Epicardial Adiposopathy and Atrial Fibrillation

Atrial fibrillation (AF) is the most frequent heart rhythm disorder in clinical practice. Many conditions could predispose the development of AF such as hypertension, heart failure, valvular heart disease, aging, coronary artery disease, diabetes mellitus, and sleep apnoea.

Kocyigit and colleagues reported a study to investigate the association between epicardial adipose tissue (EAT) thickness and AF recurrence after cryoballoon-based pulmonary vein isolation (PVI). A total of 249 patients (55.6 ± 10.7 years; 48.2% male; 18.5% persistent AF were followed-up for 29 months (8 months-48 months). AF after the ablation procedure was 75.9% at a median follow-up of 29 months.

Total periatrial EAT thickness (18.1 ± 6.2 vs. 14.7 ± 4.7 mm; P<0.001) was greater in patients with late AF recurrence when compared to those without. Periventricular or total EAT thickness measurements did not differ between both groups (P>0.05). Multivariate Cox proportional hazard regression analysis showed that periatrial EAT thickness (hazard ratio, 1.086; P=0.001) and left atrial volume index (hazard ratio, 1.144; P<0.001) were independent predictors for late AF recurrence. EAT thickness may serve as a beneficial parameter for prediction of AF recurrence after cryoballoonbased PVI.Read more.....

New Components of the Renin-Angiotensin-Aldosterone System and Oxidative Stress

Hypertension is a common but one of the most important health problems, because it is a major risk factor for many CVDs. So it is very important to prevent, diagnose early and treat hypertension and its complications. Renin-angiotensin-aldosterone system (RAAS) has been reported to be associated with hypertension and target organ damage for a long time. RAAS, not only in the systemic circulation but also in the local organs and tissues, has also been shown to play a crucial role in the pathogenesis ofhypertension and CVDs. And there are lots of evidences that inhibitors of ACE (ACEI) and antagonists of AngⅡ(ARBs) are effective for the treatment of hypertension and related CVDs.

Interaction of AngⅡ with its receptors, AT1 and AT2, plays the central role in the expressions of various biological functions of RAAS in kidney, heart, endothelium, brain and other tissues, However, multifunctional new components of RAAS have been identified such as various fragments of angiotensin peptides, enzymes forming these angiotensin peptides, and receptors of these peptides. These include Ang-(1-7), alamandin, Ang A, Ang-(1-12), AngⅢ, AngⅣ, and Ang- (1-9) as angiotensin peptides, and Mas (receptor for Ang-(1-7)), MrgD (receptor for alamandin), AT4/IRAP (receptor for Ang Ⅳ) (pro)renin recptor (PRR, receptor for prorenin and renin) as receptors, and ACE2 and many other enzymes.

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Wireless Monitoring of Cardiac Function

Heart failure is a huge bloom problem. The achievability of abiding ecology affection action added accurately in these patients has acquired accretion interest. The primary aim of this abstraction was to see if a wireless burden sensor can be cautiously built-in to accord authentic and reproducible abiding intracardiac burden recordings. Another aim was to see if there are any adverse furnishings affiliated with the implant. A ascendancy accumulation was included for allegory of analytic data.Forty patients with heart failure, 31 appointed for accessible affection anaplasty and 9 for transcatheter aortic valve backup (TAVR) were included to analysis the assurance and achievability of the Titan burden sensor.

Data were prospectively registered on a analytic address form, and transferred to and adored in an Excel database for approaching analysis. The abstraction architecture and sample admeasurement were called with basal action and assurance of the implant as primary endpoints. Linear corruption was acclimated to abstraction the accord amid intraoperative sensor and advertence catheter burden values. Non-parametric tests were acclimated to analysis differences amid connected variables, as the belief for course application the Shapiro-Wilks analysis was not fulfilled.

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Cell Therapy for Cardiovascular Diseases

Ischemia/reperfusion (IR) initiates various cellular and molecular changes often resulting in myocardial infarction and cardiac dysfunction. Inhibition of enzymes that are involved in cell pathology could be potential therapeutic targets especially phosphodiesterases. Pharmacological preconditioning (PC) with tadalafil, a PDE5A inhibitor enhances protein kinaseG-1 (PKG-I) activity resulting in stem cell survival and cardioprotection. PC protection has two different phases, an early (2 h) and late (24 h).

However, the mechanism of protection during these phases remained grossly unknown. Mesenchymal stem cells (MSC) from adult male Fischer-344 rats were pre-treated with tadalafil (100 μM) for an hour and subjected to 2 h of hypoxia (1% O2) followed by reoxygenation (HR: in vitro model mimicking ischemia/reperfusion). 

We observed increased MSC survival with reduced cell cytotoxicity as revealed by low LDH release and trypan blue staining respectively in tadalafil treated cells upon HR; decrease in TUNEL positivity as well as caspases activity ; an increase in pAKT/AKT, iNOS, eNOS and pGSK3β/GSK3β during early protection phase of PC. This protection seemed to be a spontaneous adaptive response of MSCs against HR and was independent of tadalafil whereas an increase in Bcl2/Bax was tadalafil dependent;  during late phase, we observed phosphorylation of STAT3 at serine727 leading to its entry inside the nucleus and binding onto the promoter of PKG-I by 3 fold (P<0.05).

Collagen Metabolism Biomarkers and Health Related Quality of Life in Pulmonary Arterial Hypertension

Objectives: The goal of this study was to investigate the association between collagen metabolism biomarkers and health related quality of life (HRQoL) in PAH patients. 

