Potential markers for Coronary artery diseases

The incidence of Coronary artery disease (CAD) is mainly caused due to endothelial dysfunction or atherosclerosis and can be found in both developing and developed countries. Recent studies have shown that high homo cysteine levels are significantly associated with the CAD. Even low levels of vitamins like B12 and folic acid are associated with CAD. 

Despite best efforts, available therapies protect only 30-40% of individuals at risk, and no therapeutic cure is anticipated for those who currently suffer from the disease. The endothelium is a single layer of cells lining all blood vessels. It plays an important role in many physiological functions, including the control of blood cell trafficking, vasomotor tone, vessel permeability, and hemostatic balance. Endothelial cells produce a wide variety of substances in response to various physical and chemical stimuli, including vasodilator substances, and vasoconstrictor substances. Read more..............

Twelve Month Follow-Up Audit of Nigerian Hypertensives on Back Titration

The question of whether pharmacotherapy for systemic arterial hypertension should be life-long has continued to agitate the mind of care givers and patients alike. Whereas it is possible in some cases to reduce dose or discontinue drug(s) outright, relapse of high blood pressure is known to occur after some time. All the same, the attitude of step down or outright discontinuation of anti-hypertensive pharmacotherapy appears to be safe provided close monitoringcontinued. 

In an audit of hypertension care in a specialized care facility, the author observed that some patients remained controlled despite self-imposed drug holidays or physician initiated dose reduction following therapy induced hypotensive features. Some earlier workers had called for future studies to shed light on how long and intensively hypertensives could be treated before discontinuation of therapy can be embarked upon. Read more...................

Endofibrosis in an Endurance Athlete

A 35-year-old endurance athlete was referred for unexplained claudication-like complaints in his left lower limb. Elsewhere he was treated for functional compartment syndrome and operated for poplitealartery entrapment syndrome which proved unsuccessful. 

He complained of a painful and swollen left thigh at maximal exercise. Clinical investigation, ankle-to-brachial indices at rest and an additional magnetic resonance angiography were normal. 

An incremental treadmill test showed pathological ankle-to-brachial pressure measurement, duplex ultrasound imaging confirmed flow limitation and showed lesions of endofibrosis in the left external iliac artery. Surgery consisted of performing an endarterectomy of the external iliac artery with venous patching. Read more.................

What is Ventricular Tachycardia for an Automated External Defibrillator?

The present algorithm for the treatment of cardiac arrest relies on the paramount difference as to whether the underlying rhythm is shockable or not. Accordingly, only two options exist namely a rhythm in a cardiac arrest patient can be either shockable or not shockable. This exemplification was introduced in the 2000 Guidelines for Cardiac Arrest and Cardio Pulmonary Resuscitation (CPR) that overcame the previous classification which considered four main types of rhythms (asystole, pulseless electrical activity - PEA-, ventricular fibrillation and pulseless ventricular tachycardia) . The last two are those requiring prompt defibrillation.

Since then, this simplified algorithm became a standardized scheme which allowed a more schematic approach. For the treatment of ventricular tachycardia it is apparent that this rhythm may undergo an electrical defibrillation only in presence of a pulseless condition which cannot be detected by any kind of defibrillator. Indeed ventricular tachycardia may need prompt defibrillation in case of pulseless rhythms but may require synchronized electrical cardioversion when the patient is hemodynamically unstable but is not in cardiac arrest.  Read more.................

ACE Inhibitors or Sartans in the Treatment of Hypertension: A Needless Discussion?

Most patients who suffer from essential arterial hypertension must be treated with a antihypertensive preparation in order to adequately control blood pressure. According to current ESH (European Society of Hypertension)/ESC (European Society of Cardiology) guidelines, physician have at their disposal five main groups of antihypertensives (as also referred to as basic antihypertensives) for use in either monotherapy or in combination: diuretics, beta-blockers (BB), calcium ion channel blockers (CaI), angiotensin convertase (ACE) inhibitors and sartans.

Basic antihypertensives possess very similar efficacies in terms of blood pressure reduction. When used at full dose, the average drop of systolic blood pressure(SBP) is 9.1 mm Hg and diastolic blood pressure (DBP) 5.5 mm Hg. However, before the initiation of pharmacotherapy, other co-morbidities , contraindications and other factors must be taken into consideration. Considering the guidelines, initiation with renin-angiotensin-aldosterone system (RAAS) inhibitors i.e. ACE inhibitors or sartans is mostly recommended for a majority of co-morbidities. Alpha-1 blockers should only be considered in resistant hypertension, if no contraindication exists. Methyldopa (an alpha-2 agonist) should be preferred in hypertensive pregnant women. Read more............

