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Cynthia Al Hageh,1,&ast; Stephanie Chacar,2,&ast; Thenmozhi Venkatachalam,2 Dominique Gauguier,3,4 Antoine Abchee,5 Elie Chammas,6 Hamdan Hamdan,2 Siobhan O’Sullivan,1 Pierre Zalloua,1,7,8 Moni Nader2,7 1Department of Molecular Biology and Genetics, College of Medicine and Health Sciences, Khalifa University for Science and Technology, Abu Dhabi, United Arab Emirates; 2Department of Physiology and Immunology College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, UAE; 3McGill University and Genome Quebec Innovation Centre, Montreal, QC, H3A 0G1, Canada; 4Université Paris Cité, INSERM, Paris, France; 5Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; 6School of Medicine, Lebanese University, Beirut, Lebanon; 7Biotechnology Center, Khalifa University for Science and Technology, Abu Dhabi, United Arab Emirates; 8Harvard T.H. Chan School of Public Health, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Pierre Zalloua; Moni Nader, College of Medicine and Health Sciences, Khalifa University for Science and Technology, PO Box 127788, Abu Dhabi, United Arab Emirates, Email pierre.zalloua@ku.ac.ae; moni.nader@ku.ac.aeBackground and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design.Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD > 50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD > 50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9.Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value < 0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 (PHACTR1) and rs264 (LPL) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men.Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.Keywords: PHACTR1, LPL, diabetes, restenosis

Cynthia Al Hageh,1,* Stephanie Chacar,1,2,* Michella Ghassibe-Sabbagh,3 Daniel E Platt,4 Andreas Henschel,5 Hamdan Hamdan,1,2 Dominique Gauguier,6,7 Yara El Murr,3 Eman Alefishat,8,9 Elie Chammas,10 Siobhán O’Sullivan,1 Antoine Abchee,11 Moni Nader,2,9 Pierre A Zalloua1,9,12 1Department of Molecular Biology and Genetics, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 2Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 3Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon; 4Computational Biology Center, IBM TJ Watson Research Centre, Yorktown Hgts, NY, USA; 5Department of Electrical Engineering and Computer, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 6Université Paris Cité, INSERM UMR 1124, Paris, 75006, France; 7McGill University and Genome Quebec Innovation Centre, Montreal, QC, H3A 0G1, Canada; 8Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 9Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates; 10School of Medicine, Lebanese University, Beirut, Lebanon; 11Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; 12Harvard T.H. Chan School of Public Health, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Pierre A Zalloua; Moni Nader, College of Medicine and Health Sciences, Khalifa University for Science and Technology, PO Box 127788, Abu Dhabi, United Arab Emirates, Email pierre.zalloua@ku.ac.ae; moni.nader@ku.ac.aeBackgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis.Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries.Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥ 35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with > 50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD.Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.Keywords: lipoprotein(a), cardiovascular diseases, stenosis

Background and Objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase ( MTHFR ). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes., Methods and Results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 μmol/L for hypertensive subjects compared to 11.9 ± 0.173 μmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles., Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Many hemodynamic parameters provide limited information regarding obstructive coronary artery disease (CAD) during exercise stress testing particularly when exercise is suboptimal. Hemodynamic gain index (HGI) is a recent sensitive indicator of ischemia and has been associated with increased mortality. This study evaluated the clinical impact of HGI in patients who underwent concomitant exercise stress testing and coronary computed tomography angiography (CCTA)., Methods: A total of 284 consecutive patients from the executive health program between 2010 and 2018 were identified. Resting and peak heart rate (HR) as well as systolic blood pressure (SBP) measurements were recorded. Framingham risk score (FRS), Duke treadmill score (DTS) and HGI [Formula: see text] were calculated. The latter was divided into quartiles. CCTA was used as a reference test to detect any CAD. Multivariate analysis and artificial neural network were used to determine the independent predictors of obstructive CAD., Results: Mean age was 53 ± 12 years with 83% male. Mean HGI was 1.74 ± 0.67, with cut-off value of severely blunted HGI ≤ 1.25 (Quartile 4). Patients with severely blunted HGI were older, had higher FRS, and worse DTS. Patients with obstructive CAD had lower HGI when compared to those with normal CCTA/non-obstructive CAD (1.36 ± 0.53 vs. 1.77 ± 0.67, P = 0.005), and showed a higher prevalence of severely blunted HGI (44% vs. 22%, P = 0.019). After adjusting for traditional risk factors, HGI remained an independent predictor of obstructive CAD while severely blunted HGI was associated with threefold increased odds of having obstructive CAD (P = 0.05). Using artificial intelligence analysis, severely blunted HGI independently predicted obstructive CAD with an area under the curve of 0.83 and 0.96, and normalized importance of HGI of 100% and 63%, respectively for different models., Conclusions: Among patients who underwent concomitant exercise stress testing and CCTA, severely blunted HGI independently predicted obstructive CAD after multivariate adjustment for traditional risk factors., (© 2023. The Author(s).)

