Whole-exome sequencing uncovers a novel EFEMP2 gene variant (c.C247T) associated with dominant nonsyndromic thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a multifactorial disorder. Familial TAA, which is more clinically aggressive, is associated with a high risk of lethal dissection or rupture. Genetic evaluation can provide TAA patients with personalized treatment and help in predicting risk to family members. OBJECTIVE: The purpose of this investigation was to report a likely pathogenic variant in the EFEMP2 gene that may contribute to TAA in a family with a documented history of the condition. METHODS: In the index patient, the causative genetic predisposition was identified using whole-exome sequencing. The potential likely pathogenic effect of the candidate variant was further analyzed through bioinformatics analysis, homology modeling, and molecular docking. RESULTS: The results revealed a likely pathogenic heterozygous variant, c.247C>T p.Arg83Cys, in exon 4 of the EFEMP2 gene (NM_016938), which was predicted to have disease-causing effects by MutationTaster, PROVEAN, SIFT, and CADD (phred score = 27.6). CONCLUSION: In this study, a likely pathogenic variant in the EFEMP2 gene was identified in an Iranian family with a dominant pattern of autosomal inheritance of TAA. This finding underscores the importance of conducting molecular genetic evaluations in families with nonsyndromic TAA and the significance of early detection of at-risk family members.

Safety of older generations of gadolinium in mild-to-moderate renal failure.

Nephrogenic systemic fibrosis (NSF) is a rare disease that is mostly reported in patients with chronic kidney disease (CKD) who have received gadolinium as a contrast in imaging techniques. The exact pathogenetic role of renal failure or gadolinium is not known. The aim of this study is to show whether mild-to-moderate renal failure is a risk for NSF as it is described in severe renal failure. In this cross-sectional study, we enrolled 164 patients with serum creatinine levels >1.5 mg/dL who were in different stages of CKD and had received gadolinium (gadopentetate). The average lag time between the gadolinium administration and the study was 4 months. The most prevalent skin symptom was itching (19%) and the least frequent was induration and papules (<1%). At the follow-up, all skin lesions were relieved. No patients had characteristic lesions of NSF. Twenty-five percent of patients had acute kidney injury at the time of gadolinium exposure. No patients had liver disease and only five were receiving erythropoietin. None of our patients were taking immunosuppressive agents, but all of them suffered from cardiovascular diseases. We conclude that in patients with mild-to-moderate renal failure, it seems that gadolinium is associated with no or very low risk for NSF. We did not find any NSF in patients with severe renal failure. However, because of the rarity of NSF, the low number of such patients in the study, and the high mortality, the use of gadolinium in these patients should be avoided.

Clinical features, management and in-hospital outcome of ST elevation myocardial infarction (STEMI) in young adults under 40 years of age.

OBJECTIVES: This study was designed to evaluate the demographic and clinical findings and in-hospital management and outcome in patients with an acute ST-segment elevation myocardial infarction (STEMI). MATERIAL AND METHODS: By review of the Cardiovascular Tehran Heart Center Registry (CVDTHCR), 2028 patients were found to have the acute STEMI. We compared the patients' characteristics in 109 (5.4%) subjects < or = 40 and 1919 subjects > 40-years-old. RESULTS: The young patients had less diabetes, hypertension, dyslipidemia and history of MI or prior revascularization, and were more likely to be male (92.7% vs. 74%), smoker (58.7% vs. 31.7%) and have family history of CVD (50.5% vs. 23.4%). The young patients had higher prevalence of angiographically normal coronary artery (13.7% vs. 0.9%; p<0.001). The young patients were more likely to undergo percutaneous coronary intervention (38.5% vs. 18.6%), whereas coronary artery bypass grafting was more common in the old ones (p<0.001). In-hospital death was markedly different among young and old patients (0.9% and 6.1%, respectively; p<0.01). CONCLUSION: In STEMI population, the risk profile, clinical findings and severity of coronary disease of the young differ substantially from the elderly counterparts. Young patients with STEMI have a favorable outcome compared with that in older patients.

Metabolic syndrome: stronger association with coronary artery disease in young men in comparison with higher prevalence in young women.

BACKGROUND: Being overweight, a constituent of the metabolic syndrome, is also an important contributing factor to the development of coronary artery disease in younger patients, compared with the older patient population. Owing to the above-mentioned fact, we sought to assess the association of the metabolic syndrome with premature coronary artery disease. METHODS: In an analytic cross-sectional study, 940 patients (553 women

Stent-graft exclusion of multiple symptomatic coronary artery fistulae.

Coronary artery fistulae may be congenital or acquired abnormalities in which blood is shunted into a cardiac chamber, great vessel, or other structure, bypassing the myocardial capillary network. Patients with coronary artery fistulae may present with dyspnea, congestive heart failure, angina, endocarditis, arrhythmias, or myocardial infarction. Symptomatic patients must be treated in order to prevent such complications as sudden death or myocardial infarction. Surgery is the gold standard for closure of these lesions; however, an increasing number of reports have shown that percutaneous closure may be a safe and effective alternative. We report the successful percutaneous exclusion of multiple coronary artery-to-pulmonary artery fistulae by means of several balloon-expandable stent-grafts in a patient who had a history of coronary artery bypass surgery and symptoms of congestive heart failure.

