Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1) caused by cardiac ryanodine receptor (RyR2) gene mutations resulting in abnormal calcium release from sarcoplasmic reticulum. Dantrolene, an inhibitor of Ca2+ release, has been shown to rescue this vitro. We assessed the antiarrhythmic efficacy dantrolene six patients carrying various RyR2 causing CPVT. The underwent exercise stress test before and after...

Serum lipid concentrations, relative body weight, and smoking habits were assessed in a cohort of 1648 middle-aged Finnish men who subsequently followed for seven years. Multivariate analysis showed that serum triglyceride cholesterol concentrations all independently associated with cardiovascular mortality. High increased the risk death only when they exceeded 1.7 mmol/l (150 mg/100 ml), but this occurred at weight levels. Obesity influenced rates raised levels, while was mortality any...

The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or preliminary cardiotoxicity tests, generated better understanding hiPSC-CM biophysical mechanisms great amount action potential calcium transient data. In this paper, we propose a new in silico model, with particular attention to Ca2+ handling. We used i) the Paci2013 model starting point, ii)...

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have revolutionized cardiovascular research. Abnormalities in Ca

Abstract Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer an attractive experimental platform to investigate cardiac diseases and therapeutic outcome. In this study, iPSC-CMs were utilized study their calcium transient signals drug effects by means of machine learning, a central part artificial intelligence. Drug assessed in six iPSC-lines carrying different mutations causing catecholaminergic polymorphic ventricular tachycardia (CPVT), highly malignant...

Abstract Cardiovascular diseases remain as the most common cause of death worldwide. To reveal underlying mechanisms in varying cardiovascular diseases, vitro models with cells and supportive biomaterial can be designed to recapitulate essential components human heart. In this study, we analyzed whether 3D co-culture cardiomyocytes (CM) vascular network adipose tissue-derived mesenchymal stem/stromal (ASC) support CM functionality. were cultured either endothelial (EC) ASC or only...

Long QT syndrome (LQTS) is associated with increased risk of ventricular arrhythmias and cardiac arrest. LQTS type 1 (LQT1), the most prevalent subtype LQTS, caused by defects slow delayed rectifier potassium current (IKs) that lead to abnormal repolarization. Here we used pluripotent stem cell (iPSC)-technology investigate both electrophysiological also for first time mechanical beating behavior genetically defined, LQT1 specific cardiomyocytes (CMs) carrying different mutations.We...

In the present research we tackled classification of seven genetic cardiac diseases and control subjects by using an extensive set machine learning algorithms with their variations from simple K-nearest neighbor searching method to support vector machines. The was based on calcium transient signals measured induced pluripotent stem cell-derived cardiomyocytes. All in all, 55 different alternatives were used model eight classes applying principle 10-fold crossvalidation peak data 1626...

Mutations in the HERG gene encoding potassium ion channel HERG, represent one of most frequent causes long QT syndrome type-2 (LQT2). The same genetic mutation frequently presents different clinical phenotypes family. Our study aimed to model LQT2 and functional differences between carriers variable phenotypes. We derived human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) from asymptomatic symptomatic When comparing single hiPSC-CMs, results allelic imbalance, current...

Ischemic heart disease (IHD) is one of the leading causes mortality worldwide. Preserving functionality and preventing arrhythmias are key principles in management patients with IHD. Levosimendan, a unique calcium (Ca2+) enhancer inotropic activity, has been introduced into clinical usage for failure treatment. Human-induced pluripotent cell-derived cardiomyocytes (hiPSC-CMs) offer an opportunity to better understand pathophysiological mechanisms as well serve platform drug screening. Here,...

Mutations in the cardiac ryanodine receptor (RYR2) are leading cause for catecholaminergic polymorphic ventricular tachycardia (CPVT). In this study, we evaluated antiarrhythmic efficacy of carvedilol and flecainide CPVT patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying different mutations RYR2. iPSC-CMs were generated from skin biopsies patients exon 3 deletion L4115 or V4653F mutation RYR2 a healthy individual. Ca 2+ kinetics drug effects studied...

