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1.  Long-term Outcome after Percutaneous Coronary Intervention Compared with Minimally Invasive Coronary Artery Bypass Surgery in the Elderly 
Elderly patients with unstable coronary artery disease (CAD) have better outcomes with coronary revascularization than conservative treatment. With the improvement in percutaneous coronary intervention (PCI) techniques using drug eluting-stents, this became an attractive option in elderly. Minimally invasive coronary artery bypass grafting (MICS-CABG) is a safe and effective alternative to conventional CABG. We aimed to explore the long-term outcomes after PCI vs MICS-CABG in ≥75 year-old patients with severe CAD.
A total of 1454 elderly patients (≥75 year-old patients) underwent coronary artery revascularization between January 2005 and December 2009. Patients were selected in the study if they have one of the Class-I indications for CABG. Groups were divided according to the type of procedure, PCI or MICS-CABG, and 5 year follow-up.
Among 175 elderly patients, 109 underwent PCI and 66 had MICS-CABG. There was no significant difference observed in both groups with long-term all-cause mortality (31 PCI vs 21% MICS-CABG, p=0.151) and the overall 5 year survival was similar on Kaplan-Meier curve (Log rank p=0.318). The average length of stay in hospital was significantly shorter in the PCI than in the MICS-CABG group (4.3 vs 7.8 days, p<0.001). Only 4.7% of the PCI group were discharged to rehabilitation facility compared with 43.9% of the MICS-CABG group (p<0.001). The rate of repeat revascularization was significantly higher in the PCI group than in the MICS-CABG group (15 vs 3%, p=0.014).
Among elderly patients, long-term all-cause mortality is similar after PCI and MICS-CABG. However, there is a significantly higher rate of repeat revascularization after PCI.
PMCID: PMC4780507  PMID: 27014373
Coronary artery disease; Elderly; MICS-CABG; PCI
2.  Pseudomonas aeruginosa Infective Endocarditis Following Aortic Valve Implantation: A Note of Caution 
Transcatheter aortic valve implantation (TAVI) is an alternative treatment for severe aortic valve stenosis (AS) in patients with prohibitive risk for surgical aortic valve replacement (SAVR). Prosthetic valve endocarditis (PVE) is a rare complication of this relatively novel procedure and current guidelines do not include specific recommendations for its treatment.
We report a case of PVE due to Pseudomonas aeruginosa after TAVI that required SAVR, with successful outcome.
PVE usually occurs during the first year after TAVI and entails a high mortality risk because patients eligible for this min-imally invasive procedure are fragile (i.e. advanced age and/or severe comorbidities). Additionally, clinical presentation may be atypical or subtle and transesophageal echocardiogram (TEE) may not be conclusive, which delays diagnosis and treatment worsening the prognosis. This case highlights that open SAVR might be ultimately indicated as part of treatment for TAVI-PVE despite a high-risk surgery score.
PMCID: PMC4780508  PMID: 27014375
Infective endocarditis; prosthetic valve endocarditis; Pseudomonas aeruginosa; TAVI; TAVI associated endocarditis; transcatheter aortic valve implantation
3.  High-altitude Pulmonary Hypertension: an Update on Disease Pathogenesis and Management 
High-altitude pulmonary hypertension (HAPH) affects individuals residing at altitudes of 2,500 meters and higher. Numerous pathogenic variables play a role in disease inception and progression and include low oxygen concentration in inspired air, vasculopathy, and metabolic abnormalities. Since HAPH affects only some people living at high altitude genetic factors play a significant role in its pathogenesis.
The clinical presentation of HAPH is nonspecific and includes fatigue, shortness of breath, cognitive deficits, cough, and in advanced cases hepatosplenomegaly and overt right-sided heart failure. A thorough history is important and should include a search for additional risk factors for lung disease and pulmonary hypertension (PH) such as smoking, indoor air pollution, left-sided cardiac disease and sleep disordered breathing. Twelve-lead electrocardiogram, chest X-ray and echocardiography can be used as screening tools. A definitive diagnosis should be made with right-sided heart catheterization using a modified mean pulmonary artery pressure of at least 30 mm Hg, differing from the 25 mm Hg used for other types of PH.