Renal Denervation, ?Last Resort? or Alternative Therapy?

Arterial hypertension represents one of the main causes of morbidity and mortality among the population with high risk of cerebral strokes, coronary heart disease.It’sarbitrarily defined as “resistant” or “refractory” when recommended blood pressure targets are not achieved, despite changes in lifestyle and treatment with adequate doses of at least three antihypertensive drugs from different classes, including a diuretic.

In a recent clinical study, it’s proved a variable proportion (approximately 5-15%) of the general population of the patients with hypertension in treatment, which refer to the Centres of Excellence for the diagnosis and treatment hypertension, may be considered suffering from resistant hypertension. It‘s evident that 5-15% of patients with hypertension, Whereas 20% of the Western population is suffering from hypertension, is easy to understand the true dimension of the phenomenon. So the choice of treatment, comes to a crossroad. Should we insist with the combination of more than three medications, or choose the path of renal denervation? Read more...............

A NEW CCD IMAGING TECHNIQUE TO ASSESS CONTRACTILITY AND FUNCTIONING OF HEART

The ex vivo heart perfusion model is a well-accepted preparation, introduced more than a century ago. Nowadays, it is not so much used in the study of heart’s physiological principles, but in supplying corresponding physiological evidence to underlying molecular processes of ischemia, altered myocardial metabolism, new pharmaceutical agents, etc.,

Although it was named after Oscar Langendorff who demonstrated its use in the mammalian heart in 1895, the same model was well established by Elias Cyon in the frog heart as early as 1866 . The chronological reference tothe origin of the method is important not only for historical referencereasons, but also, and particularly so, for highlighting the tremendous efforts of the early physiologists to develop suitable recording methods in parallel. Although the continuous pressure monitoring was achieved quite early, almost simultaneously with the genesis of the model, the morphometric assessment of the beating heart, by means of volumetric changes, diastolic and systolic changes, was not possible until much later, during Starling’s era. Read more.............

  

Ruptured Abdominal Aortic Aneurysm in A Patient with A Retroaortic Left Renal Vein

The surgical management of Abdominal Aortic Aneurysms (AAAs) is well established, and the most challenging intraoperative complication of this procedure is venous bleeding. A Retroaortic Left Renal Vein (RLRV) is an infrequent anomaly, with a reported incidence of 1.8 to 2.4% . An RLRV is sometimes overlooked on the preoperative images, because surgeons are focused on evaluating the AAA. However, the presence of an RLRV makes it difficult to clamp the proximal neckof the AAA without injuring the venous structures. Injury to an RLRV may resultin life-threatening bleeding. Therefore, accurate preoperative diagnosis of venous anomalies is an important aspect of minimizing the risks associated with abdominal aortic surgery. We report a case of ruptured AAA associated with an RLRV, in which accurate preoperative diagnosis was obtained by evaluation of contrast-enhanced Computed Tomography (CT) images.

Case Report:  An 84-year-old woman was referred to our hospital by ambulance because of severe lumbar pain. She was diagnosed with AAA at another hospital before. She was conscious and alert at admission with a blood pressure of 112/60 mmHg and a heart rate of 72 beats/min. Her hemoglobin level was 7.4 g/dL, serum creatinine level was 1.66 mg/dL, and estimated glomerular filtration rate was 23.1 mL/min/1.73 m2. No hematuria was detected. Ultrasound examination and contrast-enhanced CT showed a 64-mm diameter juxtarenal AAA, not extending below the bifurcation of the abdominal aorta. The AAA was adjacent to the lowest of three left renal arteries (Figure 1), an RLRV, and a left retroperitoneal hematoma. The inferior vena cava was in the normal position on the right side of the aorta. Read more........

Significance of Congenital Coronary Artery Fistulas

Congenital coronary artery fistulas (CAFs) are anomalous terminations of coronary arteries in cardiac chambers or great arteries created by bypassing the myocardial capillary bed. CAFs are the second most common coronary anomaly after coronary artery origin anomalies. CAFs are mostly asymptomatic. However, CAFs may cause myocardial ischemia, angina pectoris, congestive heart failure, arrhythmias and infective endocarditis.