Non-invasive myocardial work (MW) indices are superior to global longitudinal strain (GLS) to assess left ventricular (LV) mechanics in situations where afterload is abnormally high. The rotational motion of the apex provides an accurate index of LV contractility. To date, there are no data about MW values during stress echocardiography (SE), particularly for the apex. Our study aims at assessing MW indices at peak exercise to better understand LV mechanics in patients with high peak systolic blood pressure (SBP). A total of 81 patients without structural or ischemic heart disease referred for SE between January and June 2019 were included. BP measurements, GLS and MW indices were performed at rest and peak exercise. In order to quantify the role of the apex, apical work fraction (AWF) was also calculated and further stratified by peak SBP. A peak SBP > 180 mmHg was considered abnormally high. There were 36 (44%) patients who had peak SBP > 180 mmHg. They showed similar resting GLS and MW values when compared to control. However, peak stress global work index, constructive work and wasted work (GWW) increased significantly (P-value < 0.05), with a relatively constant global work efficiency. In the multivariate analysis, peak SBP > 180 mmHg was associated with threefold increased odds of abnormal peak GWW > 96.5 mmHg% (median value) (odds ratio 3.0, P-value 0.003). Apical work increased significantly when stratified by peak SBP (P-value 0.003) and AWF increased from 33 ± 3% to 37 ± 3% (rest-stress), P-value < 0.0001, but remained constant when stratified by peak SBP. Our analysis provides new data on MW indices at peak stress, particularly for patients with abnormal peak SBP response, and supports the role and the contribution of the apex to MW.

Background: Assessment of diastolic dysfunction (DD) by echocardiography is an integral part of the evaluation of patients with normal ejection fraction and symptoms suggestive of heart failure. However, many patients with DD are asymptomatic. Computed tomography calcium scoring (CTCS) is often used to assess patients at low-intermediate risk for coronary artery disease (CAD). The purpose of this study was to evaluate the association of DD with subclinical coronary artery calcification., Methods: Consecutive patients presenting for executive checkup who underwent resting transthoracic echocardiography followed by CTCS were retrospectively identified between January 2010 and December 2014. Two-dimensional and tissue Doppler imaging parameters were analyzed for assessing and grading of DD. Coronary artery calcium (CAC) score was quantified., Results: A total of 191 patients (mean age 52 ± 12 years, 17% age ≥65, 20% with diabetes) were included. Of them, 69 (36%) patients had DD. Patients with higher CAC score were older, had more comorbidities, lower e', and were more likely to have DD. In the multivariate analysis, DD alone, age >65 years, or both were associated with almost threefold increase of subclinical atherosclerosis. After propensity analysis, DD was still associated with increased odds ratio (OR) for subclinical CAC (OR 3.66 [1.54-8.72], P-value .03) and similarly for e' < 10 cm/s. Compared to patients age <65 years and normal diastolic function, those age >65 years or DD had OR 3.49 (1.45-8.35) (P-value .005) for subclinical coronary atherosclerosis (CAC > 0), whereas those age >65 and DD had OR 9.30 (2.00-42) (P-value .004)., Conclusions: Our analysis suggests that DD was strongly associated with CAC > 0, particularly among those age <65 years. Assessment of CAC as part of the routine clinical evaluation of patients with normal EF and atypical symptoms without a history of coronary atherosclerotic disease is warranted for further risk stratification., (© 2020 Wiley Periodicals, Inc.)