Methods: We prospectively enrolled 68 stable idiopathic, anorexigen-associated, and hereditary PAH subjects and 37 healthy controls. Serum samples were analyzed for N-terminal propeptide of type III procollagen (PIIINP), c-terminal telopeptide of collagen type I (CITP), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). The Minnesota Living with Heart Failure (MLWHF), EQ-5D (EQ-5D), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and Short Form (SF-36) general health survey were administere

d at the time of blood draw. General linear models, as well as logistic regression models were used to assess associations between variables. 

Results: CITP, PIIINP, MMP9, and TIMP1 levels, and all HRQoL domains were significantly different between controls and PAH patients (p<0.001 for each). Interestingly, PIIINP levels were significantly associated with MLWHF physical (coef=1.63, and p=0.02), SF-36 physical (coef=-2.93, p=0.004), and EQ-5D aggregate (coef=0.34, p=0.001) scores. Several of the CAMPHOR scores strongly linearly associated with PIIINP. The odds of obtaining a walk distance ≥330 meters decrease by 38% per unit increase in PIIINP (OR=0.62; 95% CI=0.43, 0.90) and a PIIINP cutoff of 5.53 μg/L provided 81% sensitivity and 82% specificity. 

Conclusions: PIIINP is the best predictor of disease severity, and is strongly related to HRQoL scores in PAH patients. These relationships suggest PIIINP as a promising tool for PAH clinicians to determine or confirm the level of disease severity.Read more......

A Novel Technique for Carotid Artery Stenting

A 74-year-old male patient was referred to our clinic for evaluation for CAS. Doppler ultrasonography (US) and magnetic resonance angiography (MRA) showed ulcerated, calcified and eccentric plaque causing 50%-60% stenosis in the proximal part of the left internal carotid artery (ICA). The patient had a history of right transient hemiparesis, which had occurred three months previously. He was on medicine for hypertension and Type 2 diabetes mellitus. Daily, 100 mg ofacetylsalicylic acid (Aspirin; Bayer healthcare, Germany) and 75 mg of clopidogrel (Plavix; Bristol-Myers Squibb/Sanofi Pharmaceuticals, NY, USA) were prescribed and the CAS was planned for approximately 10 days later. Before the procedure, Aspirin and Plavix sensitivity were tested with Verify Now (Accumetrics, San Diego, CA, USA). The patient was sensitive enough and one day later, the procedure was accomplished.

Before the procedure, a diffusion-weighted MR was performed to detect any new ischemic lesion caused by the CAS procedure. Diagnostic angiograms obtained under local anesthesia showed 50% stenosis consistent with the Doppler US and MRA. Heparin (5000 IU) was administered intravenously (IV) and then the left common carotid artery was catheterized with a long shuttle sheath (Cook Inc., Bloomington, IN, USA) with the assistance of an exchange, hydrophilic 0.035-inch guide wire; a distal protection filter (Emboshield NAV6, Abbott, Redwood City, CA, USA) was placed inside the ICA, 4-5 cm away from the stenosis. A hybrid tapered carotid stent, Cristallo Ideale 9-6×30 mm in size (Invatec, Medtronic, and Santa Rosa, CA, USA) was implanted and a 4×20 mm monorail balloon was used for dilation after stent implantation. A second, identical carotid stent, the same size as the first stent, was deployed inside the second stent for covering and preventing the plaque protrusion inside the first stent. And then, a 5×20 mm monorail balloon dilation was applied and the opening was optimal without any residual stenosis.Read more.....

Central Pseudo-Aneurysm Formation Following Arterial Closure with a StarClose SE Device

A 77-year-old man with history of ischemic cardiomyopathy with left ventricular ejection fraction 20-25% and atrial fibrillation was transferred to our hospital post cardiac arrest.He was noted to have positive troponins and was diagnosed with NSTEMI. He was treated with aspirin 81mg, a loading dose of plavix of 600 mg with subsequent maintenance dose of 75 mg and intravenous heparin infusion. After stabilization, cardiac catheterization was performed via a right femoral approach, due to limited radial arterial access, revealing multi-vessel coronary artery disease with a syntax score of 16. 

Hemostasis post-procedure was achieved with a StarClose SE device with no post deployment oozing or delayed hemostasis. He was felt to be at extreme surgical risk and was referred for highrisk percutaneous coronary intervention (PCI). Again, right femoral arterial access was obtained and a 6F sheath was introduced. PCI was performed with the placement of fourdrug-eluting stents: one in the proximal LAD, a second in the ramus intermedius, and two in the first obtuse marginal. Prior to PCI, retrograde sheath angiography was performed to evaluate the access site for hemostasis and suitability for closure.

The femoral arterial canulation site was noted to be approximately 2 cm cranial to the prior access site closed with the Star Close device (Figure 1A). Retrograde sheath angiography revealed the previously deployed Star Close clip with a 0.5 cm pseudo-aneurysm emanating from its center. As the pseudo-aneurysm was small, the decision was made to achieve hemostasis and to treat the pseudo-aneurysm simultaneously by applying manual pressure for hemostasis. There was no post-compression bleeding, oozing or other post procedure complications.Read more.....

2015 American Heart Association | American College of Cardiology

Hypertension is a major risk  factor for cardiovascular disease [1-9]. Hypertension is present in approximately 69% of patients with a first myocardial infarction. This editorial will discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension guidelines on treatment of hypertension in patients with coronary artery disease.Previous hypertension guidelines have recommended reducing the blood pressure in patients with coronary artery disease and hypertension to less than 140/90 mm Hg, to less than 130/80 mm Hg with consideration of lowering the blood pressure to less than 120/80 mm Hg if left ventricular systolic dysfunction is present to less than 140/90 mm Hg in patients younger than 80 years and the systolic blood pressure to 140-145 mm Hg if tolerated in patients aged 80 years and older, to less than 140/90 mm Hg in patients younger than 80 years and to less than 150/90 mm Hg in patients aged 80 years and older and to less than 140/90 mm Hg .

