Novel and deleterious nucleotide variations in the HAND1 gene probably affect miRNA target sites and protein function in pediatric patients with congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent developmental defect and principal cause of infant mortality and affects cardiac and large blood vessel structures in approximately 1% of live births worldwide. To date, numerous studies have related critical genetic dysfunctions to the pathogenesis of CHDs. However, the genetic basis underlying CHD remains largely unknown. In the present study, we investigated the association of nucleotide variations in coding and noncoding regions of the HAND1 gene with the risk of CHD. The HAND1 gene, encoding a helix-loop-helix transcription factor, is particularly relevant for mechanisms underlying CHD since it plays a significant role in heart development. METHODS AND RESULTS: The genomic DNA of 150 unrelated pediatric patients with CHD was screened by PCR-SSCP and direct sequencing. Four novel and heterozygous missense mutations were identified in the first exon, with three causing amino acid substitutions (p.Val149Met, p.Tyr142His, and p.Leu146Met). In-silico analysis also indicated their deleterious impact on protein structure and function. In addition, we identified five novel nucleotide variants in the 3'UTR region (c.*461, c.*342, c.*529, c.*448, c.*593), potentially altering the target sites of miRNAs. These changes include the loss of certain target sites and the acquisition of new ones. CONCLUSIONS: These findings confirm the phenotypic association between CHDs and HAND1 mutations and can pave the way for developing new preventive and therapeutic strategies.

Mitochondrial mutations in protein coding genes of respiratory chain including complexes IV, V, and mt-tRNA genes are associated risk factors for congenital heart disease.

Most studies aiming at unraveling the molecular events associated with cardiac congenital heart disease (CHD) have focused on the effect of mutations occurring in the nuclear genome. In recent years, a significant role has been attributed to mitochondria for correct heart development and maturation of cardiomyocytes. Moreover, numerous heart defects have been associated with nucleotide variations occurring in the mitochondrial genome, affecting mitochondrial functions and cardiac energy metabolism, including genes encoding for subunits of respiratory chain complexes. Therefore, mutations in the mitochondrial genome may be a major cause of heart disease, including CHD, and their identification and characterization can shed light on pathological mechanisms occurring during heart development. Here, we have analyzed mitochondrial genetic variants in previously reported mutational genome hotspots and the flanking regions of mt-ND1, mt-ND2, mt-COXI, mt-COXII, mt-ATPase8, mt-ATPase6, mt-COXIII, and mt-tRNAs (Ile, Gln, Met, Trp, Ala, Asn, Cys, Tyr, Ser, Asp, and Lys) encoding genes by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) in 200 patients with CHD, undergoing cardiac surgery. A total of 23 mitochondrial variations (5 missense mutations, 8 synonymous variations, and 10 nucleotide changes in tRNA encoding genes) were identified and included 16 novel variants. Additionally, we showed that intracellular ATP was significantly reduced (P=0.002) in CHD patients compared with healthy controls, suggesting that the mutations have an impact on mitochondrial energy production. Functional and structural alterations caused by the mitochondrial nucleotide variations in the gene products were studied in-silico and predicted to convey a predisposing risk factor for CHD. Further studies are necessary to better understand the mechanisms by which the alterations identified in the present study contribute to the development of CHD in patients.

Novel Point Mutations in 3'-Untranslated Region of GATA4 Gene Are Associated with Sporadic Non-syndromic Atrial and Ventricular Septal Defects.

