Treatment Of Cardiac Disorders Research Articles

Leveraging the Capabilities of AI: Novice Neurology-Trained Operators Performing Cardiac POCUS in Patients with Acute Brain Injury.

Cardiac point-of-care ultrasound (cPOCUS) can aid in the diagnosis and treatment of cardiac disorders. Such disorders can arise as complications of acute brain injury, but most neurologic intensive care unit (NICU) providers do not receive formal training in cPOCUS. Caption artificial intelligence (AI) uses a novel deep learning (DL) algorithm to guide novice cPOCUS users in obtaining diagnostic-quality cardiac images. The primary objective of this study was to determine how often NICU providers with minimal cPOCUS experience capture quality images using DL-guided cPOCUS as well as the association between DL-guided cPOCUS and change in management and time to formal echocardiograms in the NICU. From September 2020 to November 2021, neurology-trained physician assistants, residents, and fellows used DL software to perform clinically indicated cPOCUS scans in an academic tertiary NICU. Certified echocardiographers evaluated each scan independently to assess the quality of images and global interpretability of left ventricular function, right ventricular function, inferior vena cava size, and presence of pericardial effusion. Descriptive statistics with exact confidence intervals were used to calculate proportions of obtained images that were of adequate quality and that changed management. Time to first adequate cardiac images (either cPOCUS or formal echocardiography) was compared using a similar population from 2018. In 153 patients, 184 scans were performed for a total of 943 image views. Three certified echocardiographers deemed 63.4% of scans as interpretable for a qualitative assessment of left ventricular size and function, 52.6% of scans as interpretable for right ventricular size and function, 34.8% of scans as interpretable for inferior vena cava size and variability, and 47.2% of scans as interpretable for the presence of pericardial effusion. Thirty-seven percent of screening scans changed management, most commonly adjusting fluid goals (81.2%). Time to first adequate cardiac images decreased significantly from 3.1 to 1.7days (p < 0.001). With DL guidance, neurology providers with minimal to no cPOCUS training were often able to obtain diagnostic-quality cardiac images, which informed management changes and significantly decreased time to cardiac imaging.

Evaluation of Bioenhancing Effect of Piperine and its Analogs on the Pharmacokinetics of Verapamil

A present study was undertaken to understand the impact of piperine and some of its derivatives on the bioavailability of verapamil used in the treatment of cardiac disorders. On oral administration, it undergoes fast biotransformation resulting in its low bioavailability. Its bioavailability varies between 20 and 35%. Piperine (a well-known bioenhancer) has been reported to improve the bioavailability of a wide range of structurally and therapeutically varied medicines. Hence some derivatives of piperine were synthesized and evaluated for their bioenhancing effect on verapamil. The bioenhancing effect of piperine and synthesized derivatives was investigated and compared using a validated HPLC method per USFDA guidelines. The pharmacokinetic characteristics of verapamil alone and when combined with piperine and its synthetic analogs were also investigated. When administered to wistar rats, it was discovered that verapamil bioavailability was 1.54 times higher when given with piperine and 2.42 times higher when given with morpholine derivative. The study undertaken indicates that some synthetic derivatives of piperine can be successfully used to enhance the bioavailability of verapamil to a considerable extent

Cardiac biophysical detailed synergetic modality rendering and visible correlation.

The heart is a vital organ in the human body. Research and treatment for the heart have made remarkable progress, and the functional mechanisms of the heart have been simulated and rendered through the construction of relevant models. The current methods for rendering cardiac functional mechanisms only consider one type of modality, which means they cannot show how different types of modality, such as physical and physiological, work together. To realistically represent the three-dimensional synergetic biological modality of the heart, this paper proposes a WebGL-based cardiac synergetic modality rendering framework to visualize the cardiac physical volume data and present synergetic correspondence rendering of the cardiac electrophysiological modality. By constructing the biological detailed interactive histogram, users can implement local details rendering for the heart, which could reveal the cardiac biology details more clearly. We also present cardiac physical-physiological correlation visualization to explore cardiac biological association characteristics. Experimental results show that the proposed framework can provide favorable cardiac biological detailed synergetic modality rendering results in terms of both effectiveness and efficiency. Compared with existing methods, the framework can facilitate the study of the internal mechanism of the heart and subsequently deduce the process of initiation, development, and transformation from a healthy heart to an ill one, and thereby improve the diagnosis and treatment of cardiac disorders.

