Major Cardiac Disorders Research Articles

Patient-centred newer testing methods for major cardiac disorders

Patient-centred newer testing methods for major cardiac disorders

Modified mRNA-Mediated CCN5 Gene Transfer Ameliorates Cardiac Dysfunction and Fibrosis without Adverse Structural Remodeling.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure.

Review on Characteristics and Analytical Methods of Remogliflozin Etabonate: An Update.

Hyperglycemia and its associated disorders like Diabetes mellitus are engulfing the world's population at a faster pace. New-age medications like the SGLT 2 inhibitors have found their place in the run to combat DM. Drugs with these properties have proven to be effective in treating hyperglycemia, obesity, and major cardiac disorders. The interesting fact about these drugs is that they act independently of insulin levels in the patient's body. The fact that they even bypass the side effects shown by currently used anti-diabetic medications has attracted the world's hope to neutralize diabetes mellitus. The invention of Remogliflozin Etabonate (RGE), an SGLT 2 inhibitor, has therefore added a silver lining to the gliflozin-family of drugs in the fight against DM. This is due to its least side effects as well as its effective mechanisms to treat hyperglycemia. It can be administered not only as a single entity but also can be co-administered in combination with other anti-hyperglycemic agents. RGE is already sold in the Indian market as REMO-ZEN, by Glenmark Pharmaceuticals. It has been studied thoroughly for its pharmacokinetic and pharmacodynamic profile. It is a benzylpyrazole glucoside. Various analytical methods have been formulated for its detection, quantification, and routine quality control activities. RGE can be studied with the help of UV-visible spectrophotometry, High-Performance Liquid Chromatography (HPLC) and Hyphenated techniques like Liquid Chromatography- Mass Spectroscopy (LC-MS/MS). This review briefs about the overall chemical, pharmacological, pharmacokinetic and pharmacodynamics properties of RGE. It mainly discusses various analytical techniques used for determining and estimating RGE.

Outcome of fetuses with soft markers: results of 3016 cases in Ahvaz city.

Background: Although soft markers may be seen as normal variants, they are important due to their association with chromosomal and congenital abnormalities. Methods: This cross-sectional descriptive-analytical study was done on 3016 women who referred for perinatal care. Fetuses with any of soft markers including thickened nuchal fold (TNF), mild pyelectasis (MP), choroid plexus cyst (CPC), single umbilical artery (SUA), mega cisterna magna (MCM) and mild ventriculomegaly (MVM) were followed during pregnancy and birth. Data analysis was carried out using SPSS for Windows (version 22). Data were analyzed using chi-square and T-test. A p-value <0.050 was considered statistically significant. Results: 285 (9.4%) fetuses with soft markers Including 148 (4.9%) fetuses with CPC, 118 (3.9%) fetuses with MP, 2 (0.1%,) fetuses with isolated TNF, 8 (0.3%) fetuses with isolated MVM, 4 (0.13%) fetuses with SUA, 4 (0.13%) fetuses with MCM were identified, and one fetus had TNF and MVM simultaneously. In cases with CPC, no abortion or major structural abnormalities were observed and all 148 neonates had normal phenotypes at birth. Among 118 cases with MP, one case had a major cardiac disorder, and 2 cases of abortions (1.7%) were reported (p=0.481). 83 cases (70.3%) were male and 35 cases (29.7%) were female (p=0.021) and all neonates had a normal phenotype. Both pregnancies with isolated TNF resulted in abortion. Of the 8 cases with isolated MVM, two cases had major structural abnormalities. 2 cases of abortion were reported and all infants had a normal phenotype. In one case, that fetus had TNF and MVM simultaneously. Amniocentesis showed no aneuploidy. No major structural abnormalities were observed in fetuses with SUA. One case of abortion was reported. Among the three births, two pre-term births were reported, and all three infants had normal phenotype. In four cases with MCM, no major structural abnormality was observed and all four neonates had normal phenotype. Conclusion: In cases without association with other structural abnormality, mothers who have fetuses with CPC or MP should be reassured that the pregnancy outcomes are generally favorable.

Trimetazidine in cardiovascular medicine

Abnormalities of myocardial energy metabolism appear as a common background of the two major cardiac disorders: ischemic heart disease (IHD) and heart failure (HF). Myocardial ischemia has been recently conceived as a multifaceted syndrome that can be precipitated by a number of mechanisms including metabolic abnormalities. HF is a progressive disorder characterised by a complex interaction of haemodynamic, neurohormonal and metabolic disturbances. HF may further promote metabolic changes, generating a vicious cycle. Thus, targeting cardiac metabolism in IHD patients may prevent the deterioration of left ventricular function, stopping the progression to HF. For these reasons, several studies have explored the potential benefits of trimetazidine (TMZ), an inhibitor of free fatty acids oxidation that shifts cardiac and muscle metabolism to glucose utilization.Because of its mechanism of action, TMZ has been found to provide a cardioprotective effect in patients with angina, diabetes mellitus, and left ventricular (LV) dysfunction, and those undergoing revascularization procedures, without relevant side effects. In addition, the lack of interference with heart rate, arterial pressure, and most of frequent comorbidities, makes TMZ an attractive option for patients and clinicians as well. The impact of TMZ on long term mortality and morbidity in ischemic syndromes and in heart failure need to be conclusively confirmed in properly designed RCT.