A study of 4,162 patients with acute coronary syndromes found that the lowest incidence of cardiovascular events occurred with a s blood pressure of 130-140/ 80-90 mm Hg. In a study of 8,354 coronary artery disease patients, the primary outcome of death, nonfatal myocardial infarction, or nonfatal stroke occurred in 9.36% with a systolic blood pressure (SBP) <140 mm Hg, in 12.71% with a 140-149 mm Hg SBP, and in 21.3% with a ≥ 150 mm Hg SB. Compared with a <140 mm Hg SBP, a 140 to 149 mm Hg SBP increased cardiovascular death 34%, all strokes 89%, and nonfatal stroke 70%. Compared with a SBP < 140 mm Hg, a ≥ 150 mm Hg SBP increased the primary outcome 82% , all-cause mortality 60%, cardiovascular death 218%, and all strokes 283%.

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Quality of Life in Octogenarians Undergoing Surgical Aortic Valve Replacement

Introduction:

Western societies are aging and a social policy of Western countries will be to promote quality of life (QOL) for the elderly. Consequently, quality of life assessment in the elderly should be considered when analysing the risks and benefits of any therapeutic intervention.

The European registry found that aortic valve stenosis (AS) is more frequent in subjects over 75 years , affecting up to4% of the individuals over 85 years of age .Considering that 6.9% of individuals in Asturias, Spain, are older than eighty, the health economic impact may be considerable.

Cardinal symptoms such as angina, dyspnoea and syncope, are associated with poor prognosis and once these symptoms appear, the definitive treatment is aortic valve replacement. Although some studies have demonstrated that surgical procedures in octogenarians can improvefunctional status, morbidity and mortality, thus far, few ones have investigated quality of life after aortic valve replacement .In the 1960’s, the Movement of Social Indicators of the Chicago School developed the theoretical concept of QOL. Since then, the concept has been understood in two ways: as welfare and as a vital objective associated with psychological well-being.In 1993, the World Health Organization Quality of Life (WHOQOL) group defined the term as an individual perception of life within their cultural context as well as its objectives, expectations, concerns and interests.

Right Ventricular Dysfunction in Myocardial Infarction: A New Risk Factor for Clopidogrel Resistance?

Introduction:

Right ventricular dysfunction (RVD) in acute coronary syndromes occur either primary in infarction of the right ventricle mainly caused by proximal occlusion of the right coronary artery or secondary ininfarction of the left ventricle with consecutive increase of pulmonary pressure. The incidence of right myocardial infarction has ranged w

idely according to the diagnostic technique used and the patients profile. It is recognizable clinically in two thirds of hypotensive inferior infarction and most inferior infarctions with cardiogenic shock. 

The recommended treatment in acute myocardial infarction is percutaneous coronary intervention (PCI) with stent deployment in order to restore myocardial perfusion . Dual inhibition of platelet aggregation with a thienopyridine like clopidogrel andaspirin showed a dramatic reduction of major adverse cardiac events after PCI .In the past years there have been several studies that showed the importance of sufficient response to clopidogrel to prevent thrombembolic complications. 

Furthermore, different studies showed the importance of an early detection of clopidogrel resistance as it is associated with worse outcome after PCI .

Since clopidogrel is a prodrug, which has to be metabolized into the active metabolite by two Cytochrome P-450 dependent steps in the liver, the inter individual variability for the responsiveness to clopidogrel is high. Especially in hemodynamically unstable patients with cardiogenic shock and multi organ dysfunction resorption and metabolization of clopidogrel may not be ensured.

Proper Analysis of Categorical Outcomes: Make Sure You Understand the Model

Introduction: This letter is written in response to the recent publication by Darabont et al. regarding the possible relationship between Acute Pulmonary Edema (APE) and Renal Artery Stenosis (RAS). In this publication, the authors used a statistical technique known as “linear discriminant analysis” to assess the relationships between selected predictor variables (including APE) and their study outcome (RAS). Although the authors are commended for taking on this investigation, the choice of statistical analysis is inappropriate for their data, and has some technical assumptions which make it unsuitable for the manner in which it was used by Darabont et al.

Briefly, linear discriminant analysis is meant to find a linear combination of factors that correctly predict or characterize a certain event. This may sound like technical jargon, but simply put it is a way to predict a categorical outcome variable using continuous predictor variables. To the statistically fluent reader, this may sound a lot like logistic regression, and it should; logistic regression, also, essentially creates a model using a linear combination of factors to predict a categorical outcome variable. However, there are key technical differences between the two, and there is a reason that logistic regression remains highly prevalent today while linear discriminant analysis is rarely seen.In 1978, Press and Wilson compared lineardiscriminant analysis to logistic regression and found that logistic regression was the superior technique in the vast majority of cases. 

The Role of NLRP3 Inflammasome in Cardiovascular Diseases

Introduction:

NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome is a cytosolic protein complex involved in the pathogenesis of atherosclerosis . After the endothelial NLRP3 inflammasome is activated by intracellular cholesterol crystals, it directly produces endothelial dysfunction and may initiate or exacerbate vascular injuryduring hypercholesterolemia. In addition, an assembled inflammasome promotes the maturation and release of proinflammatory cytokines interleukin-1β (IL-1 β) and IL-18 .

IL-1β and IL-18 act as mediators that promote the cascade release of other cytokines. These interleukins have been previously implicated in the pathogenesis of atherosclerosis . 