OBJECTIVE: Transcription factor GATA4 has significant roles in embryonic heart development. Mutations of GATA4 appear to be responsible for a wide variety of congenital heart defects (CHD). Despite the high prevalence of GATA4 mutations in CHD phenotypes, extensive studies have not been performed. The 3'-untranslated region (3'-UTR) of the GATA4 gene comprises regulatory motifs and microRNA binding sites that are critical for the appropriate gene expression, nuclear transportation, and regulation of translation, and stability of mRNA. This study aimed to evaluate the association between mutations in the 3'-UTR of the GATA4 gene and CHD risk among Iranian patients. METHODS: We analyzed the coding region of exon 6 and the whole 3'-UTR of GATA4 in DNA isolated from 175 blood samples of CHD patients and 115 unrelated healthy individuals. The functional importance of the observed GATA4 mutations was evaluated using a variety of bioinformatics algorithms for assessment of nonsynonymous mutations and those observed in miRNA binding sites of 3'-UTR. RESULTS: Twenty-one point mutations including one missense mutation (c.511A>G: p.Ser377Gly) in exon 6 and 20 nucleotide variations in 3'-UTR of GATA4 gene were identified in 65 of the 175 CHD patients. In our patients, we identified 12 novel sequence alterations and 8 single nucleotide polymorphisms in the 3'-UTR of GATA4. Most of them had statistically significant differences between CHD patients and controls. CONCLUSION: Our results suggest that 3'-UTR variations of the GATA4 gene probably change microRNA binding sites and present an additional molecular risk factor for the susceptibility of CHD.

Relationship of hypomethylation CpG islands in interleukin-6 gene promoter with IL-6 mRNA levels in patients with coronary atherosclerosis.

Introduction: Atherosclerosis is the important cause of most cardiovascular diseases, with high prevalence and mortality. Atherosclerosis is not only a lipid metabolism disorder but also recently is defined as a chronic inflammatory disease. Several studies showed that interleukin-6 (IL-6) is involved in the pathogenesis of atherosclerosis. The aim of the present study is the examination of IL6 mRNA Levels and hypomethylation of IL6 promoter in atherosclerosis patients. Methods: In this assay, a total of 35 cases with atherosclerosis and 30 controls were enrolled. RNA and DNA were isolated from the peripheral blood of all samples. Mean IL6 gene expression was determined by RT-PCR and methylation status at six CpG motifs in IL6 promoter was determined using bisulfite genomic sequencing. Results: Real Time-PCR analysis results showed the mean IL6 RNA level in atherosclerosis patients candidate for CABG (coronary artery bypass grafting) was significantly higher than controls (P value = 0.01). Also, the upstream CpG motifs (-1038 to -952) in IL6 promoter were predominantly unmethylated in patients than in the controls (P value = 0.01). Conclusion: These findings suggest that an increase in IL-6 gene expression and its DNA hypomethylation promoter are associated with atherosclerosis patient's candidate for CABG surgery.

Novel Point Mutations in Mitochondrial MT-CO2 Gene May Be Risk Factors for Coronary Artery Disease.

A wide range of genetic and environmental interactions are involved in the development of coronary artery disease (CAD). Considerable evidence suggests that mitochondrial DNA mutations are associated with heart failure. In this work, we examined the possible mutations in hotspot mitochondrial genes and their association with Iranian patients with coronary artery disease. In this case-control study, nucleotide variations were investigated in 109 patients with coronary atherosclerosis and 105 control subjects with no family history of cardiovascular disease. The molecular analysis of related mitochondrial genes was performed by polymerase chain reaction sequencing. Our results showed 25 nucleotide variations (10 missense mutations, 9 synonymous polymorphisms, and 6 variants in tRNA genes) that for the first time were presented in coronary artery disease. Our results suggest that novel heteroplasmic m.8231 C>A mutation is involved in CAD (p = 0.007). These nucleotide variations suggest the role of mitochondrial mutations as a predisposing factor which in combination with environmental risk factors may affect the pathogenesis of coronary atherosclerosis. So, further investigation is needed for a better understanding of the pathogenesis and predisposing effects of these variations on the disease.

Novel Point Mutations of CITED2 Gene Are Associated with Non-familial Congenital Heart Disease (CHD) in Sporadic Pediatric Patients.