Risk factors for sudden cardiac death to determine high risk patients in specific patient populations that may benefit from a wearable defibrillator.

BACKGROUNDThere is a high risk for sudden cardiac death (SCD) in certain patient groups that would not meet criteria for implantable cardioverter defibrillator (ICD) therapy. In conditions such as hypertrophic cardiomyopathy (HCM) there are clear risk scores that help define patients who are high risk for SCD and would benefit from ICD therapy. There are however many areas of uncertainty such as certain patients post myocardial infarction (MI). These patients are high risk for SCD but there is no clear tool for risk stratifying such patients.AIMTo assess risk factors for sudden cardiac death in major cardiac disorders and to help select patients who might benefit from Wearable cardiac defibrillators (WCD).METHODSA literature search was performed looking for risk factors for SCD in patients post-MI, patients with left ventricular systolic dysfunction (LVSD), HCM, long QT syndrome (LQTS). There were 41 studies included and risk factors and the relative risks for SCD were compiled in table form.RESULTSWe extracted data on relative risk for SCD of specific variables such as age, gender, ejection fraction. The greatest risk factors for SCD in post MI patients was the presence of diabetes [Hazard ratio (HR) 1.90-3.80], in patient with LVSD was ventricular tachycardia (Relative risk 3.50), in LQTS was a prolonged QTc (HR 36.53) and in patients with HCM was LVH greater than 20 mm (HR 3.10). A proportion of patients currently not suitable for ICD might benefit from a WCDCONCLUSIONThere is a very high risk of SCD post MI, in patients with LVSD, HCM and LQTS even in those who do not meet criteria for ICD implantation. These patients may be candidates for a WCD. The development of more sensitive risk calculators to predict SCD is necessary in these patients to help guide treatment.

Getting to the "Heart" of Cardiac Disease by Decreasing Mitochondrial Iron.

Iron chelation rather than supplementation would be beneficial to patients with heart diseases. More effort should be devoted to the development of iron chelators that could target mitochondrial iron. Iron is an essential trace mineral for normal mammalian physiology. It is incorporated into iron/sulfur (Fe/S) clusters that serve as important cofactors for many enzymes, including the mitochondrial respiratory chain, and it gives blood and muscle their signature red color through its presence in heme.1 Because of its involvement in many important cellular processes, dysregulation of iron often causes disease. There are 2 broad categories of diseases associated with iron dysregulation—iron overload and iron deficiency. Each category can be further subdivided based on whether the changes in iron occur at the cellular or at the systemic level. Iron is critical for developmental processes, and studies have linked severe systemic iron deficiency to impaired brain development in children.2 However, most of these studies were conducted in developing countries where iron deficiency tends to be more severe. In developed countries, the major disorder associated with iron deficiency is anemia. Although systemic iron deficiency and anemia may have been used interchangeably, these 2 terms refer to different conditions. Systemic iron deficiency refers to low amounts of iron in circulation because of limited iron absorption or excess iron loss. Anemia is defined as low hemoglobin content within red blood cells and can be caused by low systemic iron, mutations in hemoglobin genes, vitamin B12 deficiency, or underlying chronic diseases. Limited oxygen-carrying capacity secondary to anemia can cause fatigue; however, it generally does not cause mortality or major damage to vital organs. Except for high-output heart failure (HF) associated with severe anemia, iron deficiency and anemia are not associated with any other major cardiac disorders. Cellular iron deficiency is a rare phenomenon, and except …

Relationship between isolated mild tricuspid valve regurgitation in second-trimester fetuses and postnatal congenital cardiac disorders.

In most cases, the clinical importance of fetal isolated mild tricuspid valve regurgitation is not known. This study evaluated the relationship between fetal isolated mild tricuspid regurgitation in the general obstetric population and postnatal congenital cardiac disorders. Detailed fetal echocardiography was done between 18 and 24 weeks' gestation to detect tricuspid regurgitation and to exclude complicated cardiac defects. Routine second-trimester targeted organ scans were also performed to exclude extracardiac defects. Follow-up was done until birth. After birth, the cardiac anatomy of the neonates was examined by echocardiography. The association between fetal isolated mild tricuspid regurgitation and postnatal congenital cardiac disorders was assessed by logistic regression analysis. No major cardiac disorders were found postnatally. Some minor disorders were found, including a patent foramen ovale, atrial septal defects, a patent ductus arteriosus, and small ventricular septal defects. Fetuses with isolated mild tricuspid regurgitation had a significantly higher likelihood of having ventricular septal defects (odds ratio, 5.80; P = .027) or a patent foramen ovale with atrial septal defects and a patent ductus arteriosus (odds ratio, 11.61; P = .007). There was no significant association between tricuspid regurgitation and an isolated patent foramen ovale or a patent foramen ovale with atrial septal defects in neonates. Fetuses with isolated mild tricuspid regurgitation in the second trimester did not have a higher incidence of major cardiac disorders after birth. The presence of isolated mild tricuspid regurgitation may be an indication of minor postnatal congenital cardiac disorders.