Background: Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D., Introduction: Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial., Methods: This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories., Results and Conclusion: The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Computed tomography coronary angiography (CTCA) has a higher negative predictive value (NPV) for coronary artery disease (CAD) than stress echocardiography (SE). CT calcium scoring (CTCS) allows detection and quantification of coronary artery calcification (CAC). The NPV of combined SE and CTCS for CAD is not well defined. Consecutive patients from the executive screening program who underwent exercise SE and concomitant CTCA were retrospectively identified between January 2010 and December 2014. Patients with normal SE and CAC score of zero were determined, and the presence or absence of any CAD (obstructive or non-obstructive plaques) on CTCA was confirmed. The NPV of combined SE and CTCS was then re-tested using a validation cohort of subsequent consecutive patients enrolled between January 2015 and July 2018. The initial cohort consisted of 173 patients (19% age > 65 years, 19% diabetic); 40% had normal CTCA, 48% with non-obstructive CTCA (77 with CAC score > 0), and 12% with obstructive CTCA (all with CAC score > 0). There were 16 (9.2%) patients with inducible ischemia on SE. A normal SE had a 93% NPV to exclude obstructive CAD but only 42% NPV to exclude any CAD. A combined normal SE and CTCS had a 100% NPV for obstructive CAD, and 92% for any CAD. In a validation cohort of 111 patients, a normal SE and CAC score of zero had NPV of 100% for obstructive CAD and 92% for any CAD. The combined cohort consisted of predominately low Framingham risk patients; more than 40% (70/181) had CAC score > 0 and 5/70 had obstructive CAD, with the remaining non-obstructive. A concomitant normal SE and CAC score of zero excluded obstructive CAD (NPV 100%) and any CAD in 92% of the testing and validation cohorts. CTCS seems to add incremental risk stratification, particularly for patients with low Framingham score.

Background: The 2010 revised Task Force criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) provided guidance for the classification of patients as definitive, borderline or possible ARVC. However, many patients with clinical suspicion for ARVC have isolated RV dyskinetic segments only and partly meet cardiac magnetic resonance (CMR) imaging criteria. This subgroup of patients and the implication of this imaging finding remain not well defined., Methods: There were 65 consecutive patients with clinical suspicion for ARVC who were referred for CMR between 2015 and 2017. The presence of fatty infiltration and fibrosis were assessed using T2 imaging and myocardial delayed enhancement sequences, respectively. RV wall motions, volumes and ejection fraction (EF) of all patients were re-analysed and quantified. Available data on family history, Holter findings, and electrocardiograms were also reviewed., Results: There were 5 patients (7.7%) that fulfilled major CMR criteria for ARVC: 4 were classified as having definitive ARVC; and 1/5 as borderline. There were 33 patients with no RV dyskinetic segments: none were classified as having definitive or borderline ARVC; 4/33 were classified as possible ARVC, leaving 29/33 as normal or no ARVC. Finally, there were 27 remaining patients (41.5%) with isolated RV dyskinetic segments: 1/27 was classified as definitive ARVC; 4/27 as borderline; 8/27 as possible; leaving 15/27 as indeterminate. Compared to control, those with isolated RV dyskinesia (including the subgroup labelled as indeterminate 15/27) had more abnormal RVEF, larger RV end-diastolic volume index (82 ± 12 mL/m² vs. 72 ± 12 mL/m², p-value 0.0127), and a trend for higher odds of dilated RV (odds ratio 3.0 [0.81-11], p-value 0.09)., Conclusions: Among patients with a clinical suspicion for ARVC, almost 40% had isolated focal RV dyskinetic segments with the majority remaining unclassified. This cohort had more RV dilation and abnormal EF compared to control., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2019 Korean Society of Echocardiography.)

