The role of early cardiac resynchronization therapy implantation in dilated cardiomyopathy patients with narrow QRS carrying lamin A/C mutation.

Background: Dilated cardiomyopathy (DCM) caused by Lamin A/C gene (LMNA) mutation is complicated with atrioventricular conduction disturbances, malignant ventricular arrhythmias and progressive severe heart failure.

Objective: We hypothesized that early cardiac resynchronization therapy (CRT) implantation in LMNA mutation carriers with an established indication for pacemaker or implantable cardioverter defibrillator (ICD), may preserve ejection fraction, and delay disease progression to end stage heart failure.

Methods: We compared the primary outcomes: time to heart transplantation, death due to end stage heart failure or ventricular tachycardia (VT) ablation and secondary outcomes: change in left ventricular ejection fraction (EF) and ventricular arrhythmia burden between LMNA DCM patients in the early CRT and non-CRT groups.

Clinical management of conduction abnormalities following transcatheter aortic valve replacement: prospective evaluation of a standardized management pathway.

Purpose: Limited evidence guides management of conduction abnormalities following TAVR. Standardized clinical pathways may reduce variability in care while minimizing bradyarrhythmic morbidity, length of stay (LOS), and pacemaker (PPM) implantation rates.

Methods: A multidisciplinary consensus pathway to standardize post-TAVR management was developed.

[SYNCOPE CAUSED BY INTRA-OCULAR TIMOLOL].

Introduction: Timolol eye-drops are commonly used for the treatment of glaucoma. Despite being topically applied, some systemic absorption occurs with the resulting adverse reactions related to its beta-adrenoreceptor blocking activity

Case Presentation: We report the case of a 68 years old healthy male who was admitted to our department for further workup following two episodes of syncope. Medical history taking revealed that the episodes of syncope occurred soon after beginning treatment with intra-ocular timolol for glaucoma.

From hypomagnesaemia to Zollinger-Ellison syndrome: an adverse effect of a proton pump inhibitor.

We describe the case of a 53-year-old man who presented with abdominal pain, diarrhoea and hypomagnesaemia. The hypomagnesaemia proved to be due to gastrointestinal loss as urinary fractional excretion was very low, suggesting non-renal loss. Common causes were discarded and the hypomagnesaemia was attributed to chronic use of the proton pump inhibitor, omeprazole.

Pre-operative systolic anterior motion of the mitral valve in a patient undergoing mitral valve repair.

A patient with myxomatous mitral valve prolapse underwent mitral mitral valve repair due to severe symptomatic mitral regurgitation. Preoperative echocardiography demonstrated systolic anterior motion of the mitral valve. This finding disappeared once spontaneous chordal rupture occurred, resulting in a flail posterior mitral leaflet.

Fluid loss, venous congestion, and worsening renal function in acute decompensated heart failure.

Aims: To investigate the relationship between decongestion, central venous pressure, and risk of worsening renal function (WRF) in patients with acute decompensated heart failure (ADHF).

Methods And Results: We studied 475 patients with ADHF, of whom 238 underwent right heart catheterization. Right atrial pressure (RAP) was measured at baseline and at 24 h.

Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation.

Parkinson disease (PD) is characterized by the presence of ubiquitylated inclusions and the death of dopaminergic neurons. Seven in absentia homolog (SIAH) is a ubiquitin-ligase that ubiquitylates alpha-synuclein and synphilin-1 and is present in Lewy bodies of PD patients. Understanding the mechanisms that regulate the ubiquitylation of PD-related proteins might shed light on the events involved in the formation of Lewy bodies and death of neurons.

Synphilin isoforms and the search for a cellular model of lewy body formation in Parkinson's disease.

A common finding in many neurodegenerative diseases is the presence of inclusion bodies made of aggregated proteins in neurons of affected brain regions. In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein. Although many studies have suggested that inclusion bodies may be cell protective, it is still not clear whether Lewy bodies promote or inhibit dopaminergic cell death in Parkinson's disease.

Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients.

alpha-Synucleinopathies are a group of neurological disorders characterized by the presence of intracellular inclusion bodies containing alpha-synuclein. We previously demonstrated that synphilin-1 interacts with alpha-synuclein, implying a role in Parkinson's disease. We now report the identification and characterization of synphilin-1A, an isoform of synphilin-1, which has enhanced aggregatory properties and causes neurotoxicity.

Glycogen synthase kinase 3beta modulates synphilin-1 ubiquitylation and cellular inclusion formation by SIAH: implications for proteasomal function and Lewy body formation.

alpha-Synuclein is known to play a major role in the pathogenesis of Parkinson disease. We previously identified synphilin-1 as an alpha-synuclein-interacting protein and more recently found that synphilin-1 also interacts with the E3 ubiquitin ligases SIAH-1 and SIAH-2. SIAH proteins ubiquitylate synphilin-1 and promote its degradation through the ubiquitin proteasome system.

Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by Lewy body formation and death of dopaminergic neurons. Mutations in alpha-synuclein and parkin cause familial forms of PD. Synphilin-1 was shown to interact with alpha-synuclein and to promote the formation of cytosolic inclusions.