In order to translate preclinical data into the clinical studies, relevant in vitro models with structure and key functional properties similar native human tissue should be used. cardiac vascular structures mimic highly vascularized myocardium provide interactions between endothelial cells, stromal cells cardiomyocytes. Currently, pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been shown present immature morphology fetal-like electrophysiological that may limit their use as...

Spontaneous Ca2+ release leads to afterdepolarizations and triggered arrhythmia in catecholaminergic polymorphic ventricular tachycardia (CPVT). Irregular is hypothesized manifest as slowed depolarization irregular repolarization. Our goal was study repolarization abnormalities CPVT, they remain largely uninvestigated.We studied intracellular handling action potentials (APs) an induced pluripotent stem cell (iPSC) model of CPVT. Induced cardiomyocytes from a RyR2-P2328S patient showed...

Comprehensive functioning of Ca2+ cycling is crucial for excitation–contraction coupling cardiomyocytes (CMs). Abnormal linked to arrhythmogenesis, which associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived patients catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited severe disease. studies revealed substantial abnormalities in these CMs. transient analysis...

Abstract Background Modeling human cardiac diseases with induced pluripotent stem cells not only enables to study disease pathophysiology and develop therapies but also, as we have previously showed, it can offer a tool for diagnostics. We observed that few genetic be separated from each other healthy controls by applying machine learning Ca2+ transient signals measured iPSC-derived cardiomyocytes (CMs). Objectives For the current research, 419 hypertrophic cardiomyopathy (HCM) 228 long QT...

Brugada syndrome is an inherited cardiac arrhythmia disorder that mainly associated with mutations of the voltage-gated sodium channel alpha subunit 5 (SCN5A) gene. The clinical symptoms include ventricular fibrillation and increased risk sudden death. Human-induced pluripotent stem cell (hiPSC) lines were derived from symptomatic asymptomatic individuals carrying R1913C mutation in SCN5A present work aimed to observe phenotype-specific differences hiPSC-derived cardiomyocytes (CMs) obtained...

Induced pluripotent stem cell (iPSC) lines derived from skin fibroblasts of patients suffering cardiac disorders were differentiated to cardiomyocytes and used generate a data set Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> transients 136 recordings. The objective was separate normal signals for later medical research abnormal signals. We constructed signal analysis procedure detect peaks representing calcium cycling in another...

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been shown to be useful improve techniques that are developed for the study of cardiac disease. Abnormalities in Ca2+ transients commonly present iPSC-CMs derived from individuals with a We previously observed transient signals healthy CMs can distinguished having different genetic diseases. Machine learning was used distinguish diseases each other as well controls. wanted further investigate whether we able separate...

In this preliminary research we examine the suitability of hierarchical strategies multi-class support vector machines for classification induced pluripotent stem cell (iPSC) colony images. The iPSC technology gives incredible possibilities safe and patient specific drug therapy without any ethical problems. However, growing iPSCs is a sensitive process abnormalities may occur during process. These need to be recognized problem returns image classification. We have collection 80 images where...

Cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs) can be used to study genetic cardiac diseases. In patients these diseases are manifested e.g. with impaired contractility and fatal arrhythmias, both of due abnormal calcium transients in cardiomyocytes. Here we classify different using Ca2+ transient data machine learning algorithms. By studying cycling disease-specific iPSC-CMs by measured it is possible each other also healthy controls applying computation...

We often encounter experimental results that are difficult to quantify although the visual recognition of a phenomenon is apparent. able detect patterns and features with our vision complex specify algorithmically. This because brain has evolved into powerful pattern matching machine. One important class measurement in medical research signals describe cycling some phenomenon. In this work, we developed software tool, Anomaly Explorer, assist classification Ca <sup...