Undiagnosed myopathy before surgery and safe anaesthesia table

Patients with muscle pathology are a challenge for anaesthesiologists because of possible life-threatening general anaesthesia complications. A review of the current medical literature on the issue clearly indicates that increasing awareness by anaesthesiologists in recent years has led to a reduction in the occurrence of adverse events in patients with diagnostically well-defined muscle disease. On the other hand, the current emerging aspect is that the great majority of complications concern subjects with clinically non-overt (silent to mildly symptomatic) and thus undiagnosed myopathy. With a view to improving prevention of possible critical anaesthesia complications in such patients, we present a "Safe Anaesthesia Table", listing both the anaesthetic drugs to be avoided and those considered harmless for myopathic patients, irrespective of age and type of pathology. In addition, a brief outline about the clinical aspects suggestive of a possible muscle pathology is also provided. Using "safe drugs" during routine surgical procedures in subjects with suspected undiagnosed myopathy will enable the anaesthesiologist to avoid delaying surgery, while protecting them from anaesthesia complications. By following this approach the presumed myopathy can be properly investigated after surgery.Key words: anaesthesia complications, undiagnosed myopathy, safe anaesthesia, hyperCKemiaPatients suffering from a variety of Muscle Diseases can experience critical adverse events during and after general anaesthesia. Usually these complications are triggered by volatile anaesthetics or succinylcholine. In some myopathic patients, however, life-threatening side effects may also be precipitated by other agents, namely anticholinesterase and neuroleptic drugs (1-6). All complications can be unpredictably combined and present with different clinical severity. As described in a systematic review by DeVries et al. (7), side effects of anaesthetic drugs currently represent 2% of all in-hospital untoward episodes, the decrease being mainly due to extensive use of total intravenous anaesthesia and reduced administration of succinylcholine (1-4). Nonetheless, in view of the possible fatal outcome, they remain a major concern for anaesthesiologists.Acute rhabdomyolysis with the resultant myoglobinuria is among the most severe anaesthesia-related complications for children and adults with muscle pathology. The syndrome may occur alone or as the culmination of a typical episode of Malignant Hyperthermia (MH). Susceptibility to this life-threatening syndrome is an uncommon pharmacogenetic muscle disorder characterized by altered calcium release from the sarcoplasmic reticulum. Besides rhabdomyolysis and myoglobinuria, the complete clinical manifestation of an MH event includes muscle rigidity, high body temperature, metabolic acidosis, hyperkalaemia, and cardiac arrhythmia. Notably, apart from anaesthesia-related MH episodes, susceptible subjects are basically asymptomatic, even though about half of them present raised serum CK (3, 4, 8). Succinylcholine and volatile anaesthetics may trigger a typical MH crisis also in patients with other genetic disorders, as Central Core Disease, a rare congenital myopathy allelic to MH Susceptibility (2, 3, 5). Acute rhabdomyolysis with myoglobinuria mimicking an MH episode, albeit incompletely, is more frequently described in patients with muscular dystrophy and usually referred to as an MH-like episode (1, 2, 9). These episodes are often complicated by hyperkalaemia and severe cardiac arrhythmia, clinical events that have also been reported for other muscle pathologies, as metabolic muscle disorders, congenital myopathies and channelopathies (3, 10-18).Cardiac and respiratory complications are highly critical side effects potentially experienced by myopathic patients, both during and after general anaesthesia. Their occurrence is directly linked to the frequency of underlying ventilatory muscle pathology and cardiac involvement present in muscular dystrophies and related disorders. Volatile anaesthetics may determine heart complications through a calcium-related cardiodepressive effect and a complex dysrhythmic action. Succinylcholine and other depolarizing agents can induce hyperkalaemia followed by fatal ventricular arrhythmia. Serum potassium may also be increased by anticholinesterase drugs (1, 2, 19).Other critical side effects of anaesthetic agents are characterized by myotonic reactions, muscle spasms and localized or generalized rigidity (1-6). Myotonia and related clinical manifestations are usually caused by depolarizing muscle relaxants, but can also be determined by anticholinesterase drugs (1-4, 18). The latter can also enhance vagal responses that aggravate possible autonomic dysregulation. Myotonic reactions induced by succinylcholine or anticholinesterase drugs are often localized to the masseter muscles, but exacerbation may lead to life-threatening respiratory muscle involvement (18). Jaw muscle stiffness may also result from prolonged masseter contraction without electrical activity (spasm): this sign has to be carefully evaluated because possible onset of generalized rigidity, culminating in an MH episode (1-5). Widespread muscle rigidity, associated with central nervous system-induced hyperthermia, can be determined by neuroleptic drugs (butyrophenones and phenothiazines). Accordingly these substances are currently mostly replaced by propofol and opioids (1-4).There are no available population studies on the prevalence of anaesthesia complications in myopathic subjects. Nonetheless, the extent of the problem is illustrated by recent observations on overall prevalence of genetic myopathies, indicating an index of about 1 case per 2,500 inhabitants (20). This estimate is higher than previous data reviewed by Emery in 1991 (21), likely because of the prolonged life expectancy of myopathic patients, e.g. those with Duchenne Muscular Dystrophy (DMD), and because the clinical diagnosis of pauci- or mildly symptomatic patients has been facilitated by the widespread use of DNA molecular analysis.Nowadays in Italy, as in other Western countries, patients with overt myopathy are usually admitted to surgery with a precise diagnosis. Consequently, thanks to specific preventive measures diffusely adopted by anaesthesiologists, potential anaesthesia-associated side effects seem on the whole to have decreased (2-4, 6, 9, 13, 22-26). On the other hand, analysis of recent reports (5, 6, 11, 15, 17, 25, 27) indicates that complications in patients with undiagnosed myopathy are the emerging aspect of the issue, with particular evidence in the extensive review published by Gurnaney et al. (25) on intra- or post-operative rhabdomyolisis, cardiac arrest and hyperkalaemia in myopathic patients. By examination of 173 references, the Authors focused two remarkable points: 1) the great majority of complications involved subjects with undiagnosed myopathy; 2) nearly all the observations concerned patients with DMD or other dystrophinopathy. They were predominantly pauci- or very mildly symptomatic patients, in whom myopathy had been simply overlooked, and the eventual diagnosis of muscular dystrophy pursued on account of the adverse reaction to anaesthesia. Such a high overall level of undiagnosed myopathy was unexpected. A similar observation, that easily escaped general attention because published in a German- language journal, was also previously reported by Breucking et al. (26). Said investigation on 221 patients with DMD or another dystrophinopathy found that severe anaesthesia-related side effects occurred only in children or adolescents with undiagnosed dystrophinopathy.Minimal to mild symptoms of myopathy may also characterize the clinical phenotype of manifesting carriers of dystrophinopathy or other muscular dystrophy, as calpainopathy or dysferlinopathy (28-30). Due to non-overt symptomatology, these carriers could hypothetically go unrecognized at admission to surgery, with the high-risk of anaesthetic complications similar to those in patients with undiagnosed myopathy. This inference has been confirmed by recent literature which indicates at least two cases of anaesthesia-related critical events in carriers of dystrophinopathy (31, 32). To our knowledge , similar data have not yet been reported for other muscular dystrophies.On the whole, currently available data on muscle disease and related anaesthesia complications suggest that the patients involved are mostly those with Clinicallyunclear, because silent or pauci- to mildly symptomatic, Undiagnosed Myopathy (CU Myopathy). With a view to improving prevention of possible critical anaesthesia complications in such patients, we present a list of anaesthetic drugs considered harmless to them ("Safe Anaesthesia Table"). Essential indications are also provided on clinical aspects suggestive of myopathy.     