Wang et al found that NLRP3 and downstream cytokines are correlated with the severity of coronary artery disease (CAD).The NLRP3 inflammasome is up-regulated within the myocardium after myocardial infarction(MI), primarily in non-cardiomyocytes (i.e. fibroblasts). Its deficiency markedly improves myocardial function and reduces infarct size after ex vivo myocardial ischaemia–reperfusion (I/R) injury. It was Sandanger  who suggested that the NLRP3 inflammasome is up-regulated in myocardial fibroblasts after MI, potentially contributing to infarct size after myocardial I/R.

Cardiac Analysis of Autologous Transplantation of Cocultured Skeletal Myoblasts and Mesenchymal Cells in a Rat Model Doxorubicin-Induced Cardiotoxicity: Histopathological and Functional Studies

Introduction:

Cancer affects more than 1.6 million of Americans and is believed to be the second most common cause of death (after accidents, injuries and intoxication) in children. Unfortunately, cardiotoxicity is the most severe of chronic complications of antineoplastic therapy. Doxorubicin (DOX) is an anthracycline effective antitumor agent used in cancer treatment and the most widely used and successful chemotherapeutic for childhood cancers. However, its clinical use is limited due to its severe and irreversible cardiotoxicity including the development of cardiomyopathy, and ultimately congestive heart failure .

The significant advances in therapeutic modalities, such as heart or ventricular transplantation, have emerged in the field of regenerative medicine with the use of mesenchymal stem cells (MSCs). During the past decade, it has been demonstrated that MSCs possess outstanding potential for cardiac regeneration based on their multipotential differentiation ability, easy tissue accessibility and capacity for ex-vivo expansion.

Transplantation of satellite cell-derived myoblasts has therapeutic potential for repairing damaged heart and has been used both, experimentally and clinically, in an attempt to restore cardiac function. Therefore, transplantation of cocultured cells remains an attractive approach for myocardial repair.

So, the current study was conducted to evaluate the functional and histopathological effect of combined transplantation of MSCs and SM in doxorubicin-induced cardiomyopathy.

Heart Ware HVAD use as Bridge to Transplantation by using Berlin Heart EXCOR Support

Continuous-flow ventricular abetment accessories are getting built-in with added abundance in the United States in accouchement with end-stage affection failure. We address the aboriginal appear use of the HeartWare HVAD in an 8 year old boy who had a history of biventricular abutment with BerlinAffection EXCOR accessories 4 years previously. He was accurate on the HeartWare for 198 canicule above-mentioned to accepting a affection transplantation. The implantable HeartWare HVAD can be acclimated to accommodate circulatory abutment for those who accept had antecedent paracorporeal automated circulatory support.

Dilated cardiomyopathy (DCM) is the final date of assorted genetic, metabolic, and acquired altitude that affects the cardiac myocyte. For abounding accouchement with DCM, affection transplantation (HT) is the lot of acknowledged and continued abiding therapy. As an arch to HT, mechancal circulatory abutment (MCS), and accurately ventricular abetment accessory (VAD) analysis is getting acclimated with added abundance in adults and children. Ventricular abetment accessory analysis potentially restores end-organ function, facilitates rehabilitation, and improves accommodating antagonism for HT.

A 4 year old Hispanic macho with DCM and end date affection abortion accessory to atomic myocarditis underwent acknowledged article of biventricular Berlin Affection EXCOR accessories afterwards a 14 day stabilization aeon on extra-corporeal film oxygenation (ECMO). The accommodating was maintained on biventricular abutment with closing cogent accretion of biventricular action and explantation of the accessories on post-operative day (POD) 15.

To date, this case represents the aboriginal acknowledged use of Hearware HVAD as an arch to transplantation in an accommodating with a history of antecedent article with biventricular Berlin Affection EXCOR devices. While medical analysis is acceptable for some patients with affection failure, there is a growing pediatric citizenry who crave HT who accept been bridged to transplantation with assorted forms of MCS. Accordingly, they appear use of VAD analysis has added badly in the pediatric citizenry in the accomplished 10 years.

Early Aortic Root and Left Main Coronary Artery Thrombosis after Left Ventricular Assist Device Implantation

Introduction:

In the modern era, the use of surgically implanted left ventricular assist devices (LVADs) as a bridge therapy to either recovery or cardiac transplantation has given a hope at the end of the HF course of disease. More recently, the use of LVADs as “DT” has further illuminated a future for patients with end-stage HF.

Today, LVADs have evolved from large, bulky pulsatile systems to smaller, compact, fully implantable continuous flow (CF) pumps. These CF-LVADs use rotodynamic pumps to transfer kinetic energy from a circulating impeller to the bloodstream, thereby generating forward flow .

Starling et al. summarized the rate of device thrombosis among 837 patients across three implantation centers in USA, and Kirklin et al. described data reported to the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) on the rate of device thrombosis among 6910 patients from 2011 till April 2014. But all these big studies were done on Heart Mate2 devices (Thoratec) and very few were done on (HeartWare) HVAD devices.

Left main coronary artery thrombosis and aortic root thrombosis are rarely described, but in our case; thrombus had occurred earlywith the newer generation (HeartWare) HVAD device despite full anticoagulation and antithrombotic coverage.

Case Report:

39 years old man was diagnosed with severe dilated cardiomyopathy since 2003 with recurrent admissions due to decompensated congestive heart failure. Dual Chamber ICD was inserted in 2012, but removed after few months due to infection and thrombosis. He is a known diabetic on insulin therapy, heavy smoker with liver cardiac cirrhosis and has severe chronic kidney disease with baseline creatinine around 200 mmol/L. Echocardiography showed severe LV dysfunction with EF less than 20% and RV moderate to severe dysfunction with systolic PAP pressure 55-65 mmHg.