CITED2 is a cardiac transcription factor that plays a critical role in cardiac development. Gene mutations in CITED2 lead to a series of cardiac malformations and congenital heart defects (CHD). Congenital heart disease generally refers to defects in the heart's structure or function and often seen in many forms such as ventricular septal defects (VSDs), atrial septal defects (ASDs), and tetralogy of Fallot (TOF). However, the mechanisms involved in these mutations are poorly understood. The aim of the present study was to evaluate the mutations of the CITED2 gene in pediatric patients with congenital heart defects. We studied the potential impact of sequence variations of the CITED2 gene in a cohort of 150 patients with non-familial CHD and 98 control individuals by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and subsequently direct sequencing. We identified seven novel CITED2 nucleotide changes. Four of these alterations were found in the coding region (c.716insG, c.389A>G, c.450G>C and c.512-538del27) and were only seen in our patients, and not detected in the control group. These mutations are leading to changes in the amino acid sequence in the position of p.Gly236fs, p.Asn125Ser, p.Gln145His, and p.Ser170-Gly178del, respectively. Other variations are located in the 5'UTR region of the gene (c.-43C>T, c.-64C>T and c.-90A>G). CITED2 gene mutations in control subjects were not observed. Our Bioinformatics assay results showed that these novel mutations alter the RNA folding, protein structure, and, therefore, probable effect on the protein function and may play a significant role in the development of congenital heart diseases.

Comparison of Short-Term Results between Patients Undergoing Coronary Artery Bypass Graft with a Stent-Placement History and Patients Undergoing Primary Coronary Artery Surgery.

Background: Percutaneous coronary intervention (PCI) has become the first-choice treatment strategy the world over for patients with chronic coronary artery disorders. This study compared the effects of previous PCI procedures on the short-term postoperative results of coronary artery bypass graft surgery (CABG). Methodsː This cross-sectional analytical study recruited 220 patients who underwent CABG in Afshar Hospital in the Iranian city of Yazd between March 2009 and February 2013. The mean postoperative morbidity and mortality rates, the mean postoperative left ventricular ejection fraction (LVEF), the mean hemorrhage volume, the mean serum urea level, and the mean length of stay in the intensive care unit (ICU) were compared between the PCI and non-PCI groups. Results: Among the 220 participants, 147(66.8%) were male and 73(33.2%) were female. The mean age of the study population was 59.41±10.52 years. There was no significant difference in the risk of mortality between the 2 groups (P=0.369). The mean serum urea level was 21.14±6.52 mg/dL in the PCI group and 14.45±1.08 mg/dL in the non-PCI group (P=0.016). The mean postoperative LVEF was 43.19±8.81% in the PCI group and 45.51±8.15% in the non-PCI group (P=0.044). The mean length of stay in the ICU was 3.34±1.23 days in the PCI group and 2.22±0.56 days in the non-PCI group (P<0.001). The mean hemorrhage volume was 1113.01±428.13 mL in the PCI group and 961.42±228.31 mL in the non-PCI group (P=0.027). Conclusion: Previous PCI procedures did not affect the post-CABG mortality rate; however, some postoperative results were worse in the PCI group than in the non-PCI group, which should be considered before the selection of the revascularization method.

Development of One-Step Tetra-primer ARMS-PCR for Simultaneous Detection of the Angiotensin Converting Enzyme (ACE) I/D and rs4343 Gene Polymorphisms and the Correlation with CAD Patients.

BACKGROUND: The Angiotensin Converting Enzyme (ACE) Insertion/Deletion and rs-4343 gene polymorphisms could be associated with pathogenesis of essential hypertension and cardiovascular disorders and Coronary Artery Disease (CAD). In the present study, a fast and novel approach of multiplex Tetra-Primer Amplification Refractory Mutation System-PCR (T-ARMS-PCR) was developed for simultaneous detection of two SNPs including ACE I/D (rs4340) and 2350A>G (rs4343) of Angiotensin Converting Enzyme (ACE) gene. METHODS: The present research was performed using 148 blood samples taken from patients with CAD and 135 healthy individuals. One set of inner primers (for rs4343) and one set of outer primer pairs were designed for genotyping of Insertion/Deletion and rs4343 polymorphisms in single tube T-ARMS-PCR. RESULTS: Our results manifested that genotypes and alleles frequency of the ACE polymorphisms showed no statistically significant association between CAD patients and the control group. In addition, complete concordance was seen between sensitive Tetra-ARMS-PCR and sequencing method. CONCLUSION: The technique is the first work for simultaneous detection of Insertion/Deletion polymorphism and rs4343 SNPs in ACE gene and the results were entirely according to those from an independent procedure.

