Correction to: Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

The original version of this article unfortunately contained a typo in the co-author name.

Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination. 388 individuals receiving PCI were enrolled in this study. Different pretreatment doses of clopidogrel were prescribed under the interventional cardiologists' guidance. The patients were followed for a duration of 1 month, and 6 months. Six SNPs were selected for genotyping including CYP2C19*2 (c.681G > A), CYP2C19*3 (c.636G > A), CYP2C19*17 allele (c.-806C > T), ABCB1 (c.3435C > T), CYP3A5 (c.6986A > G), and CYP3A4 (c.1026 + 12G > A). The mean loading dose was 600 mg/day in 267 (68.8%) individuals, 300 mg/day in 121 (31.2%). 8 patients had cardiovascular events such as thrombosis, unstable angina, and non-STEMI. The studied alleles and genotypes were in Hardy-Weinberg equilibrium. None of the SNPs individually were significantly associated with outcome events. Our results indicate that combinations of different alleles of genes are involved in pharmacokinetic variability and joint factors are important; this means that genotyping and analysis of an individual variant may not be as straightforward in risk assessment and pharmacogenetics. This highlights the importance of personalized medicine in risk assessment and treatment.

Mitral valve resistance determines hemodynamic consequences of severe rheumatic mitral stenosis and immediate outcomes of percutaneous valvuloplasty.

INTRODUCTION: The mitral valve area (MVA) poorly reflects the hemodynamic status of (MS). In this study, we compared the MVA with mitral valve resistance (MVR) with regard to the determination of hemodynamic consequences of MS and the immediate outcomes of percutaneous balloon mitral valvuloplasty (PBMV). METHODS: In a prospective study, 36 patients with severe rheumatic MS with left ventricular ejection fraction (LVEF) >50% were evaluated. They underwent transthoracic echocardiography (TTE) and catheterization. The MVA was measured by two-dimensional planimetry and pressure half-time (PHT), and the MVR was calculated using the equation: 1333 × transmitral pressure gradient mean transmitral diastolic flow rate. RESULTS: The patients' mean age was 47.8±10.5 years. MVR ≥140.6 dynes·s/cm5 detected systolic pulmonary arterial pressure (sPAP) >55 mm Hg with a sensitivity of 100% and a specificity of 74%. The sensitivity and specificity of MVA<0.75 cm2 to discriminate elevated sPAP were 81% and 89%, respectively. PHT ≥323.5 mseconds had a sensitivity of 78% and a specificity of 96% to detect an elevated sPAP. To predict a successful PBMV, preprocedural MVR ≥106.1 dynes·s/cm5 had a sensitivity of 100% and a specificity of 67% (area under the curve [AUC]=0.763; 95% confidence interval [CI]=0.520-1.006; P=.034); preprocedural MVA <0.95 cm2 had a sensitivity of 78% and a specificity of 73% (AUC=0.730; 95% CI=0.503-0.956; P=.065); and preprocedural PHT ≥210.5 mseconds had a sensitivity of 73% and a specificity of 78% (AUC=0.707; 95% CI=0.474-0.941; P=.095). CONCLUSIONS: MVR seems to be more accurate than MVA in determining the hemodynamic consequences of severe MS as determined by sPAP. In addition, preprocedural MVR detected successful PBMVs.

The frequency and importance of chest pain in midterm follow up of transcatheter closure of interatrial septal defect.

Introduction: We evaluated chest pain alongside other midterm subjective and objective complications of the transcatheter closure of atrial septal defects (ASDs) and patent foramen ovales (PFOs) with various closure devices. Methods: This cross-sectional study, performed from March 2010 to October 2015 in Rajaie Cardiovascular, Medical, and Research Center, evaluated 313 patients (mean age = 29.12 ± 10 years, 32.9% male) for probable complications associated with the transcatheter occlusion of secundum ASDs (n = 289, mean age = 30.5 ± 11.4 years, 28% male) or PFOs (n = 24, mean age = 42.8 ± 10.2 years). ASD closure was performed under sedation and transesophageal echocardiography (TEE) guidance. Duration of follow-up was 12 ± 3 months (mean follow-up = 11.52 months). Results: Among the subjective complications, chest pain was the most frequent complaint during the follow-up period and although it was common (7.3%), a clear cardiac etiology was rare. Thirteen (4.2%) patients reported palpitation during the follow-up period, and 4 had documented arrhythmias-including atrial flutter, atrial fibrillation, and 2:1 atrioventricular block. Migraine with or without aura occurred in 1.6% of the patients. Objective complications comprising tamponade, device embolization, and thrombus formation occurred in 6 (1.9%) patients. There was no procedure-related mortality in our patients. Conclusion: Transcatheter closure of PFOs and secundum-type ASDs in our adult patients using ASD septal occluders was associated with a high degree of success, minimal procedural subjective and objective complication rates, and excellent short- and midterm results. Although chest pain was common after the first month following ASD closure, there was no cardiac death or aortic erosion in 11.52 months follow up.