Comparison of Clinical Outcomes among Patients Undergoing Coronary Artery Bypass Grafting (CABG) with or without Prior Percutaneous Coronary Intervention (PCI)

Introduction:

Percutaneous coronary intervention (PCI) is emerging as the main treatment option for coronary artery disease and the number of PCI procedures are rapidly increasing worldwide .

Today, coronary artery bypass grafting is very commonly performed in patients who have recurrent symptoms after previously successful PCI either because of late failure of the deployed PCI or more commonly because of progression of the native disease. The widespread use of PCI has resulted in an increasing number of patients being referred for CABG surgery who have undergone prior PCI .

While the efficacy and outcomes for PCI and coronary artery bypass grafting as the primary treatment for coronary disease are well documented, there is little recent data available that specifically focuses on those patients who ultimately receive a surgical graft after a supposedly initially successful PCI .

There are a number of hypotheses as to whyprevious PCI may adversely affect outcomes with CABG

Another reason can be compromise of left ventricular function and loss of collateral circulation due to occlusion of side branches especially when many stents are deployed. Distal micro-embolization from stents is another possible cause of left ventricular dysfunction. Endothelial dysfunction induced by stenting is well known. Furthermore, the necessity to bypass the coronary artery more distally where it is smaller with more diffuse disease especially in patients with multiple stents can also be a cause of worse outcomes after CABG.

Tako-Tsubo Stress Cardiomyopathy-A Quantum Event of the Heart?

Tako-tsubo cardiomyopathy, named for a Japanese fisherman’s octopus trap, is an extraordinary event wherein a so-called stress event induces a large area of myocardial stunning. Tako-tsubo cardiomyopathy was first described in Japan by Dr. Sato at the Hiroshima City Hospital in 1990. In its classic form, there is aneurysmal dysfunction of the apical myocardium with dyskinesis and bulging of the ventricular wall, but with preserved function of the base of the heart. As might be predicted, there are also other atypical variants, including one, which is reported to affect selectively the midportion of the left ventricle. Tako-tsubo’s cardiomyopathy is now considered to represent a group of acute onset cardiomyopathies, which are also named stress-induced cardiomyopathies.

We would like to open a discussion around the prevailing opinions and the available evidence that this cardiomyopathy is the result of an adrenaline surge, with stress causing microvascular dysfunction on a wide scale. Atherosclerotic plaque rupture or erosion with in situ thrombosis resulting in ST elevation myocardial infarction (STEMI or acute heart attack) has been considered a distinct event, unrelated to Tako-tsubo cardiomyopathy. 

However, many of the measurements demonstrating a catecholamine excess and abnormal  vasoreactivity, signs of microvascular dysfunction, have been recorded after the inciting event is complete. Thus, only a snapshot of the devastation is seen. Just as when a photographer captures the after effects of a tidal wave, the initial seismic event that results in a tsunami is not recorded.

We would like to suggest that plaque erosion and thrombosis with distal emboli causing downstream or distal microvascular occlusions may be, like a tidal wave that wreaks havoc on the shoreline, the initiating events for a cardiomyopathy such as Tako-tsubo. It is certainly well understood that the coagulation serine protease system, the inflammatory and also the hemodynamic vascular systems that regulate arterial pressure and tone have very close interactions. This editorial is intended to open up a discussion on the potential inciting events for this cardiomyopathy.

Positive Response to Cardiac Resynchronization Therapy - The Role of NT-proBNP

Cardiac resynchronization therapy (CRT) became available in the late 1990s, offering a safe and effective treatment for patients suffering from heart failure with left ventricular systolic dysfunction (LVEF<35%) and electrical dyssynchrony (QRS duration ≥ 120 ms) . However, positive clinical response is observed in only 60- 70% of the treated population, and significant echocardiographic remodeling is observed in 50-60% of the treated population . The reasons for “non-response” seem to be multifactorial, while different studies have used different definitions of echocardiographic and clinical factors to indicate positive response . Using different criteria for response in different studies makes it difficult to make head-to-head comparison of outcome and results as different subpopulations of “responders” may be examined, and there may thus be different implications for clinical outcomes.

 Additional data from biochemical markers such as NT-proBNP carries a prognostic value in CRT patients, and postoperative reduction has been shown to correlate to reduced long-term mortality . Monitoring NTproBNP may therefore help more easily identify primarily the nonresponders for early intervention and more intensive care with a view to improving their quality of life and clinical outcome. Our study sought to compare baseline NT-proBNP levels in relation to clinical and echocardiographic positive response to CRT, and also to assess the association between the extent of change in NT-proBNP levels with echocardiographic and/or clinical response.

Association among Systolic Blood Pressure Variation, Inflammation and Arterial Rigidity in Essential Hypertension

Introduction:

Although the association among arterial rigidity, inflammation and atherosclerosis has been established, that among systolic blood pressure variability (BPV, defined as blood pressure variation per unit time, inflammation and arterial rigidity is yet to be elucidated. The present study, which is the first to report simultaneous measurements of BPV (assessed by coefficient of variation (CV) in ambulatory blood pressure monitoring (ABPM)), inflammation (as reflected by levels of high-sensitivity C-reactive protein (hs-CRP) and arterial rigidity (assessed by brachial-ankle pulse wave velocity (ba-PWV) at baseline and 1-year follow-up, is aimed at testing the hypothesis that greater blood pressure variation (which is higher among hypertensive than normotensive individuals translates into stronger shearing force on the arterial wall, which could trigger inflammation (known to be involved in the pathogenesis and progression of hypertension  leading to arterial rigidity. The target of antihypertensive therapy therefore would not only be good blood pressure control and improved endothelial function but also BPV lowering with consequent decreased inflammation and greater arterial elasticity. The present study was conducted in Northeast China, where essential hypertension, which is associated with increased mortality, is common and daily salt intake is relatively high, approximately 16-18g, increasing susceptibility to atherosclerosis and more severe cardiovascular diseases.

Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects

Introduction:

Several studies have reported the antioxidant, anti-inflammatory, anticancer, hypocholesterolemic and neuroprotective properties of tocotrienols in different cell lines, animal models, and in humans . However, question on the bioavailability of pure tocotrienols remained unanswered. Therefore, it is important to understand the absorption and bioavailability mechanism of tocotrienols before carrying out investigations into the therapeutic efficacy in humans. The bioavailability of naturally-occurring tocotrienols differ considerably in their absorption, therfore therapeutic uses of tocotrienols remain controversial. It was reported that after feeding rats mixed tocotrienols, the oral bioavailability of α-tocotrienol was 28% compared to 9% of γ-tocotrienol and δ-tocotrienol. Tocotrienols in humans were detected in postprandial plasma , and they were found enriched in triacylglycerol-rich particles, HDL, and LDL after administration of palm tocotrienol-rich fraction (mixture of 68% tocotrienol + 32% α-tocopherol). The key parameter of bioavailability determination, the total area under the concentration-time curve (AUC0 - ∞, h) for plasma α-tocotrienol, was 60% larger than for γ-tocotrieno.

It was also reported that the bio-discrimination of α-tocopherol (vitamin E) influences the rate of tocotrienol absorption, due to high affinity of α-tocopherol with “α-tocopherol transfer protein” (α-TTP), which mediates secretion of α-tocopherol (100%) from the liver into the circulatory system, and is much higher than α-tocotrienol (12%) or other tocotrienols. Moreover, α-tocopherol has been reported to attenuate the cholesterol-lowering effect of tocotrienols through activation of the HMG-CoA reductase activity (whereas tocotrienols have a desirable inhibiting effect on its activity). Also α-tocopherol interferences with tocotrienol functions such as attenuation of cancer inhibition , exacerbation of stroke injury, inhibition of absorption, and induction of tocotrienol catabolism. 

Fetal Anomaly Screening for Detection of Congenital Heart Defects

Congenital heart defect (CHD) is defined as defect in the heart and major blood vessels, including structural, chromosomal, genetic, biochemical defects and malformations. CHD is the most common congenital malformation in live births with an incidence of around 1% in general population. The incidence of critical CHD (needing intervention or operation within 1 month after birth) is around 2 per 1000. CHDs remain a leading cause of infant mortality accounting for up to 40% of all deaths from congenital defects. Up to 7.5% of the infant mortality in the developed world is reported from CHDs.

Major developments in diagnosis and management over the last decade have led to dramatic improvements in survival with more than 85% of children diagnosed with CHD now surviving into adulthood. Early diagnosis and timely appropriate management of critical and serious CHDs is essential to improve outcome.

Current screening tests are fetal anomaly screening (FAS) and routine examination of newborn. Pulse oximetry screening has been shown an effective screening method to detect critical CHDs and fulfils the criteria for universal screening. It’s being recommended by most professional bodies involved in the care of children with CHDs and currently being adopted by many countries across the world. However, it’s still not part of universal screening programme in most of the countries.

Routine examination of newborn remains a poor screening tool to detect CHDs soon after birth when cyanosis could be difficult to detect with naked eyes and clinical signs of CHDS are often absent. Fetal anomaly screening has now become an established screening tool to detect CHDs in most of the developed countries. 

Now, the International Society for Ultrasound in Obstetrics and Gynaecology (ISUOG), Royal College of Obstetrics and Gynaecology (RCOG) and National Institute of Clinical Excellence (NICE) guidelines all recommend both four-chamber and outflow tract views of the heart as part of FAS  (https://www.gov.uk/ government/publications/fetal-anomaly-screening-programme-standards). This increases the probability of identifying CHDs involving abnormalities of the outflow tracts (including transposition of the great arteries [TGA], tetralogy of Fallot, and double outlet right ventricle [DORV]). A significant improvement in the antenatal detection rate of significant CHD can be achieved when a concerted effort is made to visualise the outflow tracts .

Difficulty in Diagnosis of Leiomyosarcoma of Infrahepatic Inferior Vena Cava

Introduction

Leiomyosarcomas of the inferior vena cava are rare malignant and slow-growing tumors with a poor prognosis. It was first reported by Perl and Virchow in 1871, in the German literature. There were approximately 400 documented cases in the literature, which were originated from the smooth muscle cells of the media and predominantly proposed within the IVC. Resection was often presented with a challenge as these tumors may require reconstruction of the inferior vena cava (IVC). These papers reported on a case of surgical resection of an infrahepatic IVC leiomyosarcoma mimicking a hepatic tumor with IVC tumor thrombus.

Case Report

A 61-year-old woman was detected as her right upper abdominal in pain. Laboratory findings included that the total bilirubin of 3.8 mol/L, albumin 39.3 g/L, alanine aminotransferase (ALT) 46 IU/L, aspartate aminotransferase (AST) 98 IU/L, and alkaline phosphatase (ALP) 65 IU/L. She was HBsAg (-), HBV-DNA (-). Her alpha-fetoprotein (AFP), carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9 (CA199) were all within the normal range. The functional status of the liver was assessed as Child A. Enhanced computed tomography of the abdomen revealed a tumor and was detected in the Spiegel of the liver with 7×6×5 cm mass. Areas of hemorrhage and necrosis may be noted within the mass on CT. Magnetic resonance imaging (MRI) of this tumor revealed a contrasting that low intensity on the T1-weighted image and high intensity on the T2-weighted image and extending from the left caudate lobe to IVC. We diagnosed this tumor is a hepatic tumor in the Spiegel lobe with IVC tumor thrombus.