A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease

Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.Key words: Early-onset Pompe disease, Acid maltase deficiency, Founder effectGlycogen storage disease type II (Online Mendelian Inheritance in Man, OMIM, accession number 232300), also called Pompe disease, was described by Johannes C. Pompe in 1932. The disorder is caused by a deficiency of the enzyme acid alpha-glucosidase (acid maltase, EC 3.2.1.20, Swiss) which originates lysosomal glycogen accumulation leading to lysosomal swelling, cellular damage and dysfunction (1-3). Affected individuals develop progressive neuromuscular damage, showing a debilitating and frequently fulminating course on the classical, early-onset type of the disease. Other main findings are hypertrophic cardiomyopathy, hypotonia, hepatomegaly, macroglossia, feeding problems and breath difficulty. Currently it is recognized that the late form of Pompe disease has a very variable phenotype that can be confused with a wide range of neuromuscular, pulmonary and cardiovascular diseases with mild, moderate or severe symptoms that present either alone or combined (4-6).Pompe disease has an autosomal recessive inheritance and it is caused by more than 300 mutations that occur all over the gene coding for acid alpha-glucosidase (GAA) located at locus 17q25.2q25.3. The molecular phenomenon responsible of the different types of clinical expression occur by the presence of two either homozygous or compound heterozygous pathogenic mutations in early-onset Pompe cases, whereas late-onset Pompe have one variant and one pathogenic mutation (7). The majority of disease-causing mutations are unique; nonetheless, relatively frequent mutations have been described in certain populations with a possible founder effect traced from the original mutated carrier to the newly occurring cases. Affected cases have been described worldwide with a few high-prevalence regions like South-Africa, Taiwan and Holland (1, 8-10).Herein, we described two unrelated cases affected with classical early-onset Pompe disease, both pertaining to the same small Mexican region, with the same novel homozygous frameshift mutation at gene GAA (c.1987delC), identified by complete gene sequencing.     