Two ecstasy-induced myocardial infarctions during a three month period in a young man.

Ecstasy normally contains 3,4 methylenedioxymethamphetamine (MDMA) that increases the levels of serotonin, dopamine, and epinephrine in the central nervous system with consequent adverse effects on the cardiovascular system. Herein, we presented a case of ecstasy abuse which resulted in two episodes myocardial infarction during a three month period; the second episode led to death due to thrombus formation.

QT Dispersion and Age; Independent Predictors of Restenosis after Percutaneous Coronary Intervention.

INTRODUCTION: There are no reliable non-invasive markers of restenosis after Percutaneous Coronary Interventions (PCIs). The aim of our study was to measure changes incorrected QT interval (QTc), corrected QT dispersion (QTcd), corrected T wave peak to end interval (TPEc) and corrected TPE dispersion (TPEcd) after PCI and to determine whether restenosis subsequently affects these indices. METHODS: From 211 patients, who underwent successful PCI, 202 patients were referred for repeated coronary angiography in order to exclusion of coronary restenosis and included in this analysis. QTc, QTcd, TPEc and TPEcd indices were calculated just before PCI and 24 hours later. RESULTS: Comparing pre procedural with post procedural results, median QTc and median QTcd decreased significantly after PCI procedure (from 447 to 440 ms, p=0.017 and from 46 to 40 ms,p=0.005; respectively). Corresponding changes of TPEc and TPEcD were not statistically significant. Multivariate analysis showed higher amounts of QTcd changes [Exp(B): 1.033, 95% CI: 1.018-1.051; P=0.025] and younger age[Exp(B): 1.074, 95% CI: 1.038-1.112; P=0.023] as independent predictors of restenosis. Area under the ROC curve indicated good predictive performance of QTcd changes (.QTcd) [AUC: 0.71, 95% CI: 0.51-0.86, P = 0.03] and age [AUC 0.68, 95% CI 0.62-0.74, p = 0.04] for restenosis after PCI. The best cut-off point for .QTcd was 6 msec, and for age was 52 years. The sensitivity and specificity of .QTcd.6 ms to detect coronary restenosis were 73.2% and 71.4% respectively. The diagnostic accuracy of age was also similar, the sensitivity and specificity of age. 52 years were 68.1% and 74.3% respectively. CONCLUSION: The Higher differences between pre and post PCI QTcd may be an inexpensive and simple predictor of restenosis after a previously successful coronary angioplasty. It seems that these findings encourage us to re-think about using QTcd as a simple ECG predictor for sustained coronary patency after angioplasty.

Homocysteine, vitamin B12 and folate levels in premature coronary artery disease.

BACKGROUND: Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD. METHODS: We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran. RESULTS: After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 +/- 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia. CONCLUSION: We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (below 45 years old)--especially in men--and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.

Relationship Between Red Blood Cell Distribution Width and Mortality of Patients with Acute Myocardial Infarction Referring to Tehran Heart Center.

OBJECTIVE: Coronary heart disease is the most common cause of death in most countries and also in Iran. Among novel prognostic markers suggested in recent studies for coronary heart disease, red blood cell distribution width (RDW) has been found to be associated with poor prognosis. Therefore, we aimed to evaluate the relationship between RDW and 6-month mortality and cardiovascular events after the initial attack of myocardial infarction (MI). METHODS: Medical records of 642 patients with MI were investigated for basic and clinical characteristics, as well as patients' first hemoglobin, RDW, and mean corpuscular volume at the time of admission. Then based on patients' time of hospitalization, they were followed up by telephone for readmission and mortality 6 months later. RESULTS: Mean ± SD age of patients was 62.7 ± 12.7 years. In 6-month telephone follow-up, 443 patients (69%) had readmission. Six-month mortality occurred in 70 patients (10.9%). Patients with RDW level of 14.6% and higher were significantly older (P < 0.001). Three percent of patients with low RDW and 14.8% in high RDW group had renal failure (P < 0.001). Six-month mortality was observed in 24.3% of patients with high RDW and 7.9% of those with low RDW (P < 0.001). In multivariate logistic regression analysis, RDW (odds ratio: 1.98, 95% confidence interval: 1.06-3.68, P = 0.03), age, and ejection fraction were significant independent prognostic factors for mortality. CONCLUSIONS: Six-month mortality was significantly higher in patients with MI with high RDW. Thus given that RDW is an inexpensive and available laboratory test, it could be used for mortality risk assessment and follow up the patients for stricter control of other modifiable risk factors.

Mean Platelet Volume as a Predictor of One-Year Major Adverse Cardiac Events following Elective Percutaneous Coronary Interventions.