Treatment of HAPH includes descent to a lower altitude whenever possible, oxygen therapy and the use of medications such as endothelin receptor antagonists, phosphodiesterase 5 blockers, fasudil and acetazolamide. Some recent evidence suggests that iron supplementation may also be beneficial. However, it is important to note that the scientific literature lacks long-term randomized controlled data on the pharmacologic treatment of HAPH. Thus, an individualized approach to treatment and informing the patients regarding the benefits and risks of the selected treatment regimen are essential.
PMCID: PMC4780514  PMID: 27014374
Altitude physiology; cardiac failure; epidemiology; treatment
4.  Testosterone and Cardiovascular Disease 
Cardiovascular disease [CVD] is a leading cause of mortality accounting for a global incidence of over 31%. Atherosclerosis is the primary pathophysiology underpinning most types of CVD. Historically, modifiable and non-modifiable risk factors were suggested to precipitate CVD. Recently, epidemiological studies have identified emerging risk factors including hypotestosteronaemia, which have been associated with CVD. Previously considered in the realms of reproductive biology, testosterone is now believed to play a critical role in the cardiovascular system in health and disease. The actions of testosterone as they relate to the cardiac vasculature and its implication in cardiovascular pathology is reviewed.
PMCID: PMC4780522  PMID: 27014372
Atherosclerosis; Cardiovascular disease; Hypogonadism; Testosterone; Vascular biology
5.  Correlations Between Cardiovascular Autonomic Control Indices During the Two-hour Immobilization Test in Healthy Subjects 
The aim of the present study was to assess the features of dynamics of cardiovascular autonomic indices and correlations between them during the two-hour immobilization test in healthy subjects.
Photoplethysmogram (PPG) and electrocardiogram were recorded simultaneously during the two-hour immobilization test in 14 healthy subjects (5 men and 9 women) aged 29±5 years (mean±SD). Dynamics of heart rate variability (HRV) power spectrum in high-frequency and low-frequency ranges (in ms2 and percents of total spectral power), mean heart rate (HR), and index S of synchronization between 0.1-Hz rhythms in PPG and HR were analyzed.
Individual dynamics of all studied cardiovascular autonomic indices during the two-hour immobilization test was unique in each healthy subject. Two groups of healthy subjects were identified basing on individual features of autonomic control. The group with initial low level of index S maintained the low level of S during the two-hour immobilization test. The group with initial high index S maintained the high level of S only during the first 100 minutes of test. During the last 20 minutes of test, index S was similar in both groups. Many cardiovascular autonomic indices correlate between themselves for an individual subject, but they do not correlate between the subjects. Multiple regression analysis in each subject has shown a high correlation between mean HR and all other studied autonomic parameters in 57% of subjects (multiple R>0.9, P<0.05). For 204 records analyzed without taking into account the individual features of subjects, the above mentioned correlation was smaller (multiple R=0.45, P<0.001). Index S was found out to be the most independent one among the autonomic indices.
Cardiovascular autonomic control is characterized by a pronounced variability among healthy subjects and stability in time in each subject. We have not found any regularity in variation of cardiovascular autonomic indices, which is common for the entire group of healthy subjects during the two-hour immobilization test. Mean HR is a summary index of efficiency of heart autonomic control. Index S is the most independent cardiovascular autonomic parameter.
PMCID: PMC4797682  PMID: 27053965
0.1-Hz oscillations; autonomic control; cardiovascular system; heart rate variability; healthy subjects; immobilization test; photoplethysmogram; synchronization
6.  A Peculiar Case of a Floating Angio-Seal 
To show a complication of the use of an Angio-Seal™ closure device.
We present a patient with a systolic murmur in his femoral artery after PCI. The murmur was caused by a dislocated Angio-Seal™, a vascular closure device. This was diagnosed by Doppler Ultrasound. The device was surgically removed.
Vascular complications, such as lower limb ischemia, requiring surgical intervention tend to be higher after use of a vascular closure device. We advise routine physical examination of the puncture site after percutaneous closure with a vascular closure device, such as an Angio-Seal™. The removal of the device can be performed via an open or endoscopic approach, based on available experience.
PMCID: PMC4797688  PMID: 27053966
Angio-Seal; complication; ischaemia; vascular closure device
7.  Evidence for an Association Between Tako-Tsubo Cardiomyopathy and Bronchial Asthma: Retrospective Analysis in a Primary Care Hospital 
We investigated the prevalence of bronchial asthma in patients with Tako-Tsubo Syndrome (TTS).