P6593Comparison of the termination effects between multi-segment continuous illumination and anti-tachycardia pacing on myocardial infarction ventricular arrhythmia

Abstract Introduction Anti-tachycardia pacing (ATP) therapy is an important treatment for current ICD termination of ventricular arrhythmia (VA). But there was concern about excessive frequency and voltage can cause arrhythmia, pain and damage. Optogenetic allowed modulation of electrical excitation with light in myocardium over-expressing light-sensitive protein, and optical illumination developed a non-contact and pain-free approach to research and treatment of cardiac disorder. Purpose Explore the effects of optogenetic termination and electric termination of myocardial infarction VA in vivo. Methods Rats (N=10) accepted jugular vein injection with 1×1012 vector genomes of (AAV-CAG-hChR2(H134R)-mcherry) to achieve cardiac transgenic expression of light sensitive protein Channelrhodopsin-2 (ChR2). After thoracotomy, myocardial infarction was induced by ligation of the left anterior descending coronary artery, and then VA was induced by electrical burst stimulation (10 v, 50 Hz, 2 s). Before the myocardial infarction operation, every heart was illuminated by 473 nm laser or electrical stimulated on the right ventricle in a train of 30 pulses at 8 HZ to test the threshold of light intensity or electrical pacing voltage. The VA termination process during 20 s after burst stimulation was investigated in different performance: optical termination, 1 s constant illumination repeated in 4 episodes with 1 s interval (470 nm, 20 times threshold intensity); electrical termination, ATP in 8 pulses of 8hz with 2ms duration in 4 times pacing threshold; natural recovery from VA, without optical or electrical intervention. Recovery time was defined as the time from the end of the burst stimulation to the recovery of sinus rhythm, and the termination rate was the percentage of sinus rhythm recovery among 11s after the end of burst stimulation with or without any intervention. Results We analyzed the recovery time and the termination rate (N=10, n=127 episodes per mode). The sequence of recovery time was optical termination (7.328±0.3623 s) &lt; electric termination (10.31±0.4482 s) &lt; natural recovery (12.97±0.3834 s) (figure D). We confirmed that the termination rate of optical illumination (86.14±4.145%) was higher than those of ATP (63.5±6.371%) and natural recovery (47.71±5.476%) (figure E), and there was no significant difference between the last two process (one-way of ANOVA; p=0.124). Comparison of three modes Conclusions Optogenetic manipulation shortened the recovery time and increased the termination rate in myocardial infarction ventricular arrhythmia, which may provide a potential approach for translational arrhythmia therapy. Acknowledgement/Funding The national natural science foundation of China (81772044)

Analytical Method Development and Validation for Simultaneous Estimation of Trimetazidine Hydrochloride and Metoprolol Succinate Using HPTLC

Introduction:Trimetazidine and Metoprolol combination is more effective in the treatment of cardiac disorders as compared to single drug therapy.Background:Materials and Methods:A rapid, simple, and sensitive HPTLC method was developed for the simultaneous determination of Trimetazidine and metoprolol from its tablet dosage form and validated. In HPTLC method, standard and sample solutions of Trimetazidine hydrochloride and metoprolol succinate were applied on pre-coated silica gel G 60 F254 TLC plate, and developed by using mobile phase, n-butanol :water: methanol: ammonia as solvent (8.5:0.1:0.1: 0.85, v/v). The drugs on plate were scanned at 213 nm. The method produced compact and well-resolved bands at Rf of 0.32 ± 0.02 and 0.66 ± 0.02 for Trimetazidine Hydrochloride and Metoprolol succinate respectively. The range for linearity was observed as 500-2500 ng band-1 for Trimetazidine hydrochloride and 500-2500 ng band-1 for metoprolol succinate and correlation coefficient were 0.9991 and 0.9997 respectively.Conclusion:The developed method was validated according to the ICH guidelines for precision, accuracy, Limit of detection, Limit of quantitation, specificity and robustness. The method was checked for suitability in determination of Trimetazidine hydrochloride and Metoprolol succinate in their tablet dosage form. The assay result was found to be 99.64 % ± 0.45 and 99.94 % ± 0.53 of percentage label claim for Trimetazidine hydrochloride and Metoprolol succinate respectively.

Role of Extracellular Matrix in Cardiac Cellular Therapies.