BACKGROUND: Mean platelet volume (MPV) correlates with platelet activity. The relation between MPV and long-term outcome in patients undergoing percutaneous coronary intervention (PCI) has been investigated in several studies. The aim of the present study was to investigate the utility of MPV in prognosticating the long-term outcome after elective PCI. METHODS: The study cohort included 2627 patients undergoing elective PCI between September 2008 and June 2010, whose baseline MPV measurements before PCI were available. The patients were divided into three groups of MPV < 9.1 fL, MPV = 9.1 to 10 fL, and MPV > 10 fL, and they were assessed for developing major adverse cardiac events (MACE), comprising death, myocardial infarction (MI), target vessel revascularization (TVR), and target lesion revascularization (TLR) over a one-year follow-up. RESULTS: Of 2539 patients, major adverse cardiac events (MACE) at one year occurred in 77 (3.0%) patients, including mortality in 26 (1.0%). The patients in the highest tertile (MPV > 10 fL) had no increased frequency of MACE compared to those in the mid (9.1 to 10 fL) and lowest (< 9.1 fL) tertiles (3.3%, 2.2%, and 3.8%, respectively; p value = 0.14). No significant differences were found for each of the primary endpoints among the MPV tertiles. In multivariate logistic regression, we investigated the association between high MPV and total MACE (OR = 1.10, 95%CI: 0.69-1.77; p value = 0.68), death (OR = 1.14, 95%CI: 0.51-2.54; p value = 0.74), and non-fatal MI (OR = 1.85, 95%CI: 0.73-4.67; p value = 0.19) at one year's follow-up but MPV did not remain in the model in any of the cases. In the diabetic patients, the one-way analysis of variance demonstrated that mortality was 1.6% (4 patients) in the highest tertile, 0.8% (2 patients) in the mid tertile, and 0.5% (one patient) in the lowest tertile. CONCLUSION: There was no direct correlation between pre-procedural MPV and MACE in elective PCI. MPV can only be considered as an appropriate factor for predicting mortality in diabetic patients undergoing elective PCI.

A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients.

OBJECTIVE: A significant correlation exists between coronary artery diseases and depression. The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention (PCI). METHODS: In this randomized double-blind parallel-group study, 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were randomized to receive either fluoexetine (40mg/day) or saffron (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were systemically recorded. RESULTS: By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores (P=0.62). Remission and response rates were not significantly different as well (P=1.00 and P=0.67; respectively). There was no significant difference between two groups in the frequency of adverse events during this trial. LIMITATIONS: Relatively small sample size and short observational period were the major limitations of this study. CONCLUSION: Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression.

Comparing angiography features of inferior versus anterior myocardial infarction regarding severity and extension in a cohort of Iranian patients.

BACKGROUND: The location of acute myocardial infarction (MI) is an important prognostic factor for risk stratification of patients with first ST-segment elevation MI (STEMI). The main goal of this study was to compare the severity and extension of coronary involvement in inferior and anterior MI. METHODS: This study reviewed angiographic reports of 579 patients with a first anterior wall STEMI and 690 with a first inferior STEMI that were referred to Tehran Heart Center between March 2004 and September 2007. The number of coronary vessels involvement and the presence of left main lesion were determined based on angiography reports. The Gensini score was also calculated for each patient from the coronary arteriogram. RESULTS: Incidence of left main lesion was similar between the two groups. Although coronary arteries involvement according to Gensini score was more severe in anterior wall MI group compared with inferior wall MI group, the number of involved coronary arteries was significantly higher in the inferior MI patients. Recommendation of coronary artery bypass grafting, percutaneous coronary intervention (PCI) or medical treatment were the same for both groups; however, patients with anterior MI were treated more with primary PCI. CONCLUSIONS: According to our angiography database, despite anterior wall MI is associated with more severity of coronary artery disease; inferior wall MI is more extent with regard to the number of involved coronary vessels. Location of MI can predict the severity and extension of infarction.

Complex carotid stenting using a coronary technique.

PURPOSE: To report the utility of a coronary technique to facilitate carotid stenting in patients with difficult arch anatomies. TECHNIQUE: When confronted with challenging arch anatomy that prevents engaging the common carotid artery (CCA) with the guiding sheath using standard techniques, an 8-F left Amplatz guiding catheter (AL1) is placed at the origin of the innominate artery. A 0.014-inch coronary guidewire is advanced into the external carotid artery (ECA), and a small monorail coronary balloon is inflated in a small branch of the ECA. The balloon/guidewire combination facilitates maneuvering a 0.035-inch Amplatz super-stiff guidewire through the ECA and then advancing the guiding catheter into the CCA. CONCLUSION: This anchoring technique can be a helpful method for cannulating the CCA in patients with a complex arch when the ECA is patent.

The association of opium with coronary artery disease.

BACKGROUND: The effects of opium consumption on coronary artery disease are still unknown. METHODS: A cross-sectional study was conducted on 2405 patients admitted to the Angiographic Ward at Tehran Heart Center from 7 May 2005 to 13 August 2005. RESULTS: After adjusting for conventional cardiovascular risk factors, opium consumption was a significant risk factor for coronary artery disease (P=0.01 and odds ratio=1.8). Moreover, the amount of opium consumption was associated significantly with the severity of coronary atherosclerosis, as measured by clinical vessel score (r=0.2, P=0.002). CONCLUSIONS: To our knowledge, this is the first time that the adverse effects of opium consumption on coronary arteries was defined.