Detection and categorization of severe cardiac disorders based solely on pulse interval measurements

Cardiac disorders are common conditions associated with a high mortality rate. Due to their potential for causing serious symptoms, it is desirable to constantly monitor cardiac status using an accessible device such as a smartwatch. While electrocardiograms (ECGs) can make the detailed diagnosis of cardiac disorders, the examination is typically performed only once a year for each individual during health checkups, and it requires expert medical practitioners to make comprehensive judgments. Here we describe a newly developed automated system for alerting individuals about cardiac disorders solely based on pulse interval measurements. For this purpose, we examined two metrics of heart rate variability (HRV) and analyzed 1-day ECG recordings of more than 1,000 subjects in total. We found that a newly introduced metric of local variation was more efficient than conventional HRV metrics for detecting premature contraction, and furthermore, that a suitable combination of the old and new metrics resulted in much superior detectability particularly for atrial fibrillation, which requires more attention. Even with a 1-minute recording of pulse intervals, our new detection system had a diagnostic performance even better than that of the conventional analysis method applied to a 1-day recording.

Survey on Prevalence of Vegadharana as a Risk Factor for Cardiac Disorders- An Observational Pilot Study

The present era, which is a reflection of changing major driving forces such as social, economic and cultural due to globalization, urbanization and population ageing. By this change, there is raise in the prevalence of certain non-communicable diseases. Cardiac disorders are among such which stands first in increasing mortality rate about 31% globally. Now a day, the prevalence rate is increasing due to behavioral risk factors like tobacco use, unhealthy diet, obesity, physical inactivity, alcohol and smoking. People are also at higher risk of these disorders with the presence of high risk of one or more already established disease conditions like Hyperlipidemia, Hypertension, Diabetes mellitus etc. Indians are being affected by high rates of these major risk factors which are striking for cardiac disorders at an earlier age almost 33% earlier than other demographical regions. Considering all these many organizations like MRFIT, American Heart association, National Lipid organization etc. are conducting various trials since four decades to establish the appropriate relation with risk factors to plan the better lines of management. Ayurveda explains about the concept of Dharaneeya and Adharaneeya vegas, where in Acharyas emphasize that many of the systemic diseases are caused by the forceful suppression of natural urges. Among 13 Dharaneeya vegas 9 are found to be the risk factors in causing various cardiac disorders. With this regard to explore and to assess the prevalence of Vegadharana as risk factor for cardiac disorders, an attempt has made as a pilot survey study on 40 cardiac patients. Aim: To understand the Prevalence and epidemiology of Vegadharana in Cardiac disorders. To observe the Co-relation between Vegadharana and Cardiac disorders. Methodology: It is a Pilot observational study done by using a survey strategy. The questionnaire method in an electronic format was used to collect the data. Descriptive statistics and Co-relation Co-efficient was used to analyze the data obtained. Result: In this Pilot study, the sum of the prevalence of Vegadharana was observed it was found that the frequency of Vegadharana was more in cardiac individuals, especially the category of few times and sometimes with n value=76 and 64 respectively. Conclusion: With the above data, it can be concluded that; Vegadharana has an impact on the expectancy of Cardiac disorders. The data also revealed the co-relation of Vegadharana in permutation which are signifying as higher risk factors in causing cardiac disorders.

Mettl14 Regulates Cardiac Ishemia/Reperfusion Injury

N6-methyladenosine (m6A) methylation in RNA is a dynamic and reversible modification regulated by methyltransferases and demethylases, which has been reported to participate in many pathological processes of various diseases, including cardiac disorders. This study was designed to investigate an m6A writer Mettl14 on cardiac ischemia–reperfusion (I/R) injury and uncover the underlying mechanism. The m6A and Mettl14 protein levels were increased in I/R hearts and neonatal mouse cardiomyocytes upon oxidative stress. Mettl14 knockout (Mettl14+/−) mice showed pronounced increases in cardiac infarct size and LDH release and aggravation in cardiac dysfunction post-I/R. Conversely, adenovirus-mediated overexpression of Mettl14 markedly reduced infarct size and apoptosis and improved cardiac function during I/R injury. Silencing of Mettl14 alone significantly caused a decrease in cell viability and an increase in LDH release and further exacerbated these effects in the presence of H2O2, while overexpression of Mettl14 ameliorated cardiomyocyte injury in vitro. Mettl14 resulted in enhanced levels of Wnt1 m6A modification and Wnt1 protein but not its transcript level. Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and β-catenin proteins, whereas Mettl14+/− hearts exhibited the opposite results. Knockdown of Wnt1 abrogated Mettl14-mediated upregulation of β-catenin and protection against injury upon H2O2. Our study demonstrates that Mettl14 attenuates cardiac I/R injury by activating Wnt/β-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.

