RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts.

Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial.

Prognostic modelling of clinical outcomes after first-time acute coronary syndrome in New Zealand.

Objective: The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) was established to investigate the drivers of secondary events after first-time acute coronary syndrome (ACS), including addressing inequitable outcomes by ethnicity. Herein, the first clinical outcomes and prognostic modelling approach are reported.

Methods: First, in 28 176 New Zealanders with first-time ACS from a national registry, a clinical summary score for predicting 1-year death/cardiovascular readmission was created using Cox regression of 20 clinical variables.

Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure.

Background: Multi-omics delivers more biological insight than targeted investigations. We applied multi-omics to patients with heart failure with reduced ejection fraction (HFrEF).

Methods: 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography mass spectrometry (LC-MS/GC-MS) and solid-phase microextraction (SPME) volatilomics in plasma and urine.

A machine learning PROGRAM to identify COVID-19 and other diseases from hematology data.

Aim: We propose a method for screening full blood count metadata for evidence of communicable and noncommunicable diseases using machine learning (ML).

Materials & Methods: High dimensional hematology metadata was extracted over an 11-month period from Sysmex hematology analyzers from 43,761 patients. Predictive models for age, sex and individuality were developed to demonstrate the personalized nature of hematology data.

Multiomics, virtual reality and artificial intelligence in heart failure.

Multiomics delivers more biological insight than targeted investigations. We applied multiomics to patients with heart failure (HF) and reduced ejection fraction (HFrEF), with machine learning applied to advanced ECG (AECG) and echocardiography artificial intelligence (Echo AI). In total, 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography-mass spectrometry and solid-phase microextraction volatilomics in plasma and urine.

Afterdepolarizations and abnormal calcium handling in atrial myocytes with modulated SERCA uptake: a sensitivity analysis of calcium handling channels.

Delayed afterdepolarizations (DADs) and spontaneous depolarizations (SDs) are typically triggered by spontaneous diastolic Ca release from the sarcoplasmic reticulum (SR) which is caused by an elevated SR Ca-ATPase (SERCA) uptake and dysfunctional ryanodine receptors. However, recent studies on the T-box transcription factor gene (TBX5) demonstrated that abnormal depolarizations could occur despite a reduced SERCA uptake. Similar findings have also been reported in experimental or clinical studies of diabetes and heart failure.

In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a major cause of stroke and morbidity. Recent genome-wide association studies have shown that paired-like homeodomain transcription factor 2 (Pitx2) to be strongly associated with AF. However, the mechanisms underlying Pitx2 modulated arrhythmogenesis and variable effectiveness of antiarrhythmic drugs (AADs) in patients in the presence or absence of impaired Pitx2 expression remain unclear.

Polygenic Risk Scores in Coronary Artery Disease and Atrial Fibrillation.

Coronary artery disease (CAD) and atrial fibrillation (AF) are two highly prevalent cardiovascular disorders that are associated with substantial morbidity and mortality. Conventional clinical risk factors for these disorders may not be identified prior to mid-adult life when pathophysiological processes are already established. A better understanding of the genetic underpinnings of disease should facilitate early detection of individuals at risk and preventative intervention.

A multiplex pharmacogenetics assay using the MinION nanopore sequencing device.

Objectives: The MinION nanopore sequencing device opens the opportunity to cost-effective and point-of-care DNA sequencing. As a proof of principle, we developed a multiplex assay targeting pharmacogenetic variants related to clopidogrel and warfarin, the two commonly used drugs that show response variability due to genetic polymorphisms.

Methods: Six reference and 78 clinical DNA samples were amplified by PCR to generate 15 amplicons targeting 27 key variants.

Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells.

Transcription factors TBX5 and PITX2 involve in the regulation of gene expression of ion channels and are closely associated with atrial fibrillation (AF), the most common cardiac arrhythmia in developed countries. The exact cellular and molecular mechanisms underlying the increased susceptibility to AF in patients with TBX5/PITX2 insufficiency remain unclear. In this study, we have developed and validated a novel human left atrial cellular model (TPA) based on the ten Tusscher-Panfilov ventricular cell model to systematically investigate how electrical remodeling induced by TBX5/PITX2 insufficiency leads to AF.

A Machine Learning Aided Systematic Review and Meta-Analysis of the Relative Risk of Atrial Fibrillation in Patients With Diabetes Mellitus.

Meta-analysis is a widely used tool in which weighted information from multiple similar studies is aggregated to increase statistical power. However, the exponential growth of publications in key areas of medical science has rendered manual identification of relevant studies increasingly time-consuming. The aim of this work was to develop a machine learning technique capable of robust automatic study selection for meta-analysis.

Personalized hypertension management in practice.

The revolution occurring in genomic and personalized medicine is likely to have a significant impact on the management of hypertension. However, from the perspective of translating new knowledge into clinical practice, progress has been slow. This review article summarizes recent advances in hypertension-related diagnostics while also offering new perspective on hypertension management for the future.

ICMA: an integrated cardiac modeling and analysis platform.

Unlabelled: ICMA, a software framework to create 3D finite element models of the left ventricle from cardiac ultrasound or magnetic resonance imaging (MRI) data, has been made available as an open-source code. The framework is hardware vendor independent and uses speckle tracking (endocardial border detection) on ultrasound (MRI) imaging data in the form of DICOM. Standard American Heart Association segment-based strain analysis can be performed using a browser-based interface.

Open access integrated therapeutic and diagnostic platforms for personalized cardiovascular medicine.

It is undeniable that the increasing costs in healthcare are a concern. Although technological advancements have been made in healthcare systems, the return on investment made by governments and payers has been poor. The current model of care is unsustainable and is due for an upgrade.

The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers.

Patients with cardiovascular disease taking aspirin and some nonsteroidal anti-inflammatory drugs (NSAIDs) appear to have increased vascular events. This study was conducted to compare the ex vivo antiplatelet effects of 6 commonly used NSAIDs and to determine whether these agents antagonize the effect of aspirin. Platelet function was assessed by Platelet Function Analyzer 100 closure time in normal subjects in a randomized, blinded, multiple-crossover study.