The Effects of Side Branch Predilation During Provisional Stenting of Coronary Bifurcation Lesions: A Double-Blind Randomized Controlled Trial.

BACKGROUND: There is a paucity of data regarding the role of side branch (SB) predilation during the provisional stenting of bifurcation lesions. OBJECTIVES: The present study aimed to assess the effects of SB predilation on the outcomes of true bifurcation interventions. PATIENTS AND METHODS: Sixty patients with true bifurcation lesions according to the Medina classification were included in the study and randomly assigned to receive SB predilation before stenting the main branch (n = 30) or no predilation as the control group (n = 30). RESULTS: There was a trend toward the higher occurrence of dissection in the predilated ostial lesions of the SB compared to the non-predilated group (16.7% vs. 0, P = 0.07). Performance of the SB predilation was not associated with improved flow of the SB or fewer degrees of ostial stenosis after stenting the main branch, the need to rewire, rewiring time, or the rate of use of the final kissing balloon dilation and double stents procedures. CONCLUSIONS: Routine predilation of the SB in provisional stenting of true bifurcation lesions seems to be ineffective and might be associated with some undesirable consequences. Still, there are some complex ostial lesions of the SB which could benefit from predilation.

Coronary Slow Flow Phenomenon Clinical Findings and Predictors.

BACKGROUND: In some patients with chest pain, selective coronary angiography reveals slow contrast agent passage through the epicardial coronary arteries in the absence of stenosis. This phenomenon has been designated the slow coronary flow (SCF) phenomenon. OBJECTIVES: In this study, we aimed to describe the demographic and clinical findings and presence of common atherosclerosis risk factors in patients with the SCF phenomenon. PATIENTS AND METHODS: Between October 2014 and March 2015, demographic data, clinical histories, atherosclerosis risk factors, and laboratory and angiographic findings were recorded for all consecutive patients scheduled for coronary angiography and diagnosed with the SCF phenomenon, as well as a control group (patients with normal epicardial coronary arteries; NECA). SCF was diagnosed based on the thrombolysis in myocardial infarction frame count (TFC). A TFC > 27 indicated a diagnosis of SCF phenomenon. RESULTS: Among the 3600 patients scheduled for selective coronary angiography, 75 (2%) met the SCF criteria. SCF and NECA patients did not exhibit statistically significant differences in traditional risk factors except for hypertension, which was more prevalent in SCF than NECA patients (52% versus 31%, P = 0.008). A multivariable analysis indicated a low body mass index, presence of hypertension, low high-density lipoprotein cholesterol (HDL-c) level, and high hemoglobin level as independent predictors of the SCF phenomenon; of these, hypertension was the strongest predictor (odds ratio = 6.3, 95% confidence interval: 2.2 - 17.9, P = 0.001). CONCLUSIONS: The SCF phenomenon is relatively frequent, particularly among patients with acute coronary syndrome who are scheduled for coronary angiography. Hypertension, a low HDL-c level, and high hemoglobin level can be considered independent predictors of this phenomenon.

Comparison of outcomes of diseased coronary arteries ectasia, stenosis and combined.