This retrospective case-series study was conducted in a primary care hospital in Zurich, Switzerland. Data of all patients with newly diagnosed TTS (2002 - 2012) were assessed electronically by the use of ICD-10. Asthma prevalence was compared to published epidemiologic data.
Bronchial asthma is characterized by airway inflammation and, during attack, release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of treatment for asthma patients. Likewise, catecholamine mediated diffuse microvascular myocardial dysfunction seems to be of critical importance for the development of TTS.
20 cases of TTS were identified. 90% were female, showed a median age of 70±13y [25y - 90y], an apical and/or midventricular ballooning pattern with preserved basal function and a median initial LVEF of 34±9% [25% - 55%]. 65% of patients underwent coronary angiography to rule out significant coronary artery disease. Hypertension was present in 45% of patients, 35% were smokers, none was suffering from diabetes. Prevalence of asthma in patients with TTS was significantly higher compared to the normal population (25% vs. 7%, p=0.012). In 30% of the TTS patients an iatrogenic cause for development of TTS was identified.
Prevalence of asthma was significantly higher in patients with TTS compared to epidemiologic data from an age-matched population. Phenotypes of patients developing obstructive ventilatory disease and TTS might share common pathogenic mechanisms beyond the use of bronchodilatators. In addition, we identified other iatrogenic etiologies in patients with TTS.
PMCID: PMC4353125  PMID: 25767631
Bronchial asthma; sympathomimetic drugs; Tako-Tsubo-Syndrome
8.  Body Surface Mapping of T-wave Alternans Depends on the Distribution of Myocardial Scarring 
T-Wave alternans (TWA) testing using 12-lead electrocardiogram/Frank leads is emerging as an important non-invasive biomarker to identify patients at high risk of Sudden Cardiac Death (SCD). Cardiac scarring is very common among cardiomyopathy patients; however, its influence on the body surface distribution of TWA has not yet been defined. Our objective was to perform a simulation study in order to determine whether cardiac scarring affects the distribution of TWA on thorax such that the standard leads fail to detect TWA in some of cardiomyopathy patients; thereby producing a false-negative test. Developing such a novel lead configuration could improve TWA quantification and potentially optimize electrocardiogram (ECG) lead configuration and risk stratification of SCD in cardiomyopathy patients. The simulation was performed in a 1500-node heart model using ECGSIM. TWA was mimicked by simulating action potential duration alternans in the ventricles. Cardiac scarring with different sizes were simulated by manipulating the apparent velocity, transmembrane potential and transition zone at varied locations along the left ventricular posterior wall. Our simulation study showed that the location of maximum TWA depends on the location and size of the myocardium scarring in patients with cardiomyopathy, which can give rise to false-negative TWA signal detection using standard clinical leads. The TWA amplitude generally increased with the increment of scar size (P<0.00001). We found one specific location (a non-standard lead) that consistently appeared as the top five maximum TWA leads and could be considered as an additional lead to improve the outcome of the TWA testing in cardiomyopathy patients.
PMCID: PMC4378024  PMID: 25834653
Body surface mapping; cardiomy-opathy; ECGSIM; sudden cardiac death; t-wave alternans testing
9.  Cardiovascular Risk Assessment and Effects on Behavior in Switzerland The Swiss Heart Foundation HerzCheck®/Cardio-Test® 
“CardioTest®” is a tool for cardiovascular risk assessment. The aim of this study was to evaluate if this test used in Swiss pharmacies provides risk stratification and if it had impact on individual behaviour.
Individuals were evaluated (blood pressure, body waist circumference, random blood samples and coronary artery disease risk factors). The cardiovascular risk was calculated (AGLA Risk Score (ARS) a modified PROCAM Score) and participants were informed about their result. One year after the initial testing individuals were followed up by questionnaire with respect to the action they had taken based upon the ARS results. The relation between ARS results and events during follow-up were assessed. Events were defined as cardiovascular events due to chest pain, myocardial infarction or stroke.