Hypertensive retinopathy and its association with cardiovascular,renal and cerebrovascular morbidity in Congolese patients

Hypertension is a major public health problem worldwide and on the African continent.1,2 The disease, once considered to be rare outside Europe and North America, is now a leading cause of disability and mortality in developing countries. Its prevalence is projected to reach 30% worldwide by 2025.2Poor control of hypertension increases the likelihood of complications affecting the cardiovascular and cerebrovascular systems, kidney and retina, often labelled under the term target-organ damage (TOD).1 The development of subclinical TOD, such as left ventricular hypertrophy (LVH), increased intima–media thickness of the large vessels, microalbuminuria following glomerular dysfunction, cognitive decline and hypertensive retinopathy precedes the occurrence of major complications, which include stroke, congestive heart failure and myocardial infarction, renal failure and retinal vascular occlusions.3-5 In the Democratic Republic of Congo (DRC), the prevalence of systemic hypertension has been reported to be over 25%,6,7 whereas hypertension and associated complications account for over 20% of deaths among adults.8Studies have demonstrated that TOD increases cardiovascular risks over that already associated with elevated blood pressure alone. For example, it has been shown that once LVH has developed following long-standing systemic hypertension, it behaves as an independent risk factor and a predictor of both further cardiac complications,9 and other incident vascular events such as ischemic stroke and myocardial infarction.10 Similarly, the presence of cerebrovascular and renal damage may raise cardiovascular risk over that conferred by hypertension itself.11,12In addition, hypertensive retinopathy has long been known as a predictor of systemic morbidity and mortality. Both epidemiological and clinical studies have provided evidence that markers of hypertensive retinopathy are associated with raised blood pressure, systemic vascular diseases, and subclinical cerebrovascular and cardiovascular disease, and predict incident clinical stroke, congestive heart failure and mortality due to cardiovascular complications.13 This association of hypertensive retinopathy with other TOD has also been shown to be independent of blood pressure and other risk factors, which supports the recommendation that retinal vascular changes should be assessed in individuals with systemic hypertension for better extra-ocular TOD risk stratification.13While the number of reports on hypertensive TOD has been on the rise on the African continent, the relationship between hypertensive retinopathy and other TOD has largely remained unexplored. The aim of this study was to examine the association of hypertensive retinopathy with LVH, chronic kidney disease (CKD) and stroke in Congolese patients.     

Impact of prehypertension on left ventricular mass and QT dispersion in adult black Nigerians

The heterogeneity of individuals with blood pressure (BP) < 140/90 mmHg in terms of cardiovascular (CV) risk was reported as early as 1939 by Robinson and Brucer.1 BP in the range of 120–139/80–89 mmHg (labelled then as prehypertension) was observed to be associated with high risk of progression to hypertension (HT) and cardiovascular disease (CVD) later in life when compared with BP < 120/80 mm Hg.1The term prehypertension was adopted in May 2003 by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High blood Pressure (JNC-7) to describe BP range of 120–139/80–89 mmHg.2 The resuscitation of this terminology/concept in JNC-7 was a sequel to the documentation of a higher morbidity in individuals with prehypertension in landmark publications.3-5 Prehypertension (PHT) was defined in JNC-7 not only to emphasise the excess risk associated with BP in this range, but also to focus increased clinical and public health attention on prevention.2,6,7Prevalence rates of PHT among adults in the United States, Ghana and northern Nigeria have been reported to be 31, 40 and 58.7%, respectively.7-9 In most studies, including the ones above, PHT was more prevalent than hypertension.7-9 Though PHT is associated with increased risk of major CV events independently of other CV risk factors,10 most individuals (90%) with PHT have at least one cardiovascular risk factor such as dyslipidaemia, abdominal obesity, hyperinsulinaemia, impaired fasting glucose levels, insulin resistance, a prothrombotic state, tobacco use, endothelial dysfunction, and impaired vascular distensibility.6,7,9,10QT interval dispersion (QTd) (the difference between the longest and the shortest QT intervals on a surface ECG), when excessive, is associated with increased risk of cardiovascular morbidity and mortality in population studies, and many clinical conditions, including hypertension.11,12 This has been related to ventricular electrical instability, providing the necessary substrate for lethal ventricular arrhythmias.12,13 Greater QTd and left ventricular mass have been demonstrated in hypertensive individuals compared with normal individuals.11,13,14Considering the well-established, linear relationship between BP and the risk of cardiovascular events, the CV risk associated with PHT is intermediate between normotension and hypertension.2,03 Hence, electrocardiographic and echocardiographic indices of target-organ damage in PHT may also be intermediate between normotension and hypertension. The aims of this study were: (1) to compare the QTd and indices of left ventricular hypertrophy in adult black normal and prehypertensive subjects, and (2) to evaluate the relationship of QTd with electrocardiographic and echocardiographic indices in these subjects.     

A heroin addict with focal weakness

A 24-year-old female with 5 year history of heroin abuse experienced painless stiffness of elbow joints and weakness of shoulder and upper limb muscles. She was injecting herself 4-6 times daily alternatively in the upper extremities, sparing the lower limbs. Electromyography (EMG) showed myopathic changes in clinically affected and unaffected muscles. Magnetic resonance imaging (MRI) revealed muscle fibrosis in directly injected muscles, whereas in subcutaneous fat and within muscles of anterior and posterior compartments of both thighs, not directly injected, there were signal changes supportive of oedema and inflammation. EMG and MRI were congruent in showing abnormalities in muscles not directly injected, suggesting long distant effects of heroin or adulterants with a mechanism either toxic or immunologically mediated.Key words: Heroin myopathy, focal myopathy, muscle fibrosisThe earliest reports of muscle fibrosis at sites of intramuscular opioid injection involved pentazocine; a proposed mechanism was focal precipitation of acidic drug (1, 2). Human and animal studies demonstrated that heroin may cause fibrotic myopathy, similarly to pethidine, piritramide, and meperidine (1, 2) in muscles chronically injected.     