COVID- 19 Infections with and without Co-morbidities and Clinical Outcome

Aim: To evaluate the clinical outcomes and severity of disease in COVID-19 patients presenting with and without comorbidities. Study Design: Cross-sectional study. Place and Duration: ICUs, wards of Jinnah Postgraduate Medical Center Karachi from March, to June 2021. Methodology: The enrolled patients diagnosed with COVID-19 ie according to the provisional directions given by WHO, were assessed for clinical outcomes. Comorbidities were determined based on patients self-report on admission. Results: Total 200 COVID patients were enrolled in the study, out of them 179 were with comorbidities like type 2 Diabetes mellitus, hypertension, cardiac disorders and asthma, while 21 COVID patients were with no co morbidity. In present study (n=200), 55.5% were belonging to the age group more than fifty five years old, there were 50.5% males and 29.5% patients came in the month of June 2021. There were 84% hypertensive, 54% were diabetic, 10% were Ischemic Heart Disease and 5% were Asthmatic patients. Clinical outcomes, i.e., pneumothorax, pulmonary embolism, Myocardial Infarction, septic shock, heart failure, Disseminated Intravascular Coagulation was compared regarding associated co-morbidities at the time of admission, p-value was <0.01 and x2=20.15 . Conclusion: COVID patients with comorbidities are more at risk of developing worst clinical outcomes.

Quantification of Left Ventricular Mass Using Two-Dimensional Transthoracic Echocardiography - A Novel Method with High Accuracy and Reproducibility

Purpose Increased left ventricular mass (LVM) is a strong independent predictor for adverse cardiovascular events, but conventional echocardiographic methods used to assess and monitor individuals are limited by poor reproducibility and accuracy. We aimed to develop an echocardiographic method for LVM-quantification that is simple, reproducible and accurate. Methods The novel method adds the mean wall thickness to the left ventricular end-diastolic volume acquired using the biplane model of discs. The mean wall thickness is acquired from the parasternal short axis view. Cardiac assessment was performed using echocardiography followed immediately by cardiac magnetic resonance in 85 subjects with different left ventricular geometries, ranging from patients with various cardiac disorders (n=41) to individuals without known cardiac disorders (n=44). We compared the novel two-dimensional (2D) method to various conventional one-dimensional (1D) and 2D methods as well as three-dimensional (3D) echocardiography. Results The novel method had better reproducibility in intra-examiner (coefficients of variation (CV) 9% vs. 11-14%) and inter-examiner analysis (CV 9% vs. 10-20%) than the other methods. Accuracy of the novel method was similar to 3D (mean difference±95% limits of agreement, CV): Novel: 2±50g,15% vs. 3D: 2±51g, 16%; and better than the 1D-method by Devereux (7±76g, 23%). Conclusion The novel 2D-based method for LVM-quantification had better reproducibility than the other echocardiographic methods. Accuracy was similar to 3D and better than conventional methods. As endocardial tracings using the biplane model forms part of the standard echocardiographic protocol, the novel method can easily be integrated into any echocardiographic software, without substantially increasing analysis time.