A total of 1415 individuals were contacted for follow-up, 746 (53%) with a mean age of 62.7 (±12.8) years (60% were male) returned their questionnaire. The cardiovascular risk throughout the study-population turned out to be low: 73.9% had a low ARS <10%, 21.7% an intermediate ARS 10-20% and 4.4% had a high ARS >20%. Significantly more participants with ARS >20% consulted their family doctor (46.2%) than those with ARS 10-20% (25.2%) and ARS <10% (10.4%), respectively (p<0,01 for both comparisons). Sixty-four individuals (9%) suffered a cardiovascular event. The event rates increased as a function of ARS.
The overall cardiovascular risk of individuals participating in a pharmacy based risk assessment program seems to be low. CardioTest ® provided risk stratification with respect to future cardio-vascular events. CardioTest ® seems to have impact on individual behavior and lifestyle modification. Other settings and locations for screening might be considered to reach higher risk individuals at an earlier stage.
PMCID: PMC4378025  PMID: 25834654
Coronary artery disease; risk factors; risk assessment; lifestyle
10.  Association of High Blood Pressure with Body Mass Index, Smoking and Physical Activity in Healthy Young Adults 
The purpose of this study was to examine the associations between resting blood pressure (BP), smoking, physical activity (PA) and body mass index (BMI) in Greek young adults.
Materials and Methodology:
A standardised questionnaire and the Greek version of IPAQ-short were given to 1500 randomly selected health science students, in order to record smoking behaviour, PA status, BMI and resting BP. All healthy young adults aged 19-30 years old were eligible. The final size of the study cohort was 1249 students (522 men).
Males’ BP was 129.2/77.0 mmHg, significantly higher than the females’ values of 119.9/73.4 mmHg. Approximately 17% of the total population were classified as overweight and 3% as obese. In the overall population, smoking prevalence was 35.2%, with 15.3% being heavy smokers (≥21 cigs/d). Smoking prevalence did not differ significantly between sexes. The prevalence of health-enhancing PA (high PAclass) was only 14.0%, while 42.8% of the study population were classified as insufficiently active (low PAclass). Of the three lifestyle risk factors examined, only BMI was significantly and directly associated with systolic and diastolic BP levels. The prevalence of hypertension (≥140/90 mmHg) was significantly higher in men compared to women, and in obese and overweight participants compared to normal-weight subjects. Smoking and categorical PA (PAclass) were not correlated with BP. Continuous vigorous PAscore was significantly and directly associated with systolic BP, but only in males.
BMI was significantly and directly associated with resting BP in both sexes. Smoking prevalence and PA status were not associated with BP in this sample of Greek young adults.
PMCID: PMC4378027  PMID: 25834651
Blood pressure; body mass index; obesity; physical activity; risk factors; smoking
11.  Local Use of Ankaferd Blood Clotter in Emergent Beating Heart Coronary Artery Bypass Grafting 
Severe beeding which requiring massive blood transfusion after emergent beating heart surgery is shown to be 1–3%. Therefore, complications and side effects of transfusion can be seen. The aim of this study was to investigate the effectiveness of Ankaferd blood clotter (ABC) as a new topical herbal blood clotter to decrease mediastinal bleeding in emergent beating heart CABG patients who medicated with clopidogrel and acetyl salisilic acite (ASA) prior to CABG surgery.
Materials and Methods:
25 CABG patients received a high dose clopidogrel (600 mgr) and 300 mgr ASA have been included into the study (ABC group). 25 patients have also been included into the study for comparison (placebo group, PG). After the administration of protamine sulphate, a 10 ml of ABC solution has been sprayed to the surgical area including mediastinum and epicardial sac. We compared mediastinal drenaige, reoperation due to tamponade, and required blood and blood products in both groups.
The mean amount of bleeding after operation was 230 ml in ABC group, and 490 ml in CG (P=0.001). In ICU, bleeding in ABC group and CG was 410ml and 680ml, respectively (P=0.0022). The mean total bleeding from mediastinum was 530±280 mL and 990±440 mL In ABC and CG group, respectively (P=0.001). The amount of autotransfusion was as follows: 175 mL in ABC group, and 290 mL in CG (P=0.002). No patient needed the surgical revision in ABC group, but four patients (16%) from CG group because of cardiac tamponade. Seventeen patients from CG required blood transfusion due to low hematocrite level postoperatively. In CG, the mean hematocrite level was 17±2,3. Transfusion of fresh frozen plasma and platelets in ABC group and CG were as follows: 0.2 and 0 in ABC group, and 0.3and 0.4 in CG.