Background: Exercise stress echocardiography (SE) is commonly used for diagnosing coronary artery disease (CAD). The use of quantitative echocardiographic measures such as strain imaging is expected to improve the sensitivity of conventional SE which relies on the visual diagnosis of wall-motion abnormalities (WMAs). This study is set to demonstrate the added value of resting and exercise strain analysis to detect underlying microangiopathy and inducible myocardial ischemia during a resting and SE in comparison with the results of coronary computed tomographic angiogram (CCTA)., Methods: A total of 103 consecutive outpatients from the executive screening program were identified and underwent resting and SE. Global longitudinal strain (GLS) and wall-motion changes at rest and peak exercise were analyzed and compared. Baseline demographics, heart rate, and blood pressure measurements were retrospectively extracted for analysis. CCTA was chosen as an alternative test to match with wall motion and strain imaging., Results: Patients who had abnormal CCTA had lower resting GLS (14.85% ± 3.05 vs 17.99% ± 2.88, P-value = .001) when compared to patients with normal CCTA. All patients who had abnormal CCTA had higher wall-motion score index (1.35 ± 0.2 vs 1.00, P-value < .0001) and lower and abnormal peak stress GLS (pGLS) as compared to patients with normal CCTA (14.89% ± 3.35 vs 18.44% ± 4.27, P-value = .007). However, all patients with pGLS ≥ 20% had normal/nonobstructive CCTA. Patients with multiple comorbidities showed reduced and lower values of resting and pGLS (P-value < .0001), suggesting associated subclinical left ventricular dysfunction., Conclusions: Global longitudinal strain offers quantitative interpretation of the resting and SE study, detects underlying subclinical left ventricular dysfunction and a peak stress value more than 20% excludes obstructive CAD on CCTA., (© 2018 Wiley Periodicals, Inc.)

A 9-year-old boy with hypereosinophilic syndrome (HES) was referred for cardiac magnetic resonance (CMR) imaging following an abnormal echocardiogram that showed a large mass layered on the inferolateral wall of the left ventricle, causing secondary severe mitral regurgitation. Cardiac involvement in HES usually affects the ventricular apex. In our case, CMR confirmed the presence of a large mural thrombus of 0.9 cm × 4.2 cm. This unusual cardiac involvement in HES was diagnosed in its intermediate thrombotic stage. CMR is very sensitive and specific in staging the disease. It explained the etiology of mitral regurgitation and guided therapy, especially when echocardiography was nonconclusive., Competing Interests: There are no conflicts of interest.

A 38-year-old healthy male presented with vomiting and profuse diarrhea, associated with blurry and yellow coloration of the vision (xanthopsia). Laboratory workup was unremarkable, except for hyperkalemia (K 5.2 mEq/L) and mildly elevated troponin level 0.11 ng/mL (cut-off value 0.08). An electrocardiogram showed sinus bradycardia with deep scooping of the T waves. Although the patient denied intake of any drugs, herbs, consumption of plants, a digoxin level was drawn and was significantly elevated >5ng/mL (therapeutic range 0.8-2.0). Further questioning revealed that the patient was a pharmacist mixing raw material to fabricate medication, and that he could have incidentally ingested contaminated water. His symptoms improved with parallel improvement in the electrocardiogram T wave abnormalities. An echocardiogram was normal. The positive troponin was felt to be secondary to severe digoxin toxicity. Review of the literature however showed no report of elevated troponin in the setting of digoxin toxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Waterpipe smoking is a rising global public health epidemic perceived by many users to be less harmful, though its toxicity overlaps or even exceeds that of cigarette smoking. Short-term cardiovascular changes due to waterpipe smoking are well established, but longer-term health impacts are still not fully elucidated., Objective: We aim to investigate the association of waterpipe smoking with myocardial infarction among patients undergoing cardiac catheterization., Methods: The study was performed on Lebanese patients referred for cardiac catheterization. Patient's blood was collected for metabolic measures and questionnaires were filled out to include socio-demographic, behavioral and pertinent medical characteristics of the study subjects., Results: Myocardial infarction is significantly and independently associated with waterpipe smoking, with odds ratio (OR) of 1.329 (95% CI: [1.04-1.68]; p = .021), which is lower than that for cigarette smoking (OR = 1.87, 95% CI: [1.63-2.15]; p < .001). Only diabetes showed significant association with waterpipe smoking among MI enrollees (OR = 1.66, 95%CI: [1.04-2.63]; p = .032)., Conclusion: The study provides yet another evidence for the adverse cardiovascular effects of waterpipe smoking on a clinical level. The harmful effects of waterpipe smoking should be underscored by health care professionals.