Prevalence of hypertension in the Gambia and Sierra Leone,western Africa: a cross-sectional study

Hypertension (HTN) is a chronic, slowly progressive disease affecting about one billion people globally and leading to about 7.1 million deaths annually. People of African origin may be particularly susceptible to hypertension.1-3 Defined as a sustained systolic blood pressure (SBP) above 140 mmHg, a diastolic blood pressure (DBP) above 90 mmHg or both, the aetiology of HTN can be classified as primary or secondary. While there is no known cause for primary (essential) HTN, which accounts for 90–95% of cases, the remaining 5–10% of cases is defined as secondary HTN and is caused by other disease conditions, which may affect the renal, circulatory, endocrine or other organ systems.Many factors are associated with, and may contribute to the development and persistence of primary HTN, including obesity, stress, smoking,4 low potassium intake, high sodium (salt) and alcohol intake,5,6 familial and genetic influences,7,8 and low birth weight.9 On the other hand, hyperthyroidism, hypothyroidism and other conditions causing hormonal changes may be associated with primary pulmonary HTN.10,11 Regardless of the cause, the consequences of HTN include renal failure, heart failure, myocardial infarction, pulmonary oedema and stroke.12Given these undesirable outcomes, treatment and prevention have assumed increasing emphasis in the management of HTN. Modification of risk factors can be achieved by reducing body weight and decreasing sugar intake, along with lowering alcohol consumption,13,14 as well as reducing salt intake and increasing potassium intake.15,16 Secondary HTN is managed by treating the underlying cause. Drugs available for the treatment of HTN, whether primary or secondary, include calcium-channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), diuretics, α-blockers and β-blockers.Race and ethnicity may influence pathogenesis, prevalence and treatment of HTN,17 perhaps through genetic influences. As a consequence, HTN remains one of the most common CVDs in Africa and one of the most frequent causes of death in the sub-Saharan African region.18,19 In 2000, the rate of HTN in sub-Saharan Africa was reported to be 26.9% in males and 28.3% in females.20 Low socio-economic status (SES) may additionally play an important role in the high prevalence of HTN in western and sub-Saharan Africa.A cross-sectional survey in Tanzania revealed that treatment rates for HTN were very low, especially among people with low SES.21 Low SES led to inadequate education levels as a factor correlating with a higher blood pressure (BP) in adults and resulted in a low treatment rate for HTN due to monetary issues.22Stress, in addition, was another factor related to HTN prevalence, especially in Africa.23 It has been shown that psychosocial stress affects the L-arginine/nitric oxide (NO) system, with a higher susceptibility in black Africans, which in turn contributes to a higher risk of CVD in those individuals.24Therefore, a multiplicity of factors may be associated with and contributing to a high prevalence of HTN among Africans. The current study was undertaken to determine and quantitate the prevalence of HTN in two countries in western sub-Saharan Africa, namely, the Gambia and Sierra Leone.     

Diagnostic value of plasma C-type natriuretic peptide levels in determination of the duration of mesenteric ischaemia

Acute mesenteric ischaemia (AMI) causes significant morbidity and mortality if not promptly diagnosed and treated. If medical interventions are delayed, the patient may sustain serious ischaemic injury leading to bowel necrosis, so large segments of bowel may require surgical resection. Often these patients have poor clinical outcomes and suffer from complications such as malnutrition.1,2 Mesenteric ischaemia makes up 0.1% of all hospital admissions.1 Even though technological advances have been made in diagnostic laboratory and imaging techniques, AMI remains fatal in 60% of patients diagnosed with this condition.1,3Scientists have been investigating whether there are specific sensitive biomarkers that may indicate the presence of AMI.2,4 Several endothelial markers have been identified as putative biomarkers that may reveal the severity and duration over which mesenteric ischaemia has been sustained.5 However, markers that are effective enough for use in clinical practice have yet to be identified.Natriuretic peptides, namely atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) function in maintaining fluid and electrolyte balance as well as blood vessel tone. CNP is released by vascular endothelial cells, and this biomarker’s function in influencing vascular tone has been investigated.8,7 It has been hypothesised that CNP is an endothelium-derived hyperpolarising factor (EDHF) that specifically affects the degree of resistance in the mesenteric arteries.8 In this study, we aimed to investigate plasma CNP levels during early and advanced stages of mesenteric ischaemia so as to determine whether CNP levels are a good indicator of severity of AMI in a rat model.     