A right subcostal laparotomy with upper midline extension to the xiphoid process was performed. A laparotomy was performed and intraoperative findings revealed a 7 cm×6 cm×5 cm hard- tumor involving the suprahepatic IVC. This tumor was not located in the Spiegel lobe of the liver but originated in the IVC. The falciform ligament was divided until the anterior surface of the suprahepatic IVC was exposed, and the infrahepatic IVC was dissected and mobilized. The tumor and the right renal vein was reached and exposed. In order to exposing the infrahepatic IVC lengthen, the left lateral section of liver was resected. The tumor was then dissected and removed from proximal to distal. After completed mobilization of tumor with adjacent pancreas, en bloc resection of the IVC tumor was performed under THVE (first Pringle’s maneuver, then the infrahepatic IVC occlusion with a Satinsky clamp, and last, suprahepatic IVC occlusion with a Satinsky clamp). The primary IVC wall was repaired longitudinally; and the relaxation was on the contrary. That was maintained for 10 minutes for the stage of enable resection. Intraoperative blood loss was 800 ml

Expression of Oncodrivers HER-3 and C-MET during Breast Tumorigenesis in BRCA Mutation Carriers

BRCA1 and BRCA2 germ line mutations confer a substantial risk of breast cancer, with studies reporting an average cumulative risk of breast cancer by age 70 years as 57-65% in BRCA1-mutation carriers 45-47% in BRCA2-mutation carriers . Today, the prevention of breast cancer among mutation carriers has focused on surgical options such as risk-reducing bilateral mastectomy and bilateral salpingooophorectomy  which have significant associated morbidity. In the general population chemoprevention strategies have been developed to target the known phenotypes of spontaneous DCIS in order to prevent the development of invasive breast cancer. As such, evaluation of the pre-invasive progression pathways of BRCA-associated tumors is critical in the effort to develop directed prevention therapies for this vulnerable population.

Prior studies have demonstrated the morphological and immunohistochemical differences between BRCA-associated and sporadic invasive breast cancers, specifically with regards to the low expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor in BRCA1-associated breast cancers . While much is known about the phenotypic differences between BRCA-associated and sporadic breast invasive cancers, there is a paucity of data about the differences in their pre-invasive progression pathways. Furthermore, because more BRCA-related breast cancers are discovered between screening mammograms and with no prior pathologic findings it has previously been thought that the DCIS-associated premalignant pathway that exists in sporadic breast cancers is not present within the BRCA-associated disease spectrum.

 In our recent original article “DCIS in BRCA1 and BRCA2 Mutation Carriers: Prevalence, Phenotype, and Expression of Oncodrivers C-MET and HER3”, we examined 114 tumor specimens from BRCA mutation carriers who underwent breast surgery at a single academic institution over a 20-year time period. We found that 80.2% of all BRCA-associated invasive breast cancer (IBC) specimens had ductal carcinoma in situ (DCIS) present, and this did not differ by mutation status (p=0.95). We found that the majority of BRCA-associated DCIS was high grade (BRCA1: 68.9%, BRCA2: 53.6%) and the DCIS was either intermixed with the IBC (BRCA1: 42.9%, BRCA2: 56.0%) or just on the periphery of the IBC (BRCA1: 50.0%, BRCA2: 44.0%). In BRCA1 mutation carriers with IBC and concurrent DCIS, the correlation between the DCIS and IBC was highly significant for ER, PR, HER1, HER3, and C-MET (p<0.01). In BRCA2 mutation carriers with IBC and concurrent DCIS, the correlation between the DCIS and IBC was highly significant for ER, PR, HER2, and HER3 (p<0.01). Most BRCA1-associated DCIS and IBC had 0/3 staining intensity for ER, PR and HER2, while most BRCA2-associated DCIS and IBC had 3/3 staining intensity for ER and PR. BRCA1-associated DCIS had higher expression of HER3 and CMET (H-Score 99.5 and 101.9, respectively) and lower expression of HER1 (H-Score 6.5). BRCA-2 associated DCIS similarly had higher expression of HER3 and C-MET (H-Score 84.3 and 124.8, respectively) and lower expression of HER1 (H-Score 16.5).

Spontaneous Remission in Congenital Leukemia AML-M1 with Pericardial Effusion

Introduction

As fetal scanning is key to the diagnosis of various congenital anomalies, prenatal ultrasound is widely used in obstetrical practice in Japan. We encountered recently a pregnant woman with atypically enlarged and clear double-bubble in the fetal abdomen. This case indicated that differential diagnoses should include a rare anomaly of double atresia occurring in the esophagus and proximal jejunum in fetuses with double-bubble sign.

Case Report

A 28-year-old nulliparous Japanese woman presented with doublebubble sign in the fetal abdomen and polyhydramnios on ultrasound study at gestational week (GW) 25. Atypically enlarged and clear double-bubble with enlarged distal portion of the esophagus on MRI study at GW 27 in the fetus suggested double atresia of the esophagus and duodenum in this patient (Figure 1). Chromosomal analysis using amniotic fluid obtained at amnioreduction at GW 33 for treatment of polyhydramnios revealed normal male karyotype. An otherwise healthy infant was born vaginally at GW 36 weighing 2794 g, but required tracheal intubation because of insufficient respiration caused by the abdominal distension. He was diagnosed as having double atresia, including jejunal atresia 3 cm distal to the ligament of Treitz and esophageal atresia. The distance between the esophageal pouches was less than 1 cm and there was no tracheoesophageal fistula (TEF). These were surgically repaired at 1 and 36 days of age, respectively. The patient left hospital at 69 days of age with an uneventful postoperative course.