Background: Echocardiography has been the subject of interest in diagnosing diastolic dysfunction and estimating left ventricular filling pressures (LVFPs). The present study is set to estimate the correlation between the worsening of diastolic parameters and the evidence of inducible ischemia during an exercise stress echocardiography (SE) in comparison with the results of coronary computed tomographic angiogram (CCTA)., Methods: A total of 191 consecutive patients from the executive screening program who underwent exercise SE followed by CCTA were evaluated. Baseline demographics, heart rate, and blood pressure measurements were extracted for analysis. Standard two-dimensional and tissue Doppler imaging parameters were analyzed. Diastolic function was graded at rest and peak exercise., Results: Patients who had worsening of diastolic function by at least one grade had had 2-3-fold higher odds of having abnormal SE. In addition, patients with worsening of diastolic function had higher stress LVFPs (E/e' = 11.7 ± 2.7 vs. E/e' 8.0 ± 2.0; P < 0.0001), more E/e' change >25% (48% vs. 22%, P = 0.012), and were more likely to have obstructive coronary artery disease (CAD) on CCTA (23.8% vs. 9.2%; P = 0.045). A change in E/e' >25% (stress-rest) was highly associated with a positive stress test and abnormal CCTA result. Patients with no change or improvement in diastolic function with stress had a 92% negative predictive value of having normal SE and 91% of normal/nonobstructive CCTA., Conclusion: A worsening of diastolic function and a change in E/e' >25% (stress-rest) were associated with abnormal SE, positive stress test, and obstructive CAD when compared to CCTA results., Competing Interests: There are no conflicts of interest.

Background: Sedentary lifestyle has become prevalent in our community. Recent data showed controversy on the effect of regular exercise on left ventricular compliance and myocardial relaxation., Hypothesis: We sought to assess whether physical inactivity is an independent predictor of diastolic dysfunction in or community, after adjustment for several covariates., Methods: Consecutive outpatients presenting to the echocardiography laboratory between July 2013 and June 2014 were prospectively enrolled. Clinical variables were collected prospectively at enrollment. Patients were considered physically active if they exercised regularly ≥3× a week, ≥30 minutes each time. The primary endpoint was presence of diastolic dysfunction., Results: The final cohort included 1356 patients (mean age [SD] 52.9 [17.4] years, 51.3% female). Compared with physically active patients, the 1009 (74.4%) physically inactive patients were older, more often female, and had more comorbidities and worse diastolic function (51.3% vs 38.3%; P < 0.001). On univariate analysis, physical inactivity was associated with 70% increased odds of having diastolic dysfunction (odds ratio: 1.70, 95% confidence interval: 1.32-2.18, P < 0.001). There was significant interaction between physical activity and left ventricular mass index (LVMI; P = 0.026). On multivariate analysis, patients who were physically inactive and had LVMI ≥ median had significantly higher odds of having diastolic dysfunction (odds ratio: 2.82, 95% confidence interval: 1.58-5.05, P < 0.001)., Conclusions: In a large, prospectively enrolled cohort from a single tertiary center in the Middle East, physically inactive patients with increased LVMI had 2- to 3-fold increased odds of having diastolic dysfunction after multivariate adjustment., (© 2016 Wiley Periodicals, Inc.)