BACKGROUND: Coronary artery ectasia (CAE) is a localized or diffuse abnormal dilatation of coronary arteries. Controversy still remains about its cardiovascular events rate, prognosis, and etiology. Adverse effects of CAE coinciding with coronary artery stenosis (CAS) (and in isolated form) are unclear. OBJECTIVES: We aimed to investigate the cardiovascular event rate of CAE in comparison to 'CAS only', and comparing their etiology. PATIENTS AND METHODS: This cross-sectional study was conducted on 200 patients between May 2011 and June 2012. Of them, 40 had CAE (case group) and 160 had only CAS (control group). Patients with CAE were divided into 2 subgroups according to the absence (E1) or presence (E2) of CAS. They were followed up for at least 6 month for cardiovascular events, including death, unstable angina and myocardial infarction (MI). Finally, we compared findings in CAE, CAS, and E1 and E2 subgroups and evaluated the relationship between severity of ectasia (1-1.5 times, 1.5-2 times, and > 2 times) and CAS. RESULTS: Hypertension (HTN), dyslipidemia (DLP), and male sex were matched in both groups without significant difference. Cigarette smoking (C/S) was significantly higher and diabetes mellitus (DM) was significantly lower in CAE compared to CAS patients. A subgroup of CAE patients with CAS (E2 subgroup) had significantly higher mortality rate than isolated CAS (P = 0.043). MI was seen in several isolated CAE patients (E1) subgroup. Severity of ectasia showed no significant relationship with CAS. CONCLUSIONS: Presence of CAE in patients with CAS increases its cardiovascular event rate. Isolated CAE is not a benign finding and MI can occur. Risk factors of CAE are similar to CAS, but C/S is more associated with CAE than CAS. DM is seen in CAE patients less than CAS.

Association of polymorphisms at LDLR locus with coronary artery disease independently from lipid profile.

Coronary artery disease (CAD) is the leading cause of mortality in many parts of the world. Genome-wide association studies (GWAS) have identified several genetic variants associated with CAD in Low-density lipoprotein receptor (LDLR) locus. This study was evaluated the possible association of genetic markers at LDLR locus with CAD irrespective to lipid profile and as well as the association of these SNPs with severity of CAD in Iranian population. Sequencing of 2 exons in LDLR gene (Exon 2, 12) and part of intron 30 of SMARCA4 gene include rs1122608, was performed in 170 Iranian patients angiographically confirmed CAD and 104 healthy controls by direct sequencing. Sullivan's scoring system was used for determining the severity of CAD in cases. Our results showed that homozygote genotypes of rs1122608 (P<0.0001), rs4300767 (P<0.005) and rs10417578 (p<0.007) SNPs have strong protective effects on the CAD. In addition, we found that rs1122608 (GT or TT) was at higher risk of three vessel involvement compared to single vessels affecting (P=0.01).

Coronary Flow Assessment in Unstable Angina/non ST-segment Elevation Myocardial Infarction Patients via Thrombolysis in Myocardial Infarction Frame Count in Angiography.

BACKGROUND: TIMI Frame Count (TFC) is one of the methods to estimate the coronary blood flow velocity. This is a simple, inexpensive, quantitative, reproducible, and continuous variable method. Many studies have been conducted on TFC assessment in ST elevation myocardial infarction (STEMI) patients. OBJECTIVES: The present study is aimed to measure the TFC in the coronary arteries of UA/NSTEMI patients to find abnormalities in diseased or patent vessels and compare with the normal values. PATIENTS AND METHODS: The participants were 105 consecutive UA/NSTEMI patients who underwent coronary angiography in Shahid Rajaie Cardiovascular Medical and Research Center, Tehran, Iran in 2009. Exclusion criteria were history of CABG, PCI, or STEMI or presence of occluded arteries in angiography. We measured the coronary TFC in these patients. We examined also 55 stable patients without coronary lesions and with TIMI 3 flow to have an estimation of normal TFCs. RESULTS: From a total of 105 patients, 25 (23.8%) had no significant coronary lesion (> 60%); 35 (33.3%) were diagnosed with single vessel disease; 22 (21%) were 2VD; and 23 (21.9%) were 3 VD.). In overall, mean TFC in UA/NSTEMI group was 28.7 (± 14) frames compared to 23.8 (± 7.8) frames in the normal group (P < 0.05). In the vessels with significant lesions, TFC was significantly higher than normal (30.84 vs. 23.8; P < 0.001) and also significantly higher than patent vessels of the same patients (30.84 vs. 26.10; P = 0.029). In these patients, patent vessels had higher TFC values compared to normal coronaries (26.10 vs. 23.8), but the difference was not significant (P = 0.12). In the patients with significant lesions, mean TFC was higher than the same value in acute coronary patients without significant lesions (29.3 vs. 27.2), but the difference was not significant (P = 0.114). In the patients who underwent PCI and stenting, TFC changed significantly after PCI toward the normal value (P = 0.001). In the patients with elevated cardiac enzymes, TFC was higher but the difference was not significant (P = 0.35). CONCLUSIONS: Patent coronaries of UA/NSTEMI patients have a trend to higher TFCs compared to normal values. Presence of significant coronary lesions in these patients significantly increases TFC.