Our study showed that the local use of 10 mL ABC reduces bleeding significantly. Therefore, transfusion requirements of PRBC, platelets, and total blood units in patients on clopidogrel and ASA undergoing emergent beating heart CABG. To provide cardiac tamponade because of excessive mediastinal bleeding and requirement of blood transfusion after emergent CABG patients who previously administered clopidogrel and ASA, we propose local use of ABC solution as a potent coagulant agent.
PMCID: PMC4378067  PMID: 25834652
Ankaferd blood clotter; haemostasis; beating heart CABG
12.  Is Vitamin D Deficiency a New Risk Factor for Cardiovascular Disease? 
The role of vitamin D in the regulation of bone metabolism has been well established. However, in recent years, many studies have demonstrated that its role extends far beyond bone health. Growing evidence has shown a strong association between vitamin D deficiency and hypertension, metabolic syndrome, diabetes mellitus and atherosclerosis. The mechanisms by which vitamin D exerts its cardiovascular protective effects are still not completely understood, but there is evidence that it participates in the regulation of renin-angiotensin system and the mechanisms of insulin sensitivity and activity of inflammatory cytokines, besides its direct cardiovascular actions. In this review, several studies linking vitamin D deficiency with cardiometabolic risk as well as small randomized trials that have evaluated the cardiovascular effects of its supplementation are presented. However, large randomized placebo-controlled studies are still needed before we can definitively establish the role of vitamin D supplementation in the prevention and control of cardiovascular disease.
PMCID: PMC4391213  PMID: 25866591
Atherosclerosis; Cardiometabolic risk; Cardiovascular disease; Risk factor; Supplementation; Vitamin D deficiency
13.  Effect of Change in VO2max on Daily Total Energy Expenditure in a Cohort of Norwegian Men: A Randomized Pilot Study 
To investigate how a change in VO2max induced through 6 weeks of high intensity aerobic interval training affects daily total energy expenditure (TEE), active energy expenditure (AEE) and mitochondrial function in people not previously exposed to structured high intensity aerobic interval training (AIT).
Thirty healthy males (39±6 yrs) not exposed to structured exercise training were randomized to either 1x4 min AIT (1-AIT), 4x4 min AIT (4-AIT), both at 90-95% maximum heart rate (HRmax) or 47 min of MCT at 70% HRmax. TEE, AEE, number of steps, active time, sedentary time, VO2max and mitochondrial function in m. vastus lateralis were measured before and after intervention.
TEE increased 14% (p=0.014) and AEE increased 43% (p= 0.004) after MCT. There was no change in TEE or AEE after 1-AIT or 4-AIT, but 1-AIT had significantly lower TEE (p=0.033) and step-count (p=0.011) compared to MCT post intervention. VO2max increased 7% after 1-AIT (p= 0.004) and 9% after 4-AIT (p=0.004), with no change after MCT. No change was observed in maximal mitochondrial respiration (VMAX) or Citrate Synthase (CS) activity within or between interventions. Basal respiration (V0) increased after 1-AIT (p=0.029) and 4-AIT (p=0.022), with no significant change after MCT.
AIT interventions that increase VO2max, do not stimulate subjects to increase TEE or AEE. The intensity of exercise seems to play apart, as MCT increased TEE and AEE and AIT did not. Emphasis should be placed on the importance of maintaining everyday activities when introducing structured exercise training to untrained individuals.
PMCID: PMC4421836  PMID: 25969700
high intensity training; VO2max; daily energy expenditure; mitochondria
14.  Evaluation of Glycemia Control Achieved by Glargine and Lispro Versus Detemir and Aspart Insulin Regimes in Type 2 Diabetics Undergoing Surgery 
There is paucity of scientific literature regarding the clinical outcome of long lasting basal insulin and rapid acting mealtime insulin regimes in surgical situations although employed in non-surgical situations. This study has evaluated the clinical outcome of two subcutaneous split-mixed Glargine+Lispro and Detemir+Aspart insulin regimes in type 2 diabetics undergoing surgery.