Novel Point Mutations in the NKX2.5 Gene in Pediatric Patients with Non-Familial Congenital Heart Disease.

Background and objective: Congenital heart disease (CHD) is the most common birth abnormality in the structure or function of the heart that affects approximately 1% of all newborns. Despite its prevalence and clinical importance, the etiology of CHD remains mainly unknown. Somatic and germline mutations in cardiac specific transcription factor genes have been identified as the factors responsible for various forms of CHD, particularly ventricular septal defects (VSDs), tetralogy of Fallot (TOF), and atrial septal defects (ASDs). p. NKX2.5 is a homeodomain protein that controls many of the physiological processes in cardiac development including specification and proliferation of cardiac precursors. The aim of our study was to evaluate the NKX2.5 gene mutations in sporadic pediatric patients with clinical diagnosis of congenital heart malformations. Materials and methods: In this study, we investigated mutations of the NKX2.5 gene's coding region in 105 Iranian pediatric patients with non-familial CHD by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) and direct sequencing. Results: We observed a total of four mutations, of which, two were novel DNA sequence variants in the coding region of exon 1 (c. 95 A > T and c. 93 A > T) and two others were previously reported as single-nucleotide polymorphisms (SNPs), namely rs72554028 (c. 2357 G > A) and rs3729753 (c. 606 G > C) in exon 2. Further, observed mutations are completely absent in normal healthy individuals (n = 92). Conclusion: These results suggest that NKX2.5 mutations are highly rare in CHD patients. However, in silico analysis proves that c.95 A > T missense mutation in NKX2.5 gene is probably pathogenic and may be contributing to the risk of sporadic CHD in the Iranian population.

Novel and heteroplasmic mutations in mitochondrial tRNA genes in Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is a rare cardiac arrhythmia characterized by sudden death associated with electrocardiogram patterns characterized by incomplete right bundle-branch block and ST-segment elevations in the anterior precordial leads. This syndrome predominantly is seen in younger males with structurally normal hearts. Mitochondrial variants particularly mt-tRNA mutations, are hot spots that lead to cardiological disorders. Previous studies have shown that mutations in mitochondrial tRNA genes play an important causal or modifying role in BrS. The present study aims to evaluate the involvement of mitochondrial tRNA genes in arrhythmogenic BrS. METHODS: In this study, 40 Iranian patients were investigated for the presence of the mutations in 6 mitochondrial tRNA genes (tRNA Ile, Met, Gln, Asn, Ala and Trp) by PCR-SSCP analysis. RESULTS: There were 4 mutations in tRNA genes, that for first time, were found in BrS patients and these mutations were not in controls. Three of them were heteroplasmic and located in tRNAGln (T4377A) and tRNAMet (G4407A and C4456T) which were assessed as pathogenic mutations. A homo-plasmic variant (5580T > C) in tRNATrp gene was located within the junction region between tRNATrp and tRNAAla genes. This mutation may disturb the processing of mt-tRNATrp. CONCLUSIONS: The results of this study suggest that mutations in mitochondrial tRNA genes might lead to deficiencies in translational process of critical proteins of the respiratory chain and potentially lead to BrS in Iranian subjects. (Cardiol J 2018; 25, 1: 113-119).

Simultaneous Genotyping of the rs4762 and rs699 Polymorphisms in Angiotensinogen Gene and Correlation with Iranian CAD Patients with Novel Hexa-primer ARMS-PCR.