The extracellular matrix (ECM) is an essential regulator of homeostasis at the cellular, tissue, and organ level. It is now very well known that ECM dynamic remodeling is indispensable not only for normal growth and development but also recovery from tissue injuries. Indeed, abnormal remodeling of the ECM plays a major role in many pathophysiological processes and contributes to many different pathologies including cardiovascular disorders. Recently, cellular therapies have emerged as a potential therapeutic strategy for restoration of lost cardiomyocytes or their rejuvenation after cardiac damage and injuries. Harnessing the biological properties of ECM could be a viable strategy to enhance the therapeutic effects of cellular therapies by improving the engraftment, integration, survival, and functional adaptation of newly transplanted cells in many different platforms. Conversely, transplanted cells could restore the functionality and original composition of damaged ECM by secreting and depositing new ECM or stimulating normal ECM production by cardiac tissue native cells. Although the ultimate role of cell therapy in treatment of cardiac disorders is still a matter of great debate, the potential utility of ECM in improving the therapeutic effect of transplanted cells and vice versa the potential role of cell therapy as a means to restore the structure and functionality of damaged ECM should be carefully considered in implementation of future clinical cardiovascular cell therapy trials.

Preparation and physicochemical characterization of ingredients of Indian traditional medicine, Mahamrutyunjaya Rasa

BackgroundMahamrutyunjaya rasa is an ayurvedic formulation used in the treatment of cardiac disorders. It contains the purified roots of Visa (Aconitum ferox), Brihati (Solanum indicum), fruits of Pippali Kana (Piper longum), Marica (Piper nigrum), Gandhaka (Sulfur), Hingula (Cinnabar) and Tankana (Sodium metaborate) as per Bhaishajya Ratnavali. The purification (shodhana) process changes the physiochemical properties of the raw materials which need to be studied and understood. ObjectiveThe present work aims to perform a comprehensive physicochemical characterization of raw materials, intermediates and the final product obtained during purification, using modern analytical techniques. Materials and methodsThe standard methods as per traditional text were followed and the physicochemical changes were also investigated by collecting samples at different steps of purification. The samples were analysed using various techniques, viz. Fourier transform infra-red spectroscopic (FTIR), X-ray diffraction (XRD), Differential Scanning Calorimeter (DSC) and High Performance thin Layer chromatography (HPTLC). ResultsThe FTIR and HPTLC analysis of the alkaloidal extracts of Visa showed loss of an ester group with shift in the peaks from 1720 cm−1 (CO stretching of esters) to 1676 cm−1 (CO stretching of Ketone) which signifies the conversion of alkaloid Aconitine (LD50 – 0.08 mg/kg) to Benzoylaconine (LD50 – 24 mg/kg) improving its safety. The analysis of gandhaka by XRD and DSC showed that purification brought about transformation of orthorhombic sulphur into monoclinic sulphur and it reverted back to original form with higher purity. The treatments given to gandhaka and hingula with organic compounds made them homologous to the body tissues. Analysis of purified tankana showed that the processing led to loss of water and slight change in the crystal structure with the shift in the endothermic peak from 110.6 °C to 104.2 °C. ConclusionThus, the present study provides a scientific backing to the methodologies used by Ayurvedic practitioners. The study also provides physicochemical fingerprints for the standardization as well as characterization of raw materials and forms a technical platform for manufacturers to develop quality control standards.

Creation of Nanorobots: Both State-of-the-Science and State-of-the-Art

Over the last decade, remarkable achievements in nanofabrication technology has led to the development of hybrid intelligent systems including the nanomechanical devices powered by the chemical energy sources or biomolecular motors. In this context, nanorobotics has emerged as a highly-advanced technology for designing the fully functional smart devices or robots at nano scale. Development of these highly-controlled and functional nanostructures for sensing, information processing, signaling, and actuation may provide remarkable breakthroughs in medicine such as the improved imaging or targeted therapeutic interventions. Besides the detection and destroying the toxic materials and ecosystem restoration, the stimuli-responsive nanorobots may be used for the diagnosis or treatment of cardiac disorders, traumatic injuries, diabetes, and bacterial or viral infections. These molecular tools with nanoscale resolution facilitates early diagnosis in cancer and precise localization of anticancer agents leading to the minimal side effects. Nanorobots may easily traverse the human body and repair the cells or assist an improper functioning organ. These tiny devices integrated with wireless locomotion, external or internal power supply, artificial intelligence, and smart sensors may also be used for targeted delivery of genes or drugs into the single cells or tissues, tele-operation, or patient monitoring. Indeed, development of the medical nanorobots with a wide range of capabilities is a proof of concept and art in modern science and a breakthrough in nanotechnology which has been highlighted in the present manuscript.

A Comparison Between MRIT2 and NT-ProBNP in Early Detection of Heart Diseases in Thalassemia Major Patients: A Cross-Sectional Study.