PMCID: PMC4541298  PMID: 26312079
Aspart; Detemir; Glargine; Lispro; Surgery; Type 2 DM patients
15.  Blunt Thoracic Aortic Injuries: New Perspectives in Management 
Blunt thoracic aortic injuries (BTAIs) present a great challenge because of their potentially fatal outcomes. Recent advancements in their management have proved to be beneficial in terms of various parameters, including mortality and complications. Endovascular repair is now the treatment of choice in most centres and is continuously replacing the traditional open surgical method. We present a mini-review of the most recent relevant literature that briefly describes the major shifts in the diagnosis and treatment of BTAIs and compares the outcomes of the conventional surgical approach to those of the endovascular method for the definitive repair of these injuries. Although both the reviewed literature and the most recently published guidelines are in support of the use of the endovascular approach, as short and midterm results are promising, its long-term outcomes still remain in question.
PMCID: PMC4541313  PMID: 26312081
Blunt thoracic aortic injury; cardiovascular surgery; endovascular repair; delayed repair; open repair; trauma
16.  Effects of Bileaflet Mechanical Mitral Valve Rotational Orientation on Left Ventricular Flow Conditions 
We studied left ventricular flow patterns for a range of rotational orientations of a bileaflet mechanical heart valve (MHV) implanted in the mitral position of an elastic model of a beating left ventricle (LV). The valve was rotated through 3 angular positions (0, 45, and 90 degrees) about the LV long axis. Ultrasound scans of the elastic LV were obtained in four apical 2-dimensional (2D) imaging projections, each with 45 degrees of separation. Particle imaging velocimetry was performed during the diastolic period to quantify the in-plane velocity field obtained by computer tracking of diluted microbubbles in the acquired ultrasound projections. The resulting velocity field, vorticity, and shear stresses were statistically significantly altered by angular positioning of the mechanical valve, although the results did not show any specific trend with the valve angular position and were highly dependent on the orientation of the imaging plane with respect to the valve. We conclude that bileaflet MHV orientation influences hemodynamics of LV filling. However, determination of ‘optimal’ valve orientation cannot be made without measurement techniques that account for the highly 3-dimensional (3D) intraventricular flow.
PMCID: PMC4541318  PMID: 26312080
Diastolic filling; left heart model; left ventricular hemodynamics; mechanical heart valve; particle imaging velocimetry; shear stress; vorticity
17.  Long-term Effect of Optimized Sedation and Pain Management after Sudden Cardiac Arrest 
Background and Aims:
Appropriate use of sedatives and analgesics is essential to keep critically ill patients comfortable and to prevent prolonged mechanical ventilation time and length of stay in ICU. Aim of this study was to analyse the long-term effect of an algorithm-based individual analgesic-sedative protocol on mechanical ventilation time and ICU length of stay in critically ill patients after sudden cardiac arrest due to ST-elevated myocardial infarction.
Subject and Methods:
We examined a total of 109 patients before and after implementation of an algorithm-based sedation management. Our sedation protocol included individual defined sedation goals achieved by standardized sedation strategies. Mechanical ventilation time and ICU length of stay were analysed for three groups of patients: before and after the intervention and in the long-term follow-up.
We observed shorter median mechanical ventilation time and ICU length of stay in the interventional and longterm follow-up group compared to the standard-care group without statistical significance.
Our results demonstrate a long-term reduction of mechanical ventilation time and ICU length of stay achieved by implementation of an individual sedation management. This suggests sedation guidelines as effective tools to reduce the mechanical ventilation time and ICU length of stay in patients after sudden cardiac arrest in ST-elevated myocardial infarction. Investigations with a larger patient number and higher statistical power are required to confirm these findings.
PMCID: PMC4645869  PMID: 26664658
Sedation protocol; long-term effect; guideline; mechanical ventilation.
