge about the performance of these devices in patients with ACS is limited. Therefore, we performed a meta-analysis of clinical studies aiming to assess the safety and efficacy of everolimus-eluting-BRS versus everolimus-eluting-metallic stents (EES) in ACS patients undergoing percutaneous coronary intervention. Six studies enrolling 2,318 patients were included and analyzed for the risk of primary safety outcome (stent or scaffold thrombosis [ST/ScT]), primary efficacy outcome (target lesion revascularisation [TLR]), and secondary outcomes (myocardial infarction, cardiac death, all-cause death). Median follow-up was 9.5 (6 to 19.5) months. Patients treated with BRS had a significantly higher risk of definite ST/ScT compared with those receiving EES (2.3% vs 1.08%, odds ratio [OR] 2.22, 95% confidence interval [CI] 1.10 to 4.45, p = 0.03, I2 = 0%). Similarly, the risk of TLR was significantly higher in the BRS compared with EES group (3.5% vs 2.5%, OR 1.79, 95% CI 1.02 to 3.16, p = 0.04, I2 = 0%). When TLRs due to thrombosis were excluded, the difference in risk estimates between the 2 groups was no longer significant (OR 1.19, 95% CI 0.48 to 2.98, p = 0.71, I2 = 25%). Risk for secondary endpoints did not differ between the 2 groups. Results were confirmed when clinical and procedural variables were tested as potential effect modifiers in the meta-regression analysis for both primary endpoints. In conclusion, compared with those receiving EES, patients with ACS treated with BRS had increased risk of definite device thrombosis and TLR at mid-term follow-up.