Defibrillation remains the only effective therapy against sudden cardiac death. However, the current coil-based lead ICD devices are limited by high defibrillation threshold (DFT) and low arrhythmia sensing resolution, which can result in inappropriate and painful shocks adversely affecting the quality of life. Emerging classes of materials and mechanics concepts in the field of flexible and stretchable electronics have created new opportunities for integrating high-performance electronics with the human body and its organs and various tissues. These conformal electronics devices offer a platform for high-definition arrhythmia sensing to minimize inappropriate shocks and improve therapy and high-definition therapy delivery circuit to reduce DFT.
Mitral valve prolapse (MVP) is a common valvopathy that can lead to heart failure and sudden death. However, the causes of MVP development are still poorly understood.
Functional genomic studies are needed to better characterize MVP associated variants and target genes
WHAT DOES THIS STUDY ADD?
We used ATAC-Seq (assay for transposes-accessible chromatin using sequencing) genomic annotation technique in combination with 4C-Seq (circular chromosome conformation capture, coupled to high-throughput sequencing), to describe unprecedented genome-wide chromatin profiles from human pathogenic and non-pathogenic mitral valves.
The experiments also provided evidence for plausible causal variants for rs2641440 at SMG6/SRR locus and rs6723013 at IGFBP2/IGFBP5/TNS1 locus. In addition, we also identified several target genes including SRR, HIC1, and DPH1 at SMG6/SRR locus.
Catheters are widely used for minimally invasive therapies such as atrial fibrillation ablation, intravascular stents, etc. In addition, they are also used for capturing information during procedures such as measuring temperature, pressure, electrograms etc.
However, these catheters are limited by mechanical rigidity, low spatial densities, single function capability necessitating use of multiple catheters to acquire critical information.
WHAT THIS STUDY ADDS?
We have designed a novel flexible, stretchable and tissue conforming electronics device integrated with a balloon catheter that supports simultaneous high-density spatiotemporal mapping of temperature, pressure, and electrograms.
In addition, our device allows for programmable electrical stimulation, radio frequency ablation and irreversible electroporation.
This novel device, the first of its kind, anywhere in the world, will eventually enable physicians to acquire a rich set of physiological information and complete surgeries and deliver therapies in shorter times than currently possible, with a single instrumented catheter system.
Computer models use patient specific tissue geometry and cardiac fiber orientation to generate clinically relevant simulations of human cardiac action potentials.
However, none of the models take into account tissue-specific, person-specific, and pathology-specific gene expression profiles which all are known to affect the action potential morphology and propagation dynamics.
WHAT THIS STUDY ADDS?
A novel modification of genetic algorithm which determines personalized parameters of cardiac action potential based on set of human action potentials recorded at different heart rates.
A mRNA based model that can predict action potential waveform at different heart rates with high precision and which makes it possible to map gene expression profile to cardiac function.
Preclinical studies have implicated multiple mechanisms for sustaining myocardial fibrillation
Clinical translation to guide treatment in patients with atrial fibrillation and ventricular fibrillation survival remains challenging due to poor spatial resolution of clinical mapping systems and a lack of suitable analysis tool.
WHAT THIS STUDY ADDS?
Granger causality analysis, originally an econometric tool for quantifying causal relationships between complex-time series, was developed in rat ventricular fibrillation and validated in human ventricular fibrillation and atrial fibrillation as a novel fibrillation mapping tool.
Grange causality-based fibrillation analysis can measure global fibrillation organization, characterize dominant propagating patterns, and map rotational drivers using low spatial resolution sequentially acquired data.