One of the most common causes of mortality in major thalassemia is cardiac complications. Despite existence of several methods for diagnosis of cardiac complications in thalassemia, this sequel persists as a major problem in these patients. The aim of this study is to compare the level of serum NT-ProBNP and cardiac MRI T2* in early detection and treatment of cardiac disorders in beta thalassemia major patients. 35 major thalassemic patients on regular transfusion were selected in our center from 2013 to 2014. All of the patients were at least 8years old. NT-ProBNP and MRIT2* analyses were carried out for these patients, and consequently the findings were compared together and analyzed. There is a strong correlation between NT-ProBNP and MRIT2* (p value<0.001) in early detection of cardiac disorders. NT-ProBNP is an important marker for diagnosis of cardiac complications before emergence of heart failure in thalassemic patients. Given the findings of this study, it is recommended that this marker be used on a regular basis for thalassemic patients on regular transfusion.

Cardiac progenitor cells application in cardiovascular disease.

Stem cells (SCs) have special potency to differentiate into different types of cells, especially cardiomyocytes. In order to demonstrate the therapeutic applications of these cells, various investigations are recently being developed. Cardiac progenitor cells are endogenous cardiac SCs that found to express tyrosine kinase receptors, c-Kit and other stemness features in adult heart, contributing to the regeneration of cardiac tissue after injury. This lineage is able to efficiently trans-differentiate into different cell types such as cardiomyocytes, endothelial cells, and smooth muscle cells. Noticeably, several cardiac progenitor cells have been identified until yet. The therapeutic applications of cardiac SCs have been studied previously, which could introduce a novel therapeutic approach in the treatment of cardiac disorders. The current review enlightens the potency of cardiac progenitor cells features and differentiation capacity, with current applications in cardiovascular field.

CARDIAC DISORDER IN HEMODIALYSIS: BENEFITS OF CHINESE HERBS

Background:A major cause of mortality in hemodialysis patients is cardiac disease. Most complementary and alternative therapies, including Chinese herbal medicine, have been useful in the treatment of cardiac disorders.Materials and Methods:A 46 year old Asian woman with chronic renal failure was admitted to the clinic for hemodialysis. In the course of the fifth session of standard dialysis, she developed shock followed by a ventricular tachycardia which rapidly degenerated into cardiac arrest, from which she was resuscitated through cardio-pulmonary resuscitation. The following therapeutic strategies were applied: low discharge oxygen inhalation; stricter water and salt restriction; dialysate temperature set at 36.0 °C; rhEPO 3000u, per week, low molecular weight iron dextran, 200mg/day, intravenously for five days; the patient received Chinese herbal concoction orally.Results:The patient obtained efficient standard dialysis without any cardiac syndrome.Conclusion:Chinese herbs are useful in the management of cardiac disorders in hemodialysis. Chinese herbs may provide more benefits by adjusting dialysis strategies.

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiac Disorders

To evaluate the literature about the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of cardiac disorders, specifically myocardial infarction (MI) and heart failure (HF). Searches were conducted in MEDLINE (1946-May 2016) and Excerpta Medica (1980-May 2016) using EMBASE with the search terms glucagon-like peptide 1, exenatide, albiglutide, liraglutide, dulaglutide, myocardial infarction, heart failure, and cardiovascular The references of relevant articles were reviewed to identify additional citations. Clinical trials were limited to the English language and human trials. In all, 18 trials explored the use of GLP-1 RAs in the treatment of cardiac disorders in patients with and without diabetes mellitus. Of the 18 trials reviewed, 11 trials studied the impact of GLP-1 RAs in MI. All showed a significant beneficial effect on various cardiac parameters. Favorable outcome improvements included myocardial blood flow, left ventricular (LV) function, and MI size. Seven trials reviewed the use of GLP-1 RAs in the treatment of HF. Three trials showed significant improvements in LV ejection fraction, cardiac index, and peak oxygen consumption. Limited data suggest that GLP-1 RAs may be effective for the treatment of cardiac disorders in patients with and without diabetes mellitus. These studies suggest that GLP-1 RAs may have potential pleiotropic beneficial effects in patients with cardiovascular disease beyond their role in managing diabetes. These medications may be cardioprotective after a MI but are less promising in HF.

Noninvasive low-frequency electromagnetic stimulation of the left stellate ganglion reduces myocardial infarction-induced ventricular arrhythmia.