An echocardiographic study of infective endocarditis,with special reference to patients with HIV

Important developments during the last 20 years have facilitated rapid and accurate diagnosis of infective endocarditis (IE), and recent guidelines emphasise the role of early surgical treatment when complications supervene.1,2 The emergence of prosthetic valve endocarditis, catheter-related endocarditis, and an increased incidence of antibiotic resistance has led to new challenges for the physician.3 From a microbiological standpoint, the rise in staphylococcal infections, and the immune paresis associated with HIV infection pose further diagnostic challenges that also have important implications for management.3Bacteraemia is said to be common in HIV-positive patients, due to the numerous immunological defects present in this disease.4 Furthermore, in the setting of HIV exposure and altered immunity, infection is not uncommonly caused by unusual organisms, such as barbonella, salmonella, and listeria.1 This raises the question as to whether IE presents a somewhat different clinical and echocardiographic picture in the HIV-positive patient.It is known that the degree of immunosuppression, manifested by a reduced CD₄ lymphocyte count, strongly correlates with the presence of echocardiographic abnormalities.5 Whether the immunosuppression associated with HIV may alter the clinical picture of valvular heart disease, particularly IE, is not clear. Since a decrease in CD₄ count is thought to predispose to HIV-associated cardiac disease, this study was designed to determine the pattern of cardiac involvement in the HIV-infected subjects who develop IE.5,6     

Prevalence of anaemia among patients with heart failure at the Brazzaville University Hospital

Heart failure (HF) is a frequent cause of hospitalisation in cardiology. Its prognosis depends on several factors, including anaemia, which is common among patients with heart failure.1 Anaemia is an independent prognostic factor for mortality in chronic HF and is associated with higher rates of mortality, hospitalisation and re-admission.2,3 Anaemia is a powerful independent predictor of death and hospitalisation in systolic and diastolic dysfunction.2,4-7In order to improve the management of patients suffering from systolic and diastolic HF, it is critical to understand the relationship between HF and anaemia, and the possible outcomes. The aim of this study was to determine the prevalence of anaemia in patients with heart failure and to evaluate its impact on the prognosis of patients in Brazzaville, Congo.     

Cardiac surgery for patients with heart failure due to structural heart disease in Uganda: access to surgery and outcomes

Improvement in the control of infectious diseases and malnutrition associated with changes in lifestyle has led to a new epidemiological pattern in many low- and middle-income countries. Non-communicable diseases, mainly cardiovascular disorders, have emerged as major causes of morbidity and mortality in most sub-Saharan African countries.1 Hospital-based studies indicate that heart failure (HF) accounts for 3–7% of all admissions to African hospitals.2,3-7Although there has been increasing interest in the epidemiology of cardiovascular diseases in the African continent,7-9 recent data from Uganda are scarce7,10 but most needed to guide public health policies. Most registers originate from South Africa and cannot be transposed to poorer sub-Saharan countries.2,11Echocardiography is a mainstay in the assessment of HF. Unfortunately, access to echocardiography remains limited in many African countries due to cost and lack of skilled health workers, thereby leading to little data on cardiovascular diseases.12We report on the distinctive patterns of HF through a prospective, cross-sectional, hospital-based study in patients referred for suspected heart disease in urban Kampala, Uganda, in order to characterise the features of HF and to tailor future interventions. We also aimed at assessing access to invasive interventions and outcomes in patients with surgical indications.     

Simultaneous coronary artery bypass grafting and carotid endarterectomy can be performed with low mortality rates

There is controversy over the best approach for patients with concomitant carotid and coronary artery disease.1 Therapeutic strategies include isolated coronary artery bypass grafting (CABG), staged carotid endarterectomy (CEA) and CABG, reversed staged CEA and CABG, and simultaneous procedures under single anaesthesia.2Although reported experiences over three decades are available, combining CEA with CABG remains to be elucidated.3 Furthermore, risk of cerebrovascular accident (CVA), which is one of the major predictors of prognosis of CABG, has been reported to increase up to 14% in patients with severe carotid artery stenosis (> 80%).4-9Peri-operative neurological events such as stroke after CABG are the major neurological complications, which increase with age.10 The incidence of peri-operative stroke has been well documented at approximately 2% of all cardiac surgeries.11 Despite reduced overall complication rates over the years after CABG, the incidence of stroke remains relatively unchanged.10The aetiology of peri-operative stroke is multi-factorial including hypotension or hypoperfusion-induced reduced brain flow, atherosclerosis due to micro- or macro-embolisation, and intra- or extra-cranial vascular diseases.5 In addition, carotid artery disease is a critical factor; however, it is considered unlikely to be the only culprit for peri-operative strokes.12Although no consensus on the optimal management of patients with concomitant carotid and coronary artery disease has been reached,13 simultaneous CEA and CABG surgery is often associated with low rates of mortality and morbidity.14-17 In this study, we report our experience with simultaneous CEA and CABG surgery in our clinic in the light of data in the literature.     