BACKGROUND: A significant role of Renin-angiotensin system (RAS) genetic variants in the pathogenesis of essential hypertension and cardiovascular diseases has been proved. This study aimed to develop a new, fast and cheap method for the simultaneous detection of two missense single nucleotide polymorphisms (T207M or rs4762 and M268T orrs699) of angiotensinogen (AGT) in single-step Multiplex Hexa-Primer Amplification Refractory Mutation System - polymerase chain reaction (H-ARMS-PCR). METHODS: In this case-control study, 148 patients with coronary artery disease (CAD) and 135 controls were included. The patients were referred to cardiac centers in Afshar Hospital (Yazd, Iran) from 2012 to 2015. Two sets of inner primer (for each SNP) and one set outer primer pairs were designed for genotyping of rs4762 and rs699 in single tube H-ARMS-PCR. Direct sequencing of all samples was also performed to assess the accuracy of this method. DNA sequencing method validated the results of single tube H-ARMS-PCR. RESULTS: We found full accordance for genotype adscription by sequencing method. The frequency of the AGT T521 and C702 alleles was significantly higher in CAD patients than in the control group (OR: 0.551, 95% CI: 0.359-0.846, P=0.008 and OR: 0.629, 95% CI: 0.422-0.936, P=0.028, respectively). CONCLUSION: This is the first work describing a rapid, low-cost, high-throughput simultaneous detection of rs4762 and rs699 polymorphisms in AGT gene, used in large clinical studies.

Efficacy of Preoperative Color Doppler Sonography of Lower Extremity Veins on Postoperative Outcomes in Candidates of Saphenectomy: A Randomized Clinical Trial.

BACKGROUND: Doppler sonography is a type of sonography used for imaging the blood flow in the vessels and heart. This technique uses ultrasound waves with high frequency. In some patient candidates for venous graft, the identification of the suitable vein is not possible with clinical examination. OBJECTIVE: This study compared the effects of preoperative color Doppler sonography of lower extremity veins on the postoperative outcomes of saphenectomy. METHODS: This randomized clinical trial was conducted on 100 candidates of an off-pump coronary artery bypass graft (CABG) hospitalized in Afshar Hospital in Yazd in 2015. Patients were divided into two groups: 50 patients in the study group and 50 patients in the control group. Patients in the study group underwent color Doppler sonography of lower extremity veins using the Medison 8000 Live device. Patients in the control group were assessed preoperatively by routine venous examination without undergoing color Doppler sonography. The prepping and draping methods and also the preoperative antibiotics were the same for both groups. The patients were assessed for wound infection, edema, hematoma, and DVT 2 days, 1 week, and 1 month after surgery. Data were analyzed by SPSS version 16 using t-test, Chi-square, and Fisher's exact test. RESULTS: The length of incision for saphenectomy was 29.20 ± 3.71 cm in the Doppler group and 28.98 ± 3.72 cm in the non-Doppler group with no significant difference between the two groups (p=0.768). The two groups were not significantly different with respect to age, gender, diabetes, hypertension, hyperlipidemia, smoking, and history of peripheral vessels disease, postoperative infection, postoperative organ edema, postoperative hematoma, and postoperative DVT. CONCLUSION: Preoperative color Doppler sonography of the saphenous vein before saphenectomy has no effect on reducing the postoperative complications, and saphenectomy on the basis of intraoperative examination of the vein course by the surgeon has acceptable consequences. CLINICAL TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (TCTR) (http://www.clinicaltrials.in.th) with the TCTR ID: TCTR20160708001. FUNDING: The authors received no financial support for the research, authorship, and/or publication of this article.

Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients.

BACKGROUND: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. OBJECTIVES: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. PATIENTS AND METHODS: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. CONCLUSIONS: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population.

Experience with percutaneous closure of ductus arteriosus using the Amplatzer duct occluder in 243 consecutive patients and long-term results-A single centre study.