18.  6th Hellenic Congress in Athens, of the Hellenic Atherosclerosis Society, on the 04-06 December 2014 Novel Pharmacologic Treatments of Familial Hypercholesterolaemia 
Familial hypercholesterolaemia (FH) is the most common inherited monogenic lipid disorder. It is caused by mutations of genes related to low density lipoprotein (LDL) receptors, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 (PCSK9). Homozygous FH (HoFH; 1/400,000 births) is treated by LDL apheresis. Recently lomitapide has been used for the treatment of HoFH as a monotherapy or in addition to LDL apheresis. Heterozygous FH (HeFH), 1/250-1/200 births, is associated with an increased cardiovascular disease (CVD) risk. The main treatment for HeFH has been high doses of high intensity statins plus ezetimibe. However, this is not usually enough to attain LDL-C targets, especially in those with overt CVD or equivalents (LDL-C goal of<70 mg/dl). Data from the Atherosclerosis Risk in Communities study showed that loss of function mutations of PCSK9 were associated with a 28% lower LDL-C level and an 88% reduction in the risk of CVD in blacks, while in whites these numbers were 15% and 47%, respectively. This led to the development of technology to block PCSK9 with monoclonal human antibodies (e.g. evolocumab and alirocumab). These antibodies have been shown in phase II and III trials to be safe and to produce reductions in LDL-C levels by around 60% either as monotherapy or on top of optimal therapy with statins and ezetimibe. These antibodies are administered subcutaneously every 2 weeks with an automatic device. Anti-PCSK9 antibodies are expected to be licensed soon (? in 2015) and are considered by many as “the statins of the 21st century”.
PMCID: PMC4645966  PMID: 26664657
19.  Impact of Magnesium L-Lactate on Occurrence of Ventricular Arrhythmias in Patients with Implantable Cardioverter Defibrillators: A Randomized, Placebo-Controlled Trial 
We evaluated the antiarrhythmic efficacy and quality of life (QoL) impact of oral magnesium Llactate on patients with an implantable cardioverter defibrillator (ICD).
This prospective, double-blind, placebo-controlled trial randomized 70 patients with an ICD to receive oral magnesium L-lactate 3 tablets twice daily (504mg elemental magnesium daily) or matching placebo for 12 months. Patients were seen at baseline, 12, 24, 36, and 52 weeks. The primary endpoints were the cumulative occurrence of ICD therapy [either shock or anti-tachycardia pacing (ATP)] or QoL between the groups.
Among the 70 randomized patients with a mean ± SD follow-up of 6.4 ± 4.1 months, 10 patients in the placebo group and 8 in the magnesium group experienced either ICD shock or ATP [HR 0.84, 95% CI 0.33 to 2.12; p=0.706]. Without significant arrhythmia suppression, only minimal effects on QoL were seen. Eighty six percent of all patients had serum intracellular magnesium deficiency.
In our underpowered trial, patients with ICDs had intracellular magnesium deficiency but oral magnesium Llactate only nonsignificantly reduced the occurrence of ICD therapies and had little impact on HrQoL.
PMCID: PMC4768635  PMID: 27006710
Magnesium; implantable cardioverter defibrillator; arrhythmia; quality of life
20.  Oxidative Damage in the Aging Heart: an Experimental Rat Model 
Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults.
PMCID: PMC4768636  PMID: 27006709
Aging; Catalase; Glutathione; Lipid Peroxidation; Protein Carbonylation; Rat; ROS; Superoxide Dismutase.
21.  Stent Thrombosis after Rescue Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction 
Main Problem:
To determine the incidence of coronary stent thrombosis (ST) in patients with acute ST segment elevation myocardial infarction (STEMI) after rescue percutaneous coronary intervention (PCI).
An observational study looking at the incidence of ST in a middle-eastern population. A total of 510 consecutive patients presented with ST-segment elevation myocardial infarction (STEMI) were enrolled and underwent thrombolytic therapy with a total follow-up period of 2 years. Study outcomes were ST, death, re-infarction or acute coronary syndrome requiring coronary angiography and PCI.
A total of 510 patients enrolled, all diagnosed with STEMI and underwent thrombolytic therapy. Only 100 subjects underwent rescue PCI with intra-coronary stenting, including 54 patients with drug-eluting stent (DES) and 46 patients with bare metal stent (BMS). During the study period and follow-up, the overall rate of ST was 13.7%, definite ST occurred in 6 patients (5.5%), probable ST in 8 patients (7.3%), and possible ST in one patient (0.9%), including 0.9% acute ST, 0.9% sub-acute ST, 2.8% late ST and 8.3% very late ST. Patients with ST were likely to have prior PCI (p=0.001), prior coronary artery bypass grafting (CABG) (p=0.002) and history of heart failure (p=0.04).
ST is infrequent event with major consequences in patients presenting with STEMI in the first 2 years after stent implantation.
PMCID: PMC4768653  PMID: 27006716
Acute myocardial Infarction; Arab; Bahrain; Gulf States; Middle East; Stent Thrombosis; STEMI.