Evaluation of Percutaneous Coronary Intervention and stenting of Left Main Coronary Artery Stenosis in Tehran's Rajaie and Lavasani Hospitals from 2010 to 2011.

BACKGROUND: Data of the results from treatment of unprotected and protected LMCA diseases with PCI and stent implantations in our country were limited. Surgical therapy is considered as an standard care for patients with unprotected LMCA stenosis. This notion is based on some randomized and observational studies performed three decades ago which convincingly showed superiority of CABGs over medical therapy. Moreover, preliminary studies have shown that the use of DES for the treatment of unprotected LMCA diseases is associated with very favorable mid-term outcome, which is highly competitive with that of surgery, especially for ostial lesions. OBJECTIVES: This study sought to evaluate one year safety and effectiveness of PCI and stenting in LMCA disease. PATIENTS AND METHODS: We performed a one year clinical follow-up of any patients with LMCA disease "Protected and Unprotected" who underwent PCI and stenting (n = 40) with BMS (n = 17) or DES (n = 23) in Tehran's Rajaje and Lavasani hospitals from September 2010 to September 2011. The primary end points were all-cause mortality, and MACCE which consisted of the composite of death, MI, stroke, and target vessel revascularization, and the duration of hospitalization change the severity of angina pain and the function class of physical activity. RESULTS: In the one year follow-up, the adjusted risk of death was 5% and the composite of death, MI, stroke and target vessel revascularization (MACCE) was 22%. In 94.7% the number of patients, the severity of angina pain were decreased, and in 92.5% of patients, the function class of physical activity has been improved. The duration of hospitalization was 4.38 ± 1.63 days which was less than that of CABGs. CONCLUSIONS: For the treatment of protected and unprotected LMCA diseases, PCI with stent implantation is effective, and leads to decreasing the mortality and the death rate, MI, stroke, the severity of angina pain, and improving the function class of physical activity and tolerance.

Effect of garlic powder tablet on carotid intima-media thickness in patients with coronary artery disease: a preliminary randomized controlled trial.

BACKGROUND/OBJECTIVES: This study was designed to investigate whether garlic powder tablets in adjunct to conventional medical treatment could have an effect on carotid intima-media thickness (CIMT) and plasma lipoproteins and lipids in patients with coronary artery disease (CAD). SUBJECTS/METHODS: A randomized, placebo-controlled, clinical trial was conducted on 56 patients with CAD between the ages of 25 and 75 years. The patients were randomly divided into two groups: garlic group (n = 27), receiving garlic powder tablet (1200 µg allicin/tab) twice daily and the placebo group (n = 29), receiving placebo for 3 months. The rate of atherosclerosis progression was measured by B-mode ultrasonography as the increase in CIMT. RESULTS: After 3 months of taking garlic tablets, CIMT values had minor variations (0.009 ± 0.007 mm reduction from baseline), while in the placebo group, an increase in CIMT values was observed (0.04 ± 0.01 mm increase from baseline). After 3 months of treatment, mean CIMT difference from baseline was significantly differ between the two groups (p < 0.001). Plasma lipids and lipoproteins (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, Apolipoprotein A1 and Apolipoprotein B) did not differ between the two groups. CONCLUSIONS: The results suggest that dry garlic powder tablet is superior to placebo in prevention of CIMT progression in patients with CAD and may be considered as an adjunct treatment for atherosclerosis.

Diagnostic value of electrocardiography compared with echocardiography in measuring left ventricular mass index in major thalassemia patients over 10 years of age.