Background: More evidence is emerging on the strong association between chronic kidney disease (CKD) and cardiovascular disease. We assessed the relationship between coronary artery disease (CAD) and renal dysfunction level (RDL) in a group of Lebanese patients., Methods: A total of 1268 patients undergoing cardiac catheterization were sequentially enrolled in a multicenter cross sectional study. Angiograms were reviewed and CAD severity scores (CADSS) were determined. Estimated glomerular filtration rate (eGFR) was calculated and clinical and laboratory data were obtained. CKD was defined as eGFR < 60 ml/min. Logistic regression model was performed using multivariate analysis including all traditional risk factors associated with both diseases. ANOVA and the Tukeytestswere used to compare subgroups of patients and to assess the impact of each disease on the severity of the other., Results: Among the 82% patients who exhibited variable degrees of CAD, 20.6% had an eGFR < 60 ml/min. Logistic regression analysis revealed a bidirectional independent association between CAD and CKD with an OR = 2.01 (P < 0.01) and an OR = 1.99 (P < 0.01) for CAD and CKD frequencies, respectively. We observed a steady increase in the CADSS mean as eGFR declined and a progressive reduction in renal function with the worsening of CAD (P < 0.05). This correlation remained highly significant despite considerable inter-patient variability and was at its highest at the most advanced stages of both diseases., Conclusions: Our results show a strong, independent and graded bidirectional relationship between CAD severity and RDL. We propose to add CAD to the list of risk factors for the development and progression of CKD.

Background: The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis., Aim: The aim of this study is to investigate the effect of "selected" genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD., Methods: CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension., Results: rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137)., Conclusion: This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers.

A main underlying pathology of coronary artery disease is the deposition of cholesterol in the arteries supplying blood to the heart that leads to stenosis and myocardial infarction. We tested if dyslipidemia is a risk factor for coronary artery disease in the Lebanese population, and studied the role of the total cholesterol/HDL cholesterol (TC/HDL-C) ratio as a biological marker of coronary artery disease. We recruited 6,180 Lebanese patients undergoing cardiac catheterization. We conducted a cross-sectional association study between TC/HDL-C ratio and the number and type of vessels occluded in catheterized patients by controlling for confounding effects. The TC/HDL-C ratio ≥4 significantly predicts ≥50 % stenosis in all vessels individually with the odds ratio (OR) ranging from 1.22 to 1.92. The OR increased with increasing number of ≥50 % stenotic vessels (1.39 for 2 vessels and 1.64 for 3-4 vessels), as did risk due to diabetes, CAD family history, gender, and age. The younger than average age of onset subgroup shows a pronounced increase in risk for occlusion of the left main coronary artery due to TC/HDL-C ≥4 (OR 3.26). In conclusion, low levels of HDL-cholesterol and high levels TC/HDL-C ratio are strong biological markers of disease occurrence and severity in the Lebanese population.

The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

Extraction of cardiac implantable electrical devices (CIED) is becoming an increasing necessity. Infection is among the most frequent and serious complications associated with the surge of CIED implants. We describe the extraction of an infected cardiac resynchronization therapy-defibrillator (CRT-D) in a patient with a tunneled implantable cardioverter defibrillator (ICD) lead implanted from the right jugular vein.

Background: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease., Aims: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine., Methods: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach., Results: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia., Conclusions: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5)). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6)), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10)). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology., (© 2011 Saade et al.)

In this article, myocardial perfusion in patients with a totally occluded left anterior descending artery reinjected by a normal right coronary artery is assessed using stress single photon emission computed tomography (SPECT). In all, 20 patients, with a totally occluded left anterior descending artery reinjected by normal right coronary artery, underwent myocardial single photon emission computed tomography imaging within 60 days of angiography. All patients had abnormal perfusion single photon emission computed tomography results and 70% had reversible defects. Perfusion defects at rest were present in 75% of patients, with perinecrotic residual ischemia in 45% of patients whereas for 30% of patients, no viable myocardium was detected in the collateral-dependent segments. In all, 25% of patients had no resting perfusion defects but all are presented with stress-induced ischemia. Collaterals are not protective against stress-induced ischemia, but they can preserve myocardial viability. This conclusion is highly supported by the presence of residual ischemia in the collateral-dependent segments.

