Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial.

INTRODUCTION: Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. METHODS AND ANALYSIS: The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months. PRIMARY OBJECTIVE: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). SECONDARY OBJECTIVES: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. ETHICS AND DISSEMINATION: This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP)) requirements, ethical principles of the Declaration of Helsinki and national laws. The results will be submitted to indexed medical journals and national and international meetings. TRIAL REGISTRATION NUMBER: NCT02548364; Pre-results.

Two-dimensional echocardiographic features of the inferior right atrial isthmus: the role of vestibular thickness in catheter ablation of atrial flutter.

OBJECTIVES: The aim of this study was to examine the feasibility of transthoracic two-dimensional (2D)-echocardiography in defining the cavo-tricuspid isthmus (CTI) anatomy and its value concerning the ease of catheter ablation of isthmic atrial flutter (AF). METHODS: CTI analysis was accomplished in 39 cases: 16 necropsy specimens and 23 patients. Sixteen were patients with isthmus-dependent AF and seven controls with other supraventricular re-entrant tachycardias. Two-dimensional transthoracic echocardiography and a right atrium angiogram were performed before radiofrequency catheter ablation (RFCA). RESULTS: The measurements of the CTI with angiography were compared with those taken with echocardiography and correlation was excellent (r= 0.91; P < 0.0001). In normal patients, the dimension of the vestibular thickness was successfully compared and validated with the histological examination of the necropsy specimens: histology median 6.8 mm, range 4.4-10.5 vs. echo median 6.2 mm, range 5.4-8.7; P: NS. Vestibular thickness was greater in complex than in simple RFCA (13.6 ± 1.9 mm vs. 10.0 ± 2.3 mm; P = 0.01). When vestibular thickness ≥11.5 mm, the ablation prone to be complex (sensitivity 83.3%, specificity 80%, positive predictive value 71.4%, and negative predictive value 88.9%). CONCLUSIONS: Two-dimensional transthoracic echocardiography clearly depicts the inferior isthmus and, displaying the thickness of the tricuspid vestibule, it was related with complexity of the ablation procedure in isthmus-dependent AF.

Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes.

BACKGROUND: The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. METHODS AND RESULTS: Seven patients (4 men; age, 38+/-7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12+/-6 minutes of radiofrequency applications. During a follow-up of 17+/-17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. CONCLUSIONS: Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.