Previously, we presented a case of multiple coronary-cameral fistulas causing stable angina pectoris . A 65-year-old male patient referred to our outpatient clinic withchest pain and exertional dyspnea. The patient was suffering from retrosternal exertional chest pain for six months which relieved with rest. Previous medical history revealed hypertension and diabetes mellitus. Electrocardiogram showed inferolateral T wave inversion (Figure A) and echocardiography revealed normal left ventricular systolic function without left ventricular hypertrophy or cardiomyopathy. Coronary angiography was performed with an early diagnosis of coronary artery disease. Read more..........

Immunotherapy in Eosinophilic Granulomatosis with Polyangiitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss). EGPA has distinct features, namely asthma, common rhino-sinusal involvement, hypereosinophilia, tissue infiltration with eosinophils and necrotizing granulomatosis vasculitis.Conventional immunosuppressive therapy and glucocorticoids have been GPA and MPA standard of care for remission induction and maintenance for four decades. This regimen hastransformed the outcome from death to a strong likelihood of disease controland temporary remission. However, most patients have recurrent relapses that lead to damage and require repeated treatment. Cumulative side effects of immunosuppressive agents and glucocorticoids thus remain major causes of long-term morbidity, damage and death.

The development of therapeutic immunomodulation in systemic autoimmune diseases has shed new light on these complex diseases. Rituximab, an anti-CD20 monoclonal antibody that depletes Bcells in peripheral blood, has been shown to be not inferior to cyclophosphamide to induce remission in GPA and MPA patients, with an acceptable safety profile, leading to its registration by the EMA and FDA as drug remission-induction therapy in these patients. In addition the MAINRITSAN trial, conducted by the French Vasculitis Study Group, demonstrated that pre-emptive low dose rituximab given every 6 months for 18 months was significantly more effective than azathioprine standard of care to maintain remission in GPA and MPA, with a similar profile of tolerance. Such therapeutic immunomodulation has changed the standard of care for maintenance therapy in these vasculitides. Read more...........

Intracellular Zinc: A mediator of Vascular Aging and Disease?

Aging is a major risk factor in the development of cardiovascular diseases. Accumulation of waste materials like damaged mitochondria and decline in stress response mechanisms contribute to increased oxidative stress over time. The free radical theory of aging postulates that increased levels of reactive oxygen species [ROS] cause genomic and mitochondrial DNA damage leading to sustained oxidative stress that promotes tissue dysfunction and aging. In the cardiovascular system, NADPH oxidasesproduce ROS that are involved in normal function; however, overproduction ofROS by these enzymes, as well as decreased expression of antioxidant enzymes are associated with vascular dysfunction and disease.

Cellular senescence, a hallmark of mammalian aging, is a process of permanent cell cycle arrest  that has been linked to the development of age-related diseases, including atherosclerosis. A causative role for senescence in disease development was reported as the selective removal of senescent cells in vivo showed a delay in age-related diseases. Although senescent cells have lost their replicative capability, they possess a secretory and pro-oxidative/inflammatory phenotype  that likely contributes to organ dysfunction during aging.

It is well known that nutritional status plays an important role in disease development. Over-consumption of high calorie foods is a risk factor for diseases like metabolic syndrome, atherosclerosis and diabetes; however less is known about the consequences of micronutrient deficiencies in cardiovascular disease progression. Read more............

Reduced Cardiac Performance after Differential Pharmacological Stress in Streptozotocin-Induced Diabetic Rats

Diabetes Mellitus (DM) is a main risk factor for heart failure. A hallmark of this common complication is a disturbed conductibility of the left ventricle (LV). In this regard, diabetic cardiomyopathy is a significant entity, which could manifest as impaired cardiac performance in the absence of coronary artery disease, systemic hypertension or valvular heart disease that result from metabolic derangement present in diabetes. Among others, structural changes in extracellular matrixand myocyte damage contain hallmarks of this disease. Abnormalities in these compartments may result in left ventricular dysfunction (LV).

