Observational Study of Trans-Septal Endocardial Left Ventricle Lead Implant for Effective Cardiac Resynchronization Therapy in Patients with Heart Failure and Challenging Coronary Sinus Anatomy.

Background: When conventional trans-venous CS lead placement fails, trans-septal endocardial left ventricle lead placement is an alternative technique used to capture the left ventricle endocardially; however, its use is limited due to a lack of evidence, practice uptake, and clinical trials.

Methods: In this single-center cohort study, we evaluated the efficiency of the procedure, post-procedural complication rate, rate of thromboembolic events, overall survival rate, and changes in the echocardiographic parameters, brain natriuretic peptide (BNP) level, and New York Heart Association (NYHA) class, both before and after TSLV lead implantation.

Results: The TSLV lead implant is safe and improves EF, LVEDV, LVESV, and LVIDd.

Comparative Analysis of Response to Cardiac Resynchronisation Therapy Upgrades in Patients with Implantable Cardioverter-Defibrillators and Pacemakers.

The efficacy of de novo cardiac resynchronisation therapy (CRT) in patients with heart failure (HF), left ventricular systolic dysfunction (LVSD), and a broad QRS morphology is well established. However, the optimal stage for upgrading patients with existing pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) and HF with high-burden right ventricular (RV) pacing remains uncertain. Thus, this multicentre retrospective analysis compared patients with pre-existing PPMs or ICDs who underwent CRT upgrades to investigate the appropriate stage for CRT implantation in these patients and to assess the validity of treating both PPM and ICD recipients under the same recommendation level in the current guidelines.

Cryothermal energy demonstrates shorter ablation time and lower complication rates compared with radiofrequency in surgical hybrid ablation for recurrent ventricular tachycardia.

Background: Recurrent ventricular tachycardia (VT) after prior endocardial catheter ablation(s) presents challenges in the setting of prior cardiac surgery where percutaneous epicardial access may not be feasible.

Objective: The purpose of this study was to compare the outcomes of cryothermal vs radiofrequency ablation in direct surgical epicardial access procedures.

Methods: We performed a retrospective study of consecutive surgical epicardial VT ablation cases.

Non-invasive imaging in cardiology for the generalist.

In contrast to invasive techniques, the goal of non-invasive cardiac imaging is to identify or exclude heart disease in response to a patient's clinical history of cardiac localizing symptoms. Imaging also aims to establish the risk of an individual developing future heart disease with a view to preventing major cardiovascular events such as myocardial infarction. As well as a role in risk stratification, non-invasive cardiac imaging also helps with decision making for future medical and procedural interventions.

Non-invasive phenotyping and drug testing in single cardiomyocytes or beta-cells by calcium imaging and optogenetics.

Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues.

An unusual haemoperitoneum--secondary abdominal pregnancy.

A 36-year-old amenorrhoeic patient presented with vague abdominal discomfort, and haemodynamic instability, a large haemoperitoneum was identified on transvaginal ultrasound. Ruptured tubal ectopic pregnancy was suspected. At laparotomy ruptured primary tubal ectopic pregnancy was identified, with 12-14 week secondary abdominal pregnancy implanted onto the omentum, confirmed by histopathology.

Neuroserpin polymers activate NF-kappaB by a calcium signaling pathway that is independent of the unfolded protein response.

The autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies is characterized by the accumulation of ordered polymers of mutant neuroserpin within the endoplasmic reticulum of neurones. We show here that intracellular neuroserpin polymers activate NF-kappaB by a pathway that is independent of the IRE1, ATF6, and PERK limbs of the canonical unfolded protein response but is dependent on intracellular calcium. This pathway provides a mechanism for cells to sense and react to the accumulation of folded structures of mutant serpins within the endoplasmic reticulum.

The molecular aetiology of the serpinopathies.

Members of the serine proteinase inhibitor or serpin superfamily inhibit their target proteinases by a conformational transition that involves the enzyme being translocated from the upper to the lower pole of the protein. This sophisticated mechanism is subverted by point mutations to form ordered polymers that are retained within the endoplasmic reticulum of the cell of synthesis. These polymers activate NF-kappaB and cause cytotoxicity by a pathway that is independent of the unfolded protein response.

The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB.

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is an autosomal dominant dementia that is characterized by the retention of polymers of neuroserpin as inclusions within the endoplasmic reticulum (ER) of neurons. We have developed monoclonal antibodies that detect polymerized neuroserpin and have used COS-7 cells, stably transfected PC12 cell lines and transgenic Drosophila melanogaster to characterize the cellular handling of all four mutant forms of neuroserpin that cause FENIB. We show a direct correlation between the severity of the disease-causing mutation and the accumulation of neuroserpin polymers in cell and fly models of the disease.

Expression of the serine protease inhibitor neuroserpin in cells of the human myeloid lineage.

Myeloid progenitors in the bone marrow differentiate into most of the major cell types of the immune system, including macrophages and dendritic cells. These cells play important roles in both innate and adaptive immunity. They express a number of proteases and protease inhibitors including members of the serine proteinase inhibitor or serpin superfamily.