Detection of Cardiac Tissues using K-means Analysis Methods in Nuclear Medicine Images

BACKGROUND: Nuclear cardiology uses to diagnose the cardiac disorders such as ischemic and inflammation disorders. In cardiac scintigraphy, unraveling closely adjacent tissues in the image are challenging issue. AIM: The aim of the study is to detect of cardiac tissues using K-means analysis methods in nuclear medicine images. This study also aimed to reduce the existence of fleck noise that disturbs the contrast and make its analysis more difficult. METHODS: Thus, digital image processing uses to increase the detection rate of myocardium easily using its color-based algorithms. In this study, color-based K-means was used. The scintographs were converted into color space presentation. Then, each pixel in the image was segmented using color analysis algorithms. RESULTS: The segmented scintograph was displayed in distinct fresh image. The proposed technique defines the myocardial tissues and borders precisely. Both exactness rate and recall reckoning were calculated. The results were 97.3 + 8.46 (p > 0.05). CONCLUSION: The proposed technique offered recognition of the heart tissue with high exactness amount.

Gating of RYR2 channels from the arrhythmic RYR2-P2328S mouse heart and some unexpected actions of flecainide

The P2328S mutation in mice is associated with arrhythmia and spontaneous diastolic calcium release in atrial and ventricular myocytes and there is a corresponding leftward shift in the Ca2+-activation curve for mutant RYR2 channels from homozygous mouse hearts (Salvage et al. 2019. J Cell Sci. https://doi.org/10.1242/jcs.229039). P2328 is located in helical domain 1 (HD1) of RYR2. Local structural changes likely result when structurally active proline residues are replaced by structurally inert serine residues. We speculate that local structural changes in HD1 lead to sequential intradomain and interdomain stearic changes through the protein to the distant channel gate, which favor the open pore conformation. The drug flecainide prevents arrhythmia in humans and mouse models of CPVT by blocking NaV1.5 and RYR2 channels. Conventionally, flecainide blocks RYR2 channels in a voltage-dependent manner. We did not observe voltage-dependent pore block. This was possibly because, in contrast to previous studies, the only channel modulators that we used to produce end-diastolic control channel activity were 1 µM cytoplasmic Ca2+ and 1 mM luminal Ca2+. We observed previously unreported, voltage-independent increases in WT and P2328S channel activity at low flecainide concentrations, followed by a decline in activity at higher concentrations. The increase in activity dominated the effect of flecainide on P2328S channels. These effects suggested high-affinity flecainide binding to an activation site and lower-affinity binding to an inhibition site, both distant from the channel pore (Salvage et al. 2021. Cells. https://doi.org/10.3390/cells10082101). Unlike channel block by flecainide, the drug under our conditions stabilized intrinsic sub-conductance activity at +40 mV and −40 mV. Since flecainide effectively reduces CPVT arrythmia clinically and in animal models, we conclude that voltage-independent inhibition and voltage-dependent channel block prevail under cellular conditions. However, channel activation is important to note as it may be unmasked in other circumstances such as acquired cardiac disorders, mutations, or additional drug applications.

Microbial Fibrinolytic Enzymes as Anti-Thrombotics: Production, Characterisation and Prodigious Biopharmaceutical Applications

Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the dissolution of fibrin clots and hence ameliorate thrombosis. Microbial fibrinolytic enzymes have attracted much more attention in the management of cardiovascular disorders than typical anti-thrombotic strategies because of the undesirable after-effects and high expense of the latter. Fibrinolytic enzymes such as plasminogen activators and plasmin-like proteins hydrolyse thrombi with high efficacy with no significant after-effects and can be cost effectively produced on a large scale with a short generation time. However, the hunt for novel fibrinolytic enzymes necessitates complex purification stages, physiochemical and structural-functional attributes, which provide an insight into their mechanism of action. Besides, strain improvement and molecular technologies such as cloning, overexpression and the construction of genetically modified strains for the enhanced production of fibrinolytic enzymes significantly improve their thrombolytic potential. In addition, the unconventional applicability of some fibrinolytic enzymes paves their way for protein hydrolysis in addition to fibrin/thrombi, blood pressure regulation, anti-microbials, detergent additives for blood stain removal, preventing dental caries, anti-inflammatory and mucolytic expectorant agents. Therefore, this review article encompasses the production, biochemical/structure-function properties, thrombolytic potential and other surplus applications of microbial fibrinolytic enzymes.