The Application of streptozotozin (STZ) to rats is a well established model of type 1 DM. We previously showed in this model severe impaired LV function under basal conditions in a chronic stage of STZ-induced DM. We further identified pathophysiological mechanisms, which could be responsible for this disturbed cardiac phenotype. This includes endothelial dysfuntion, cardiac fibrosis, inflammation and disturbed myocardial calcium regulation as well as neurohumoral activation.Whereas the cardiac phenotype under basal conditions in the chronic stage in STZ rats is well characterized, we analysed in the present study in vivo the time-dependent LV conductibility in this model. Therefore we measured LV function in STZ diabetic rats on two different time points under basal and under different pharmacological stress conditions using invasive LV microconductance catheter technique. Read more................

  

Putting Evidence Based JNC 8 Guideline into Primary Care Practice

The global hypertension prevalence is estimated to increase from 40% to 50% in the year 2025, with a significant upsurge in future morbidity and mortality due to heart disease and strokes. In the Kingdom of Bahrain, hypertension control has been achieved in only 1 out of 6 treated patients, which suggests that there is a major shortcoming either in clinician inertia or failure to take appropriate action to drive blood pressures ("BPs") down to guidelinerecommended levels.

We suggest that clinicians and the Ministry of Health ought to select one of the current guidelines and follow its recommendations. The Joint National Committeefor Hypertension Detection and Management updated the JNC 8 guideline (2013), which if followed correctly, will achieve enhanced patient management and improve outcome indicators. The JNC 8 panel has a different, focused and more simplified treatment approach than other expert panels, with a single BP recommendation (140/90 mm Hg) for both the pharmacologic treatment threshold and treatment goal for patients between the ages of 18 to 60 years old with/without diabetes ("DM") or chronic kidney disease ("CKD"). Furthermore, the JNC 8 relies solely on critical assessment of randomized controlled trials and reduces the number of first-line drugs from five to four. Nonetheless, guidelines are not a substitute for clinical judgment, and clinicians must consider each patient's circumstances and clinical condition when making decisions about medical care. Read more.............

Dysostosis Multiplex (Gm-1 Gangliosidosis: Type II)

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder characterized by the generalized accumulation of GM1 ganglioside, oligosaccharides, and the mucopolysaccharidekeratan sulfate (and their derivatives). Deficiency of the lysosomal hydrolase, acid β-galactosidase, causes GM1 gangliosidosis . GM1 gangliosidosis is a rare disorder, and theestimated incidence is 1:100,000-200,000 live births. GM1 gangliosidosis is found in all races, although specific alleles can be identified in certain ethnic groups. A high frequency of GM1 gangliosidosis has been reported from Southern Brazil, and a large number of Japanese patients with the adult form have been reported. All 3 types of GM1 gangliosidosis are inherited as autosomal recessive traits and have equal sex distributions.

Case Report: 5 years old boy with normal birth history born to a nonconsanginous parents, presented with mild developmental delay, gait difficulties and stiffness of limbs since 4 year of age. Initially parents noticed child had tiptoe walking, later he had stiffness of both upper and lower limbs which is gradually progressive. Child is still able to walk but unable to run. There is history of febrile seizures at 1.5 year of age. Younger sibling also having similar complaints.

On examination: Boy is alert, cooperative GPE revealed, Coarse facial features, proptosis, prominent forehead, tented upper lip, hepatosplenomegaly, melanotic patches over back, elbow, finger & hamstrings contracture, protrubrent abdomen with umbilical hernia, brisk reflexes, power 5/5 and spastic gait. Investigations: CBC showed normocytic hypochromic with mild relative monocytosis, LFT’ & RFT’s were normal, Urine test positive for MPS, Serum Hexosaminidase. A enzyme levels raised above normal limits, Aryl sulfatase negative, Beta galactosidase enzyme levels were reduced. Read more..............

Carvajal Syndrome: A Rare Variant of Naxos Disease

Carvajal syndrome also known as ‘Striate palmoplantar keratoderma with woolly hair and cardiomyopathy is a cutaneous condition inherited in an autosomal recessive pattern due to a defect in desmoplakin gene. The skin disease presents as a striate palmoplantar keratoderma particularly at sites of pressure. The patient is at risk of sudden cardiac death due to dilated cardiomyopathy associated with this entity. A variant of Naxos disease, reported as Carvajal syndrome,has been described in families from India and Ecuador. Clinically, it presents with the same cutaneous phenotype and predominantly left ventricular involvement.