Noninvasive magnetic stimulation has been widely used in autonomic disorders in the past few decades, but few studies has been done in cardiac diseases. Recently, studies showed that low-frequency electromagnetic field (LF-EMF) might suppress atrial fibrillation by mediating the cardiac autonomic nervous system. In the present study, the effect of LF-EMF stimulation of left stellate ganglion (LSG) on LSG neural activity and ventricular arrhythmia has been studied in an acute myocardium infarction canine model. It is shown that LF-EMF stimulation leads to a reduction both in the neural activity of LSG and in the incidence of ventricular arrhythmia. The obtained results suggested that inhibition of the LSG neural activity might be the causal of the reduction of ventricular arrhythmia since previous studies have shown that LSG hyperactivity may facilitate the incidence of ventricular arrhythmia. LF-EMF stimulation might be a novel noninvasive substitute for the existing implant device-based electrical stimulation or sympathectomy in the treatment of cardiac disorders.

Type of treatment of cardiac disorders – quality of life and heart-focused anxiety: The mediating role of illness perceptions

The aim of the present research was to investigate the impact of illness perceptions on quality of life and heart-focused anxiety, in patients with cardiovascular disease (N = 106) admitted in the hospital, undergoing medication or who had undergone surgery. The influence of the type of treatment on the heart-focused anxiety and on the quality of life was mediated by illness perceptions. Consequently, patients who have undergone cardiac surgery have a better quality of life and lower levels of heart-focused anxiety than those relying only on medication to treat their illness.

Modeling Inherited Cardiac Disorders

Advances in the understanding and treatment of cardiac disorders have been thwarted by the inability to study beating human cardiac cells in vitro. Induced pluripotent stem cells (iPSCs) bypass this hurdle by enabling the creation of patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). These cells provide a unique platform to study cardiac diseases in vitro, especially hereditary cardiac conditions. To date, iPSC-CMs have been used to successfully model arrhythmic disorders, showing excellent recapitulation of cardiac channel function and electrophysiologic features of long QT syndrome types 1, 2, 3, and 8, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Similarly, iPSC-CM models of dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) have shown robust correlation of predicted morphologic, contractile, and electrical phenotypes. In addition, iPSC-CMs have shown some features of the respective phenotypes for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), LEOPARD syndrome, Pompe's disease, and Friedriech's ataxia. In this review, we examine the progress of utilizing iPSC-CMs as a model for cardiac conditions and analyze the potential for the platform in furthering the biology and treatment of cardiac disorders.

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FUSION OF TISSUE DOPPLER AND SPECKLE TRACKING IN ECHOCARDIOGRAPHY IMAGES: COMPARISON WITH SPECKLE TRACKING ECHOCARDIOGRAPHY

Quantitative analysis of strain in cardiac imaging is crucial in treatment of cardiac disorders. Thus far, cardiac motion detection is based on tissue Doppler imaging (TDI) or speckle tracking echocardiography (STE). These techniques are based on two independent methods; Doppler effect and image

HCN channels in the heart: lessons from mouse mutants

Hyperpolarization-activated cation channels generate the I(f) current in the heart. In the sino-atrial node (SAN), I(f) is thought to play an essential role in setting the heart rate and mediating its autonomic control. This review focuses on the role of I(f) in pacemaking and non-pacemaking cardiomyocytes and the resulting therapeutic implications. HCN4 represents the principal isoform underlying sino-atrial I(f) , but other isoforms may also be of importance. To examine the functional role of cardiac channels, several mouse mutants, most of them targeting HCN4, have been generated by different groups. Unexpectedly, these lines display greatly different and as yet unexplained phenotypes. We provide an overview about these HCN mutants and suggest an interpretation of the functional significance of I(f) in the SAN in light of these studies. HCN channels are also present in ventricular myocytes, and an up-regulation of I(f) in the hypertrophic and failing heart may contribute to arrhythmogenesis. Inhibition of I(f) by HCN channel blockers is a novel approach in the treatment of cardiac disorders, and ivabradine is approved for treatment of stable angina pectoris. Remarkably, a recent clinical trial assessing this substance in heart failure showed a significantly improved outcome. The mechanism underlying this beneficial effect is not yet clear and might lie beyond heart rate slowing. Thus, the growing knowledge about cardiac HCN channels will undoubtedly promote the development of the promising class of HCN channel blockers.

Transcriptomic Biomarkers for the Accurate Diagnosis of Myocarditis

Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures. Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy. Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.

Knock Down the Disease: Recent Developments in RNA Interference for Treatment of Cardiac Disorders

Genetic and acquired cardiac diseases are potential clinical targets for RNA interfering (RNAi) approaches, which are currently intensely being investigated. This review will give an update on ongoing RNAi treatment of cardiac diseases. Furthermore, small interfering RNA (siRNA) delivery systems, with special focus on cardiomyocyte uptake of siRNA, are discussed.