Age Disparities in Heart Failure Research

Age Disparities in Heart Failure Research

Rewiring the Heart: Stem Cell Therapy to Restore Normal Cardiac Excitability and Conduction

The regenerative capacity of the mammalian heart is insufficient to recover from myocardial infarction. Stem cells are currently considered as a promising and valuable tool to replace the, often large, loss of contractile tissue. One of the bottlenecks hampering fast clinical application is the large amount of cells required to replace a single damaged region combined with an appropriate strategy to succeed in homogeneous repair. A second class of major cardiac disorders for which stem cell therapy might be fruitful and would require less cells for repair, are chronic rhythm disorders. In this area, most research has been focused on stem-cell based biological pacemakers, but increasing amounts of data on AV nodal repair appear in literature. Both therapies, in principle, could eventually replace current instrumentation with electronic pacemakers. Finally, an emerging field of interest explores transplantation of stem cells expressing specific ion channels aiming at suppression of focal arrhythmias, providing an alternative strategy for surgical and catheter-mediated ablation. Since in this second class of applications the number of transplanted cells required may be relatively low, effective clinical therapy may be within close range. Here, we will review recent achievements in the fields of stem-cell based biological pacemakers, AV nodal repair and biological ablation.

Myocardial ischemia/reperfusion injury in the inducible nitric oxide synthase knockout mice

Inducible nitric oxide synthase (iNOS) plays an important role in the inflammatory process of certain major cardiac disorders including myocardial infarction and allograft rejection. However, the role of iNOS in acute myocardial ischemia has not been well defined. We determined the effects of genetically disruption of the intact iNOS system on cardiac tolerance to ischemia/reperfusion injury. Adult male wild-type(WT) and iNOS knockout (KO) B6,129 mice were subjected to 20 min global ischemia and 30 min reperfusion in a Langendorff isolated perfused heart model (37 ° C, n = 10/each group). Ventricular contractile function, heart rate, coronary flow, and leakage of intracellular enzymes (CK and LDH) were not significantly different between the groups during pre-ischemia as well as reperfusion period ( P > 0.05). Myocardial infarct size was also not significantly different between WT (20.2 ± 2.0% of risk area) and KO mice (23.5 ± 3.8%; Mean ± SEM, P > 0.05). However, the post-ischemic heart rate was significantly preserved in KO as compared to WT ( P < 0.05). We conclude that disruption of iNOS gene does not exacerbate ischemia/ reperfusion injury in the heart.

The Diagnostic Performance of Computer Programs for the Interpretation of Electrocardiograms

Computer programs for the interpretation of electrocardiograms (ECGs) are now widely used. However, a systematic assessment of various computer programs for the interpretation of ECGs has not been performed. We undertook a large international study to compare the performance of nine electrocardiographic computer programs with that of eight cardiologists in interpreting ECGs in 1220 clinically validated cases of various cardiac disorders. ECGs from the following groups were included in the sample: control patients (n = 382); patients with left ventricular hypertrophy (n = 183), right ventricular hypertrophy (n = 55), or biventricular hypertrophy (n = 53); patients with anterior myocardial infarction (n = 170), inferior myocardial infarction (n = 273), or combined myocardial infarction (n = 73); and patients with combined infarction and hypertrophy (n = 31). The interpretations of the computer programs and the cardiologists were compared with the clinical diagnoses made independently of the ECGs, and the computer interpretations were compared with those of the cardiologists. The percentage of ECGs correctly classified by the computer programs (median, 91.3 percent) was lower than that of the cardiologists (median, 96.0 percent; P less than 0.01). The median sensitivity of the computer programs was also significantly lower than that of the cardiologists in diagnosing left ventricular hypertrophy (56.6 percent vs. 63.9 percent, P less than 0.02), right ventricular hypertrophy (31.8 percent vs. 46.6 percent, P less than 0.01), anterior myocardial infarction (77.1 percent vs. 84.9 percent, P less than 0.001), and inferior myocardial infarction (58.8 percent vs. 71.7 percent, P less than 0.0001). The median total accuracy level (the percentage of correct classifications) was 6.6 percent lower for the computer programs (69.7 percent) than for the cardiologists (76.3 percent; P less than 0.001). However, the performance of the best programs nearly matched that of the most accurate cardiologists. Our study shows that some but not all computer programs for the interpretation of ECGs perform almost as well as cardiologists in identifying seven major cardiac disorders.