BACKGROUND: Percutaneous closure of patent ductus arteriosus (PDA) with Amplatzer duct occluder (ADO) has become increasingly popular in many cardiovascular centres. This study analysed the long-term results of percutaneous closure of PDA with ADO in a single centre. MATERIALS AND METHODS: Between May 2004 and January 2013, 243 patients with median age of 2.5 years (range = 30 months to 38 years) and median weight of 10 Kg (range 4.5-80.5 Kg) underwent percutaneous closure of PDA using the ADO. The devices were implanted under fluoroscopic guidance. Patients were followed-up for any complications. RESULTS: The mean diameter of narrow part of PDA was 6.4 ± 2.2 mm. The mean diameter of devices was 7.8 ± 2.3 mm. The devices were successfully implanted in 239 (98.3%) cases. At immediate, 1 day, 1, 6, 12 months and late follow-up, the complete occlusion rate was 33% (79 case), 97.1% (236 case), 97.5% (237 case), 98.3% (238 case), 98.3% (238 case) and 98.3% (238 case), respectively. Residual shunt remained in one case at late follow-up. The device embolisation occurred in five patients. The devices were successful retrieved in three patient and second larger devices were inserted. Two other devices were surgically retrieved and PDAs were ligated. Moderate left pulmonary artery stenosis (LPA) in one child and mild LPA stenosis in one infant were detected. Mild aortic obstruction occurred in one infant. CONCLUSIONS: Long-term follow-up of patients indicate that percutaneous closure of PDA using ADO is a safe and effective procedure. However, some complications, including device embolisation, left pulmonary stenosis and aortic obstruction may be observed in some cases.

Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB). The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%), candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 µg/kg) intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 µg/kg/min). Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05). The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031). There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

Apolipoprotein e gene polymorphism in Iranian coronary atherosclerosis patients candidate for coronary artery bypass graft.

UNLABELLED: Objective(s) : Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary artery disease (CAD) risk. The aim of this study was to study the association of the Apolipoprotein E genotypes with coronary artery disease in the Iranian population. MATERIALS AND METHODS: The Apolipoprotein E genotype in DNA samples extracted from 66 CAD+ patients and 61 control subjects by restricting enzyme digestion of amplified exon 4 APOE gene was determined. Results : The ε3 allele was found at similar frequency in control subjects (88.5%) and atherosclerosis patients (83.3%) (P=0.314). Our results showed that the frequency of the ɛ3/ɛ3 and ε3/ε4 genotypes increased in three-vessel-disease patients and the frequency of ɛ2/ɛ2 genotype increased in one-vessel-disease patients. Conclusion : ɛ3/ɛ3 and ɛ3/ɛ4 genotypes are suggested to be predisposing factors, which, in combination with environmental factors, may trigger the degree of luminal narrowing. The possible mechanisms remain elusive and require further studies.

Adenosine Preconditioning versus Ischemic Preconditioning in Patients undergoing Off-Pump Coronary Artery Bypass (OPCAB).

BACKGROUND: During off-pump coronary artery bypass (OPCAB), the heart is subjected to ischemic and reperfusion injury. Preconditioning is a mechanism that permits the heart to tolerate myocardial ischemia. The aim of this study was to compare the effects of Adenosine preconditioning with ischemic preconditioning on the global ejection fraction (EF) in patients undergoing OPCAB. METHODS: In this single-blind, randomized controlled trial, sixty patients undergoing OPCAB were allocated into three equally-numbered groups through simple randomization: Adenosine group, ischemic group, and control group. The patients in the Adenosine group received an infusion of Adenosine. In the ischemic group, ischemic preconditioning was induced by the temporary occlusion of the left anterior descending coronary artery twice for a 2-minute period, followed by 3-minute reperfusion before bypass grafting of the first coronary vessel. The control group received an intravenous infusion of 0.9% saline. Blood samples at different times were sent for the measurement of creatine kinase isoenzyme MB (CK-MB) and cardiac troponin I (cTnI). We also recorded electrocardiographic indices and clinical parameters, including postoperative use of inotropic drugs and preoperative and postoperative EF. RESULTS: History of myocardial infarction, hyperlipidemia, diabetes mellitus, kidney disease, preoperative arrhythmias, and utilization of postoperative inotrope was the same between the three groups. The incidence of postoperative arrhythmias was not significant between the three groups. Also, there were no significant differences in preoperative and postoperative EF and the serum levels of enzymes (cTnI and CK-MB) between the groups. CONCLUSION: Based on the findings of this study, there was no significant difference in the postoperative EF between the groups. Although the incidence of arrhythmias was higher in the ischemic preconditioning group than in the other groups, the difference between the groups did not constitute statistical significance.