Evaluation of left atrial mechanical function and atrial conduction abnormalities in Maras powder (smokeless tobacco) users and smokers

Tobacco use can be classified into smoking and smokeless tobacco. Smokeless tobacco is chewed or is absorbed by the nasal and oral mucosae. A type of smokeless tobacco called Maras powder (MP) is used mostly in the south-eastern region of Turkey, and in many cases users become addicted. It is obtained from a tobacco plant species known as Nicotiana rustica Linn. Nicotine concentrations in the tobacco used to produce MP are eight to 10 times higher than those in tobacco used to produce cigarettes.1 MP and its negative effects on the cardiovascular system have been well studied. MP is consumed in such a way that increase in oxidative stress is inevitable and as a result it accelerates the atherosclerotic process.2,3Cigarette smoke includes nicotine and toxic substances such as carbon monoxide and polycyclic aromatic hydrocarbons.4 Inhalation of these substances predisposes to several different atherosclerotic syndromes,5,6 and is also associated with the occurrence of cardiac arrhythmia.7,8The pathophysiological mechanism of cigarette smoking-induced cardiac arrhythmia is complicated, and the pro-fibrotic effect of nicotine on myocardial tissue with its consequent increased susceptibility to catecholamines, may play a role. Moreover, other components of cigarette smoking, such as carbon monoxide, as well as oxidative stress, are likely to cause the generation of arrhythmias. It is also known that cigarette smoking leads to cardiac autonomic dysfunction,9 and it has been implicated in prolonged QT intervals in healthy individuals.10 However, the nicotine concentration in the blood is more likely to cause the pro-arrhythmic effect of cigarette smoking.7,11 The risk of atrial and ventricular arrhythmia rises due to increased nicotine levels.9-12The prolongation of intra- and inter-atrial electromechanical intervals and the inhomogeneous propagation of sinus impulses are well-known electrophysiological characteristics of atria that are prone to fibrillation.13 Left atrial (LA) volume and LA mechanical function have recently been identified as a potential indicator of cardiac disease and arrhythmias.14,15 Prolongation of atrial electromechanical interval and impaired LA mechanical function are associated with adverse clinical events, including atrial fibrillation, stroke, diastolic dysfunction and left ventricular failure.16,17LA mechanical function and atrial conduction abnormalities have not been investigated in MP users and smokers. Therefore, our study was planned to evaluate whether MP damages intra- and inter-atrial conduction intervals and LA mechanical function as much as cigarette smoking.     

Rationale and design of the Pan-African Sudden Cardiac Death survey: the Pan-African SCD study

For many years there has been a debate about the definition and nature of ‘sudden death’ or out-of-hospital cardiac arrest.1-8 Issues pertaining to this debate have been the temporal definition of ‘sudden’, whether death was unexpected, whether death was witnessed, and the aetiology of the event. The time frame used to describe the duration of the terminal event initially was 24 hours. The current definition of sudden cardiac death (SCD) describes death within one hour of the onset of symptoms,2 since this period seems to describe most accurately patients with arrhythmic sudden cardiac death.9A very difficult issue is the classification of unwitnessed deaths. Most authors have erred in favour of classifying such events as SCDs, even though it is often impossible to determine when the patient was last seen alive or the duration of symptoms prior to death. Hence, SCD can be defined as follows: ‘Natural death due to cardiac causes, heralded by abrupt loss of consciousness within one hour of the onset of acute symptoms’. Pre-existing heart disease may have been known to be present, but the time and mode of death are unexpected.1The incidence of SCD occurring out of hospital varies with age, gender and presence or absence of cardiovascular disease. Incidence rates of SCD between 0.36 and 1.28 per 1 000 inhabitants per year have been reported in Europe and the United states.10-13 In these studies, only witnessed victims seen or resuscitated by the emergency medical services are included; these data therefore underestimate the incidence of SCD in the general population. Sudden cardiac death is responsible for about 300 000 to 400 000 deaths per year in Europe and the United States, respectively.14Several diseases linked with sudden cardiac arrest (SCA) have been reported.15,16 Autopsy studies in unselected subjects suggest that about two-thirds of such deaths are cardiac in origin, with coronary artery disease and its complications accounting for the overwhelming majority of deaths in the industrialised world.17,18 Indeed, coronary artery disease (CAD) is the leading cause of sudden death worldwide.3In Europe, cardiovascular diseases (CVD) account for around 40% of all deaths under the age of 75 years. SCA is responsible for more than 60% of adult deaths from ischaemic heart disease (IHD).2 Conversely, in young populations under 40 years, inherited ‘arrhythmogenic’ cardiac disorders are the main cause.8 The initial recorded rhythm in patients presenting with a sudden cardiovascular collapse is ventricular fibrillation (VF) in 75 to 80%, whereas bradyarrhythmias and asystole are thought to contribute to a minority of SCDs.4,16     

Vascular calcification is not associated with increased ambulatory central aortic systolic pressure in prevalent dialysis patients