Background: Noninvasive assessment of coronary flow reserve in the left anterior descending artery (LAD) by transthoracic Doppler echocardiography (TTDE) has been already validated as a new method for determining the degree of stenosis over the proximal flow., Objectives: The aim of the study is to determine, by TTDE, the feasibility and the value of the coronary flow reserve (CFR) (defined as the maximal increase in coronary blood flow above its basal pressure for a given perfusion pressure when coronary circulation is maximally dilated) in the mid-to-distal LAD before and after percutaneous angioplasty and to demonstrate the early recovery of microvascular tone immediately after stenting., Methods: The study population consisted of 36 patients with significant isolated LAD stenosis (70-90%) identified by coronary angiography. CFR was recorded in the mid-to-distal LAD at rest and during hyperemia obtained after adenosine intravenous infusion before and after stenting., Results: Adequate visualization of the LAD was obtained in 25 out of 36 patients (70%). At rest the mean CFR was 1.5132 +/- 0.33 (1.1-2.58). However, after stenting the mean CFR was significantly higher: 2.18 +/- 0.55 (1.3-3.8), with P <0.01., Conclusions: CFR can be easily determined by TTE in approximately 70% of patients. Noninvasive Doppler echocardiography shows impaired CFR in patients with LAD disease. After stenting CFR is restored, demonstrating early recovery of microvascular tone. These results are comparable to those published in the same conditions. Larger series with a long-term follow-up may allow identifying patients at high risk for restenosis after stenting.

Detection of myocardial perfusion abnormalities using Tc-99m tetrofosmin was evaluated for sensitivity and specificity compared to coronary angiography. Between January 1996 and January 1998, exercise stress tests and myocardial scintigraphy were performed in 58 patients, followed by coronary angiography within 2 months. There were 48 males and 10 females, aged 33 to 72 years (mean, 57 years). The sensitivity and specificity of exercise stress tests were 64% and 68%, respectively, while the sensitivity and specificity of Tc-99m tetrofosmin scans were 88% and 75%, respectively, compared to angiography. For Tc-99m tetrofosmin scans, the sensitivity was 78% for the left anterior descending artery, 66% for the left circumflex artery, and 76% for the right coronary artery; specificity was 74% for the left anterior descending artery, 90% for the left circumflex artery, and 75% for the right coronary artery. It was concluded that Tc-99m tetrofosmin allowed high-quality myocardial perfusion imaging with results comparable to those obtained using thallium-201 chloride.

Ischemic cerebro-vascular events are in 15% of cases secondary to a cardiac embolus. The prevalence of echocardiographic anomalies, susceptible of being at the origin of a cerebral embolus may reach 50%. Transesophageal echocardiography (TEE) is superior to transthoracic echocardiography (TTE) in the detection of a thrombus of the left atrial appendage, spontaneous echocontrast, intra-aortic atherosclerotic plaque lesion, patent foramen ovale or an atrial septal aneurysm. The high prevalence of these anomalies in a population who presented an ischemic cerebrovascular accident does not suffice to establish a causal relationship between the anomaly and the cerebral event. Further studies seem to be necessary to establish the responsibility of these different anomalies and determine their embolic risk, by defining certain risk factors. Pending the results of such studies, TEE should be indicated more systematically in the case of an ischemic cerebrovascular accident of the young patient without a clinically evident cardiopathy, independently of the results of TTE.

The authors describe the case of a patient referred for evaluation of multiinfarct dementia. Conventional echocardiography revealed an aneurysm of the interatrial septum. A transesophageal echocardiogram demonstrated superimposed thrombus. This rare cause of systemic emboli can be diagnosed only by transesophageal echocardiography and is of major interest to avoid recurrence of ischemic strokes.

From January 1993 to January 1994, we realized at Risk Hospital 11 percutaneous mitral commissurotomies (PMC). This first Lebanese series comprised 9 women and 2 men. The mean age was 36 y (18-73 y). Ten patients were en class III of the NYHA and one in class IV (pregnant woman on the end of the 7th month). The predilatation evaluation was done by transthoracic echocardiography for the just 2 patients and by transthoracic with transesophageal multiplane echocardiography for the 9 others. The mean gradient was at 20 mmHg (10-24 mmHg) and the mean mitral area at 1 cm2 (0.65-1.5 cm2). We used the Inoue balloon for all these procedures with a stepwise technique and a color echo-doppler control between inflations. We obtain bicommissural opening in 8 patients and unicommissural opening in 3 patients. The mean gradient post dilatation was at 4 mmHg (3-8 mmHg) and the mean mitral area at 2.3 cm2 (1.5-2.8 cm2). No mitral regurgitation > 2/4 was noted. After a general review, we concluded the PMC is at present the treatment of choice of non or discrete calcified mitral stenosis and this procedure has to be taken on charge by the Ministry of Health in Lebanon.