Discussion

To our knowledge, there have been no reports on double atresia involving the esophagus and jejunum showing double-bubble sign. The double-bubble sign, originally described on plain radiography, but now also appreciable on ultrasound and MRI, is a result of excessive fluidfilled structures in the abdomen. Therefore, double-bubble sign is seen prenatally in fetuses with various alimentary tract pathologies . Although the most frequent pathology for the double-bubble sign is duodenal stenosis/atresia , it is not exclusively pathognomonic for duodenal atresia. Pathologies other than duodenal stenosis/atresia presenting with a double-bubble sign include cystic biliary atresia, colonic duplication, malrotation with midgut volvulus, and triple gut atresia.

Comparison of the Onset of Action and Behavioral Responses to Intranasal and Sublingual Routes of Midazolam Sedation in Children - A Randomized Controlled Trial

Young children with serious oral illnesses and non complianceoften test the patience and skills of the Pediatric dentists.Children aged 3 to 7 years with severe pain and pathology aremore anxious and have difficulty in communicating properlyto the dentist . Pain and the treatment procedures assuch influencethe behavior of the children in the dental office.These children require local anesthetic drug administration to alleviate the pain. The reaction of the child to local anesthetic drug administration can be a sign of emerging perception which further affects the behavior of the children in the dental office. Pharmacologic behavior management might be needed to manage them. Moderate sedation as described by American Academy of Pediatric Dentistry (AAPD) refers to drug induced depression of consciousness during which patients respond purposefully to verbal commands. Transmucosal sedation has gained a lot of importance in pediatric dentistry in the last decade. The term transmucosal means “through, or across a mucous membrane”. Transmucosal drug delivery system includes drugs administration through rectal, intranasal and sublingual routes. These routes offer a rapid onset and bypass  first pass metabolism. Being non invasive, these routes can be child friendly. Among the medications available, midazolam has gained a lot of attention as a good pediatric sedative

agent in the recent years. It is a short acting benzodiazepine with rapid onset, faster recovery, anxiolytic and anterograde amnestic effects. The rapid onset of midazolam makes it an ideal sedative agent to be used in dental office as a sedative agent. Recent studies have shown that intranasal and buccal routes have also been used as alternative routes for midazolam administration. There

is limited literature in the use of sublingual midazolam sedation in pediatric dentistry. Hence this study was planned to assess the onset of action and behavior of the children after intranasal and sublingual midazolam sedation.

A randomized controlled trial was planned and the study protocol was approved by the Institutional Review Board, KSR Institution of Dental Science and Research, (KSRIDSR) Tiruchengode, Tamil Nadu. Ethical clearance was obtained. The study followed the principles for medical research involving human subjects described by Helsinki declaration. Sample size was calculated based on the work of Shashikran et al. with type I error 5% and power of test 80% and it was calculated to be 36. Hence 48 apprehensive children who reported to the Department of Pedodontics and Preventive dentistry, KSRIDSR during the study period (August 2013 to August 2014) and who needed treatment under sedation were selected for the study. 

Environmental Impact Assessment of Petrochemical Industry using Fuzzy Rapid Impact Assessment Matrix

Introduction

Modern petroleum engineers have used many equations to describe the physics behind the fluid flow through porous media. Under ideal situations these equations, which form the basis of modern software, yield accurate results. However, ever so often engineers are faced with challenging problems that seemingly defy physics: be it a well test problem, a history matched simulation model, or even a tool as simple as the material balance. Upon further investigation, engineers have to concede to the simple explanation that the assumptions behind those equations were violated. Even further discomforting is the admission that engineers have not yet properly characterized the physics behind the fluid flow through porous media.

Darcy’s pioneering work is at the heart of all equations related to porous media. Often engineers use it without question. Forchheimer  demonstrated the departure from linearity for high velocity flows. However little has been said about the validity of Darcy Law at low velocities. Considerable amount of work  has already been published in this area outside of petroleum, but it has not seeped through the petroleum engineering literature.

Darcy’s law

Darcy’s Law is based on the experimental observation that the apparent fluid velocity is proportional to the applied pressure gradient on a porous medium. This observation is analogous to flow of fluid through pipes, capillaries (Poisseuille’s Law) and also to that of flow of current through a resistive conductor. Wyckoff, separated Darcy’s original constant of proportionality into permeability (a property of the porous medium) and viscosity (a property of the fluid.

Following sections discuss some of the well-known departures from Darcy’s Law.

Post Darcy flow effect: Forchheimer made observations that the Darcy’s Law deviated from linearity for high velocities. He attributed this to the inertial losses. He proposed a velocity squared term to account for this non-linearity. Even in 1901, Forchheimer noted that some experimental data does not fit his newly proposed quadratic flow equation. He then proposed the addition of a cubic term to describe those data. Due to the less than proportional increase in flow velocity with respect to applied pressure gradient, this effect has shown a significant influence on well performance . This effect is generally termed as Non-Darcy flow; however in this study we will refer to it as Post-Darcy flow. Later studies [8-10] have published the impact of Post-Darcy flow on fractured gas wells. The literature already has effectively dealt with Post-Darcy flow and the reader is suggested to consult elsewhere for a more comprehensive treatment of the subject.