Vascular calcification (VC) is a novel vascular risk factor strongly associated with mortality in dialysis patients.1,2 Although various explanations exist for this association, one mechanism is through alterations in pulse-wave velocity (PWV). Vascular calcification is associated with increased aortic PWV,3 which in turn is associated with raised central aortic systolic pressure (CASP) and reduced coronary perfusion.4,5 As a result, brachial pressure may significantly under- or over-estimate central pressure.6Not surprisingly therefore, central blood pressure parameters have been shown to predict hard cardiovascular endpoints (including mortality) better than concomitant brachial measurements.7-10 Whether vascular calcification is directly linked to central pressures is, however, unknown since there are many determinants of aortic stiffening other than calcification. Furthermore, a primarily damaged and stiff aorta may be the target for secondary deposition of calcium.11CASP can be calculated using applanation tonometry-derived peripheral pulse waveforms and associated software.12 This avoids the obvious disadvantages of invasive central pressure determination. The major disadvantage of standard techniques, however, is the one-dimensional static measurement that is obtained, with no information on ambulatory values or nocturnal dipping status.Loss of normal nocturnal systolic blood pressure dipping is prevalent in chronic kidney disease (CKD) and likely contributes to cardiovascular disease.13 Dipping, which can only be assessed using ambulatory monitoring techniques, correlates better with left ventricular mass index (LVMI) in end-stage renal disease than office-based blood pressure measurement.14,15There have been calls for the routine use of ambulatory blood pressure monitoring (ABPM) in clinical studies of CKD13,16 and indeed, for investigations into the utility of ambulatory CASP in clinical practice.17,18 Combining both ambulatory and central pressure measurements is an attractive strategy, but until recently has not been technically possible.A non-invasive wrist watch-like device, BPro with A-Pulse CASP software (HealthStats, Singapore) was recently approved by the US Food and Drug Administration (FDA: K072593) for the measurement of CASP as well as ambulatory blood pressure. It is a small, wrist watch-like, cuffless monitor which obtains radial pressure waveforms by applanation tonometry. BPro has the ability to measure ambulatory CASP and although not yet commercially available, the manufacturer is able to convert data into ambulatory CASP using the same software.As part of a recently published study on vascular calcification,19 we sought to prospectively evaluate whether the presence of vascular calcification had any relationship with ambulatory CASP in our young CKD-5D cohort using the BPro® radial pulse-wave acquisition device. We also sought to determine the utility of inter-dialytic office brachial and central blood pressure measurements in predicting ambulatory parameters.     

Hypogonadism and erectile dysfunction in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults. It affects many organs and systems besides muscle. Aim of this study was to assess frequency of erectile dysfunction (ED) and hypogonadism, the correlation between them and the impact of ED on quality of life (QoL) in patients with DM1. A series of 25 men (aged from 22 to 58 years) with a diagnosis of DM1 was analyzed. Muscular Impairment Rating Scale (MIRS) was used to assess severity of muscular involvement. Erectile function was assessed using the short form of the International Index of Erectile Function test (IIEF-5). Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were assessed. All patients completed the Serbian version of the SF-36 questionnaire as a measure of health-related QoL. ED was present in 18 (72%) of patients. Seven (28%) patients were euogonadic, 16 (64%) had compensated hypogonadism and 2 (8%) had primary hypogonadism. ED was somewhat more common in patients with hypogonadism (78% vs. 57%). Mental composite score of SF-36 was lower in patients with ED (p<0.05). Our results showed that 72% of men with DM1 had ED and hypogonadism. Studies with larger number of subjects are needed to resolve cascade of events that lays behind ED in DM1. Development of therapeutic strategies may have positive impact on QoL. Substitutive therapy with androgens may be benefitial.Key words: myotonic dystrophy type 1, erectile dysfunction, hypogonadisMyotonic dystrophy type 1 is the most common form of muscular dystrophy in adults with estimated prevalence of 1 to 35 patients on 100 000 inhabitants (1). It is an autosomal dominant disorder caused by expansion of unstable trinucleotide CTG repeats in DMPK gene on the long arm of the chromosome 19 (2). This mutation is responsible for premature aging of many organs and systems in DM1 (2). Endocrine disorders are common in DM1 (3). Hypogonadism is also described with affection of both interstitial and tubular gonadic function (4).Erectile dysfunction (ED) is defined as a persistent or recurrent inability to achieve and maintain a penile erection adequate for satisfactory sexual activity (5). It is reported that ED can be found among DM1 patients (6, 7), but there are not enough data about frequency and causes of this disorder. Also, effects of ED on personal and social life, as well as on quality of life (QoL) in DM1 men is still unclear.Aim of this study was to assess frequency of erectile dysfunction (ED) and hypogonadism, the correlation between them and the impact of ED on health-related QoL in patients with DM1.     