22.  Successful Direct Adsorption of Lipoproteins (DALI) Apheresis During Pregnancy in an Omani Woman with Homozygous Familial Hypercholesterolemia 
We report our experience with Direct Adsorption of Lipoproteins (DALI) apheresis in an Omani pregnant woman affected by homozygous familial hypercholesterolemia. To the best of our knowledge this is the first successful pregnancy treated with DALI apheresis.
The patient had a history of coronary artery disease, supra-aortic valvular stenosis and severe carotid artery disease with right carotid artery stenting. She was on a regular biweekly DALI apheresis since 2008. In May 2013, she became pregnant and rosuvastatin and ezetimibe were stopped while she continued on DALI apheresis biweekly. This treatment during pregnancy was successful with no major complications. The average low-density lipoprotein cholesterol reduction during therapy was 50%. She spontaneously delivered a healthy male infant (2,400 g) at 37 weeks. We showed that DALI apheresis therapy was safe during pregnancy with a good outcome for both mother and neonate.
PMCID: PMC4768655  PMID: 27006714
Familial hypercholesterolemia; low density lipoprotein receptor; xanthoma; LDL-apheresis; pregnancy
23.  Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment 
Background and Aim:
Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels.
Materials and Methods:
Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use.
At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 μg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001).
In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy.
PMCID: PMC4768659  PMID: 27006717
Continuous positive airway pressure; hypoxia; insulin-like growth factor binding protein-3; obstructive sleep apnea; vascular endothelial growth factor; treatment.
24.  Angiotensinogen (AGT) M235T, AGT T174M and Angiotensin-1-Converting Enzyme (ACE) I/D Gene Polymorphisms in Essential Hypertension: Effects on Ramipril Efficacy 
Hypertension, one of the most important risk factors for premature cardiovascular disease, is a major worldwide public health problem. Angiotensin-1-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms are thought to be associated with primary hypertension. In the present study, we examined the frequency of these gene polymorphisms in an adult population with and without essential hypertension. Furthermore, we evaluated the effect of ACE and AGT gene polymorphisms on ramipril treatment efficacy in the hypertensive patients.
A total of 166 adults (83 hypertensives and 83 normotensives) were involved in the study and genotyped for AGTM235T (rs699), AGTT174M (rs4762) and ACEI/D (rs1799752) gene polymorphisms.
The genotype and allele distribution of the AGTM235T variant significantly differed between hypertensives and normotensives [odds ratio (OR) = 1.57% (T vs M allele), 95% confidence intervals (CIs): 1.01 - 2.44; p=0.045 for hypertensives]. However, none of the 3 studied Simple Nucleotide Polymorphisms were associated with the blood pressure-lowering response to ramipril.
These results suggest that AGTM235T gene polymorphism is associated with essential hypertension. However, none of the AGTM235T, AGTT174M and ACEI/D gene polymorphisms influenced ramipril effectiveness.
PMCID: PMC4768660  PMID: 27006715
AGTM235T; AGTT174; ACEI/D gene polymorphisms; efficacy; hypertension; ramipril.
25.  Outcomes of Primary Percutaneous Coronary Intervention for Patients with Previous Coronary Artery Bypass Grafting Presenting with STsegment Elevation Myocardial Infarction 
There are limited data on outcomes of patients with previous coronary artery bypass grafting (CABG) presenting acutely as ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI).
To compare outcomes in STEMI patients undergoing PPCI with or without previous CABG surgery.
An all-comer single-centre observational registry from a cardiothoracic centre in UK. All consecutive patients presenting for PPCI between 2007 and 2012 were included. Electronic records were used to extract relevant information. Mortality data were obtained from the Office of National Statistics. Overall median follow-up period was 1.7 years (intraquartile range 0.9-2.5).
Complete data were available for 2133 (97%) patients. 47-patients had previous history of CABG. Out of these, the infarct related artery (IRA) was native vessel in 22 and graft in 25 patients. Post re-vascularization TIMI flow was inferior in CABG cohort (
Patients presenting with STEMI to PPCI service with history of CABG are less likely to achieve acute reperfusion and have worse angiographic outcomes. Post PPCI, the prior CABG patients do not seem to have worse shortterm and long-term prognosis.
PMCID: PMC4768661  PMID: 27006712
Acute myocardial infarction/STEMI; coronary bypass grafts; Primary PCI.

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