Atrial Fibrillation and Early Clinical Outcomes After Mitral Valve Surgery in Patients with Rheumatic vs. Non-Rheumatic Mitral Stenosis.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia after open heart surgery that can lead to early morbidity and mortality following operation. Mitral stenosis (MS) is a structural abnormality of the mitral valve apparatus that can be resulted from previous rheumatic fever or non-rheumatic fever such as congenital mitral stenosis, malignant carcinoid disease etc. This study was designed to test the hypothesis that type of mitral stenosis can affect the incidence, duration and frequency of AF post mitral valve replacement. MATERIALS AND METHODS: We selected fifty patients with rheumatic mitral stenosis and 50 patients with non-rheumatic mitral stenosis who were candidates for mitral valve replacement (MVR) surgery. Pre-operative tests such as CRP, ESR, CBC, UA, ANA, APL (IgM, IgG), ANCA, RF were performed on participants' samples and the type of mitral stenosis, rheumatic or non-rheumatic, was determined clinically. Early post-operative complications such as infection, bleeding, vomiting, renal and respiratory dysfunction etc., were recorded. All patients underwent holter monitoring after being out of ICU to the time of discharge. RESULTS: The mean age of patients was 48.56 ± 17.64 years. 57 cases (57%) were male, and 43 cases (43%) were female. Post-operative AF occurred in 14 cases (14%); 3 cases (6%) in non-rheumatic mitral stenosis group, and 11 cases (22%) in the rheumatic mitral stenosis group. There was a significant relationship between the incidence of AF and type of mitral stenosis (P = 0.02). Renal dysfunction after MVR was higher in rheumatic MS group than in non-rheumatic MS group (P = 0.026). There was no relationship between the type of mitral stenosis (rheumatic or non-rheumatic) and early mortality after mitral valve replacement (P = 0.8). CONCLUSION: We concluded that the type of mitral stenosis affect post-operative outcomes, especially the incidence of atrial fibrillation and some complications after mitral valve replacement.

Perioperative predictors and clinical outcome in early and late ICU discharge after off-pump coronary artery bypass surgery.

The duration of ICU (intensive care unit) stay in cardiac surgery patients has an important role in the rate of complications and costs. The aim of this study was to determine the role of perioperative risk factors in clinical outcome based on the time of ICU discharge. In this descriptive study, 219 patients undergoing off-pump coronary artery bypass (OPCAB) surgery in Afshar Hospital in Yazd, an Iranian city, were divided into early (≤24 hrs) and late (>24 hrs) ICU discharge groups according to the duration of ICU stay. The preoperative, intraoperative and postoperative risk factors, the complications and the outcome were evaluated. Age, sex, hyperlipidemia, diabetes mellitus, previous myocardial infarction, renal failure, cerebrovascular accident, and level of hematocrit and creatinine were not significantly different between the two groups. Patients with hemodynamic instability, respiratory dysfunction, ejection fraction <35%, hypertension, inotrope administration, left main coronary artery involvement, use of intraaortic balloon pump (IABP) and arrhythmia had significantly higher mortality and longer ICU stay (>24 hrs) compared to others (P value <0.05). The duration of intubation was significantly lower in the early discharge group (7.8 ± 3.8 hrs compared to 17 ± 9.9 hrs) than in the late discharge group. Time of ICU discharge depends on perioperative risk factors, and risk factor modification may improve clinical outcome.