Rationale and design of the rigorous atrial analysis in advanced interatrial block (ARABIA) prospective study.

BACKGROUND: Advanced interatrial block (IAB) is present in 10% of subjects ≥75 years and is associated with the risk of clinical events. METHODS AND RESULTS: Prospective multicenter study that will include subjects ≥75 years without exclusion criteria (indication for anticoagulation, cardiac devices, severe valve disease, systolic dysfunction, moderate or severe cognitive impairment, poor echocardiographic window, non-sinus rhythm or partial IAB, stroke, and life expectancy <2 years). A total of 356 subjects, 178 patients with advanced IAB (exposed) and 178 matched individuals with normal P-wave (non-exposed) will be included. Electrocardiogram and advanced transthoracic echocardiography will be performed. Two substudies will include magnetic resonance imaging: cardiac (86 subjects, 43 exposed, and 43 non-exposed) and brain (86 subjects, 43 exposed, and 43 non-exposed). The follow-up will be 2 years. Our main objective is to determine the association of advanced IAB, P-wave duration, and atrial imaging parameters (I] atrial global longitudinal strain, II] maximal left atrial volume index, III] left atrial ejection fraction, IV] left atrial fibrosis - % total left atrial area V] inter- and intra-atrial asynchrony/dyssynchrony) with clinical events (atrial fibrillation, stroke, cognitive impairment, and mortality). The secondary objective is to assess the association of the P-wave duration with atrial imaging parameters and of both with cerebral microemboli in magnetic resonance imaging. CONCLUSION: Our study will provide data regarding the association of advanced IAB, P-wave duration, and atrial imaging parameters with clinical events. We will also assess the association P-wave duration-atrial imaging parameters-cerebral microemboli.

[Peripheral arterial thromboembolism in Crohn's disease]. / Tromboembolia arterial periférica en enfermedad de Crohn.

INTRODUCTION: Inflammatory Bowel Disease (IBD) usually affects the gastrointestinal tract, although some patients can also develop extraintestinal manifestations, such as vascular symptoms both venous and arterial ones. The former being more frequent than the latter. CLINICAL REPORT: We report the case of a 62-year-old male, diagnosed of Crohns disease (CD) (A3,L1+L4,B3), admitted to hospital for treatment of a retroperitoneal abscess. He presented a peripheral arterial thromboembolism during his stay, which required urgent embolectomy. After anticoagulation with low-molecular-weight heparin (LMWH), vascular magnetic resonance imaging revealed a large thrombus involving the descent aorta, which was solved with surgery and long-term anticoagulation. CONCLUSION: Peripheral arterial thrombosis is a rare extraintestinal manifestation of IBD. Nevertheless it is always important to consider it in patients with IBD. Prophylactic treatment should be made with low-molecular-weight heparin (LMWH) and definitive treatment with a combination of LMWH and surgery.

Cardiac Allograft Rejection Induces Changes in Nucleocytoplasmic Transport: RANGAP1 as a Potential Non-Invasive Biomarker.

The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61-105.69) vs. 35.33 ng/mL (IQR, 19.18-64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.

Ranolazine as an Alternative Therapy to Flecainide for SCN5A V411M Long QT Syndrome Type 3 Patients.

The prolongation of the QT interval represents the main feature of the long QT syndrome (LQTS), a life-threatening genetic disease. The heterozygous SCN5A V411M mutation of the human sodium channel leads to a LQTS type 3 with severe proarrhythmic effects due to an increase in the late component of the sodium current (INaL). The two sodium blockers flecainide and ranolazine are equally recommended by the current 2015 ESC guidelines to treat patients with LQTS type 3 and persistently prolonged QT intervals. However, awareness of pro-arrhythmic effects of flecainide in LQTS type 3 patients arose upon the study of the SCN5A E1784K mutation. Regarding SCN5A V411M individuals, flecainide showed good results albeit in a reduced number of patients and no evidence supporting the use of ranolazine has ever been released. Therefore, we ought to compare the effect of ranolazine and flecainide in a SCN5A V411M model using an in-silico modeling and simulation approach. We collected clinical data of four patients. Then, we fitted four Markovian models of the human sodium current (INa) to experimental and clinical data. Two of them correspond to the wild type and the heterozygous SCN5A V411M scenarios, and the other two mimic the effects of flecainide and ranolazine on INa. Next, we inserted them into three isolated cell action potential (AP) models for endocardial, midmyocardial and epicardial cells and in a one-dimensional tissue model. The SCN5A V411M mutation produced a 15.9% APD90 prolongation in the isolated endocardial cell model, which corresponded to a 14.3% of the QT interval prolongation in a one-dimensional strand model, in keeping with clinical observations. Although with different underlying mechanisms, flecainide and ranolazine partially countered this prolongation at the isolated endocardial model by reducing the APD90 by 8.7 and 4.3%, and the QT interval by 7.2 and 3.2%, respectively. While flecainide specifically targeted the mutation-induced increase in peak INaL, ranolazine reduced it during the entire AP. Our simulations also suggest that ranolazine could prevent early afterdepolarizations triggered by the SCN5A V411M mutation during bradycardia, as flecainide. We conclude that ranolazine could be used to treat SCN5A V411M patients, specifically when flecainide is contraindicated.

Amyloid cardiomyopathy: a hidden heart failure cause that is often misdiagnosed.

BACKGROUND: Congestive heart failure (CHF) is a very common condition, especially in the elderly, characterized by dyspnea, orthopnea, nocturnal paroxysmal dyspnea, and peripheral edema. CLINICAL PRESENTATION AND INTERVENTION: We report the case of a 76-year-old with CHF symptoms for the last 3 months. The ECG and transthoracic echocardiogram were suggestive of CHF due to amyloid cardiomyopathy. After cardiac MRI, a positive Congo red staining of subcutaneous fat aspiration and a negative genetic testing for mutant transthyretin, senile amyloid cardiomyopathy (ATTRw) was expected. CONCLUSION: Cardiac amyloidosis is remarkably underdiagnosed. Mostly, the treatment is supportive and differs from other typical causes of CHF, and thus, a high index of suspicion is required.