We report two cases of coronary artery fistula discovered accidentally during coronary-angiography. One case between the left anterior descending and the pulmonary artery and another case between the circumflex and the left ventricule. Both cases were associated with hypertrophic cardiomyopathy. There was a spontaneous closure of the fistula in the first case. A brief review of the literature is presented because this anomaly is being discovered frequently because of the possibility of diagnosis with transesophageal echocardiography.

Ischemic cerebrovascular accidents are classically attributed to an embolism of cardiac origin in 15% of cases. This longstanding concept is questioned by trans-esophageal echocardiography (TEE). The incidence of anomalies which could be the origin of a cerebral embolism involves more than 50% of cases in certain series. The superiority of TEE over trans-thoracic echocardiography (TTE) emerges in particular when certain abnormalities such as an intra-atrial thrombus, spontaneous atrial contrast, an intra-aortic atherosclerotic plaque, a patent foramen ovale or an aneurysm of the inter-atrial septum are sought. The high incidence of such abnormalities in a population having sustained an ischemic cerebrovascular accident is not sufficient to establish a cause-and-effect relationship between the abnormality and the cerebral event. Certain abnormalities are commonly associated with each other or with emboligenic arrhythmias (atrial fibrillation). Studies hence remain required to determine the respective responsibilities of these various abnormalities and stratify their embolic risk by defining certain risk factors. While awaiting the result of such studies, it would seem valid to suggest the more routine use of TEE in the investigation of ischemic cerebrovascular accidents in young patients free of clinically obvious heart disease, and this regardless of the result of TTE.

A 38-year old man was admitted for investigation of suspected endocarditis presenting with two cerebrovascular accidents and pyrexia. The initial clinical, echocardiographic and infectious investigations were normal, apart from a neutrophilic leukocytosis. The clinical course was marked by the recurrence of systemic embolism in the lower limbs, the appearance of cervical and axillary lymphadenopathy and, within a short period of time, of massive aortic valve vegetations. The diagnosis of aspergillosis was made from the culture of a peripheral embolus recovered by a Fogarty catheter and this was confirmed by the positivity of serological investigations. The patient died within two months despite antifungal therapy. Aspergillus endocarditis is characterised by its rapid progression, the volume and embolic tendency of the vegetations, the relative inefficacy of medical therapy and the potential benefits of early surgical management.

The intracardiac hemodynamic responses to short periods of 70 degrees head-down and head-up tilts were studied in 12 normal male subjects, ages 19-24 years. Echo-Doppler techniques were used to measure the transmitral and transaortic flow velocities as well as cardiac index, and to evaluate the peripheral impedance. Head-down tilt (HDT) rapidly induced an increase (9.7%, p < 0.05) in the early passive filling of the left ventricle (ME peak of the transmitral flow velocity curve) and in transaortic flow velocity (8%, p < 0.05), as well as in cardiac output (6%, p < 0.05). In spite of a peripheral vasodilation, the blood pressure increased (7%, p < 0.05 for the systolic; 15%, p < 0.01 for the diastolic) and remained at a high level for the 5 min of the experiment. Head-up tilt (HUT) induced inverse responses; i.e., a large initial decrease in the transmitral (-15%, p < 0.05) and transaortic (-16%, p < 0.001) flows. The shape of the arterial peripheral flow indicated an increased vascular impedance. After a short drop, the blood pressure rapidly recovered a level statistically close to that of the pretest. In both cases, tachycardia occurred. We conclude that, in man, the cardiac responses to the changes in posture appear to be related more to the passive changes in ventricular filling due to the blood shift than to the nervous regulation by the arterial baroreflexes, whereas these reflexes mainly act in the control of the vascular impedance.

Rheumatoid valvular heart disease and aortic valve replacement for a rheumatoid lesion have been previously reported in the literature. The authors report the first case of emergency surgery for acute aortic regurgitation due to necrosis and rupture of a rheumatoid granuloma: the anatomopathological lesions observed were patholognomic.