Case Report:

11 years old boy presented with cough, breathlessness and easy fatigue ability for 3 months duration. On general examination the pt had fine brittlle lusterless scalp hair, pallor, stomatitis, keratotic skin over palm, sole and lower half of both lower limbs. Pt has tachycardia with HR 140/min, RR 40/min, BP 80/60 mmhg, SPO2 72%, raised JVP, with B/L basal crepitation’s, S3 gallop present. Echocardiographic examination revealed a dilatation of the right and left ventricles with a left ventricular ejection fraction of 35% and biventricular trabecular configuration, predominantly of the left ventricle and also grade I tricuspid and Mitral valve insufficiency (Figures 4 and 5). Patient was treated with diuretics, beta-blockers’ and ACE inhibitors. Read more..................

Atherosclerosis and Lipid Lowering: is there a Need for New Agents?

Cardiovascular disease (CVD) is the leading cause of death worldwide. Among well-known risk factors, such as visceral obesity, sedentary lifestyle, metabolic syndrome, smoking, hypertension, age, gender, family history of heart attacks, diabetes, low levels HDL-C, high levels of LDL-C and total cholesterol are very strong predictors of CVD events and death.In recent years, there have been significant advances in the elucidation of biomarkers of atherosclerotic disease, and also their pathogenesis, prevention and treatment. Atherosclerosis is a systemic inflammatory disease characterized by on-going progression in response to systemic risk factors and local pro-atherogenic stimuli that leads to acute myocardial infarction, stroke and lower limb ischemia. 

Statins has substantially reduced CVD events around the world and is recommended as first-line therapy for CVD management. However, a need for other lipid-loweringagents, because some patients do not tolerate statins due to adverse events, or cannot reach LDL-C level desired because of high levels of LDL-C, or patients with very high risk cardiovascular events need more intensive reduction therapy. Can we pay the benefits of these new agents when statins are effective and inexpensive?

Zhang et al. reported a meta-analysis study to evaluate the safety and efficacy of anti-PCSK9 antibodies in randomized, controlled trials (RCTs). Twenty-five RCTs encompassing 12,200 patients were included. The study showing largely no significant difference between anti-PCSK9 antibodies and placebo (or ezetimibe), except that alirocumab was associated with reduced rates of death (relative risk (RR): 0.43, 95 % CI: 0.19 to 0.96, P =0.04) and an increased rate of injection-site reactions (RR: 1.48, 95 % CI: 1.05 to 2.09, P =0.02); evolocumab reduced the rate of abnormal liver function (RR: 0.43, 95 % CI: 0.20 to 0.93, P =0.03), both compared with placebo. Evolocumab and alirocumab substantially reduced the LDL-C level by over 50%, increased the HDL-C level, and resulted in favourable changes in other lipids. Read more.............

A Forum for Vasculitis Researchers from East to West, from Bench to Clinic

Is vasculitis research important? Do we need an open access journal for vasculitis? The answers to both questions are yes, vasculitis research is important and we need an open access journal for vasculitis and only vasculitis. But why and how? The vasculitides represent a wide range of diseases, from vasculitis involving skin only to systemic large vessel arteritis without any superficial signs. This group of diseases are highlydiverse and some are rare with an annual incidence between 1/10, 000 to1/1,000,000. This disease term may arouse fear in not only patients but also general practicing physicians. Some vasculitis such as Henoch-Schonlein purpura is relatively common and self-limited; while some vasculitis like anti-neutrophil antibody associated vasculitis (AAV) is rare but associated with severe consequences. In clinical practice, vasculitis can be difficult to be diagnosed. 

For example, patients with granulomatosis with polyangiitis (GPA) can present with sinus, lung, kidney or nervous system involvements. Due to the diversity and highly variable responses to treatment of some vasculitis, the learning curve progress slowly.The clinical diagnosis of vasculitis relies on a constellation of clinical manifestations, serologic markers and pathology study. The sensitivity and specificity of classification/diagnosis criteria can be influenced by local disease incidence and prevalence.To understand the economic burden of disease, epidemiology study can provide some valuable insights. However, the distribution map of vasculitides is largely unfilled. One of the famous examples that shows the importance of epidemiology studies is the Sily Road disease-Behcet’s disease, which distributes mainly from Turkey to Japan, implies the impact of population migration or even a transmissible pathogen; we need more evidence to confirm these disease spread model. Read more......................