BACKGROUND: Patients suffering from major beta thalassemia need frequent blood transfusions and, if not treated well, would be at risk of heart dysfunction. This study was performed to determine the diagnostic value of electrocardiography versus echocardiography in measuring the left ventricular mass index in these patients. METHODS: Between July 2010 and June 2011, 82 asymptomatic patients over 10 years of age with major thalassemia (42 men with a mean age of 17.65 ± 3.39 years and 40 women with a mean age of 16.9 ± 3.38 years) were enrolled in this study. For all the patients, standard electrocardiography (to measure R in aVL and S in V3 and calculate left ventricular mass index by electrocardiography) and echocardiography (to measure interventricular septum diameter in diastole, left ventricular posterior wall diameter in diastole, and left ventricular diameter in diastole in order to calculate left ventricular mass index by echocardiography) were performed, at least one week after transfusion. The calculated left ventricular mass indices were thereafter compared between the two methods (electrocardiography and echocardiography). RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value in the two techniques in determining the left ventricular mass index were 67%, 25%, 89%, and 7% in the females, 65%, 33%, 92%, and 6% in the males, and 67%, 14%, 89%, and 3% in the total population, respectively. Furthermore, this study demonstrated that the average left ventricular mass index by echocardiography and electrocardiography was 104.86 ± 21.65 gr/m2 and 91.69 ± 12.03 gr/m2, respectively. Echocardiography was much more accurate than electrocardiography in determining the left ventricular mass index (p value = 0.0001). CONCLUSION: The findings of this study demonstrated that echocardiography was more accurate and more reliable than electrocardiography in determining the left ventricular mass index in major thalassemia patients.

Percutaneous device closure for secundum-type atrial septal defect: short and intermediate-term results.

BACKGROUND: Device closure of an isolated secundum type atrial septal defect (ASD) has been used as an alternative method for open surgical closure with comparable success and lower morbidity. In this study we evaluated the procedural success and mid-term follow-up results of percutaneous closure of secundum ASD with an Amplatzer™Septal Occluder(ASO) device or a Figula ASD occluder device. METHODS: From June 2001 to January 2009, 74 consecutive patients were scheduled for percutaneous device closure in two centers in Tehran, Iran. All patients had a stretched defect diameter of 30mm or less. After using a sizing balloon to measure the stop-flow diameter, device implantation was performed under the guidance of a trans-esophageal echocardiography (TEE).The size was generally 1 - 2 mm larger than the stretched diameter. Patients were followed for an average of 11 ±4 months. RESULTS: The median stretched diameter of the defect was 20.7±4.8 mm (range: 8 - 30 mm).A total of 73 devices were used in this study. Device closure was successful in 72 (97.2%) out of 74 patients. Repositioning of the device was required in one patient. Major complications(including significant residual shunt and device embolization) occurred in 3 (4%) patients.There was no procedure-related mortality in our patients. Mild-to-moderate residual shunt was detectable in 10 (13.7%) patients immediately following the procedure and in 5 (6.7%) patients 24 hours after the procedure. None had residual flow across the device at the end of the follow-up period. CONCLUSION: Device closure of ASD has a safety profile comparable to open surgical repair and can effectively close the defect with excellent procedural and mid-term results.

relationship between distribution of coronary artery lesions and renal artery stenosis in patients undergoing simultaneous coronary and renal angiography.

AIMS: We evaluated the relationship between distribution of lesions in coronary tree and atherosclerotic renal artery stenosis (RAS). METHODS AND RESULTS: Data collected prospectively on 500 consecutive patients who underwent simultaneous renal angiography following coronary angiography. Overall prevalence of RAS was 26.2% (131 patients). Significant (≥50% luminal diameter stenosis) RAS was present in 70 patients (14%). In 346 individuals of the study population, significant CAD was present (69.2%). Significant RAS was more common (18.4%) in this group. Older age, higher intra-arterial systolic blood pressure (SBP) and pulse pressure (PP) at the time of catheterization, and 3-vessel coronary artery disease (CAD) were associated with significant RAS in univariate analysis. Relationship between involved locations of coronary arteries [Left anterior descending (LAD), left circumflex (LCX), Right Coronary Artery (RCA), and their ostio-proximal portions] and RAS were significant except for left main (LM) disease. In multivariate model, age more than 62 years, SBP greater than 150 mmHg, PP in excess of 60 mmHg and RCA involvement were independent predictors of significant RAS. CONCLUSION: Simultaneous renal angiography following coronary angiography might be justified in patients with significant RCA disease who are older with increased levels of intra-arterial SBP and PP.