In vitro effects of sodium nitroprusside and leptin on norepinephrine-induced vasoconstriction in human internal mammary artery

Coronary heart disease (CHD) and stroke are the largest contributors to global mortality in low-, middle- and high-income countries as a result of current lifestyles. They will continue to cause decreased quality of life and contribute to the causes of morbidity and mortality throughout the world.1,2CHD, also known as coronary artery disease, is the narrowing of coronary arteries, hampering blood and oxygen supply to the heart when plaque builds up in the arteries. The heart is an aerobic organ and disruption of its normal oxygen supply causes irreversible changes in heart tissue. If the disruption of oxygen supply is severe, this becomes life threatening.3Although CHD cannot be cured, there are several treatment options to relieve the symptoms and reduce the progression and risk of complications (heart attack), and thereby prolong the expected lifespan. Treatment options include lifestyle changes and medication, but depending on the severity of the disease, more aggressive treatment methods including interventional procedures (angioplasty and stenting) or coronary artery bypass surgery are warranted.4Revascularisation by coronary artery bypass graft (CABG) surgery is a process of restoring the blood flow around existing blockages to the heart using autologous bypass grafts (or artificial grafts). The immediate success of this procedure is related to surgical technique and the anatomical characteristics of the grafted coronary artery.5 After grafting, the vascular smooth muscle cells of the new vessels are the primary regulators of vascular tone. Therefore characterisation of the contractile and relaxatory profiles of the commonly used graft vessels in response to major coronary vasodiladator and vasoconstrictor agents has been carried out in in vitro pharmacological investigations.The effects of noradrenaline, dopamine,6 adenosine and nitric oxide7,8 are well established, but other endogenous agents9 that increase in concentration in the circulation during cardiovascular disease are poorly studied. Leptin is a hormone secreted mostly from adipocytes, which is also produced in small amounts from other human tissues such as the heart, stomach, placenta and mammary epithelium.10-14 In addition to its essential roles in feeding behaviour and energy balance,11,12 leptin also plays an important role in many different peripheral processes, including haematopoietic, nociception, reproduction, immunity, wound healing, bone remodelling and cognitive functions.13The internal mammary artery (IMA) is the most commonly used vessel in coronary artery grafting to bypass stenosed coronary arteries. Morever its patency rate is longer lasting than the saphenous vein (SV). The IMA has a dynamic vascular bed therefore several vasoactive substances may cause contractile or dilatory responses in the IMA.Protein kinase C (PKC) is a family of serine/threonine protein kinases. It plays a critical role in the pathogenesis of many heart diseases.15-17Although it has been documented that leptin has a vasodilatatory effect,18,19 the cellular mechanism of this effect is not well documented. The aim of this study was to investigate the possible involvement of PKC-mediated mechanism(s) in the vasorelaxatory effects of sodium nitroprusside (SNP) and leptin on norepinephrine pre-contracted excised human IMA.     

Sickle cell trait is not associated with chronic kidney disease in adult Congolese patients: a clinic-based,cross-sectional study

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with significant cardiovascular (CV) and renal morbidity and mortality rates, with substantial economic burden.1,2 Therefore, early identification of CKD patients at high risk of progression is urgently needed for early and targeted treatment to improve patient care.1-3 Diabetes and hypertension are the primary risk factors for CKD and ESRD but do not fully account for CKD and ESRD risk.1-3 Marked variability in the incidence of CKD suggests that factors other than diabetes and hypertension contribute to its aetiology.4Family studies have suggested a genetic component to the aetiology of CKD and ESRD.5 In African Americans, high-risk common variants in the Apol1/MYH9 locus may explain up to 70% of the differences in ESRD rates between European and African Americans.5 While this finding has great implications for ESRD, the identification of additional risk factors for CKD, including genetic loci in association with estimated glomerular filtration rate (eGFR), may help to advance our understanding of the underpinnings of CKD in African Americans.5 In this era of identifying genetic risk factors for kidney disease, it may be appropriate to revisit one of the most common genetic disorders: sickle cell haemoglobinopathies.5In this regard, sickle cell trait (SCT), present in approximately 7–9% of African Americans, has been reported to be a potential candidate gene.6 However, conflicting reports exist as to whether SCT is a risk factor for the progression of nephropathy.6,7 Haemoglobin S (HbS) was selected for in Africa because of the protection it affords from malarial infection, a scenario similar to the protection from trypanosomal infection provided by heterozygosity for APOL1 nephropathy risk variants.6Whereas APOL1 contributes to risk for nephropathy in an autosomal recessive inheritance pattern, HbS reportedly had a dominant effect on risk, with SCT being associated with ESRD.6 In line with this finding, a few small studies on African Americans reported HbS as an independent risk factor for CKD and ESRD.8 However, other studies using a large sample of African Americans stated that SCT was not independently associated with susceptibility to ESRD in African Americans,6 highlighting the need for further studies in other populations such as those of sub-Saharan Africa where SCT is prevalent.Although SCT is very prevalent in black Africans,9 few studies have been conducted to assess the association between SCT and CKD.10 In Democratic Republic of Congo (DRC), the prevalence of CKD and SCT has been reported to be 12% and 17–24%, respectively.11-13 No study has evaluated the frequency of SCT among CKD patients to assess its association with reduced kidney function. Therefore, the aim of this clinic-based, cross-sectional study was to assess the potential association between SCT and CKD among adult Congolese patients.     

Analysis of clinical outcomes of intra-aortic balloon pump during coronary artery bypass surgery

An intra-aortic balloon pump (IABP) increases coronary blood flow and reduces left ventricular afterload.1-3 It helps to increase the necessary amount of time for heart recovery in low cardiac output syndrome following a cardiopulmonary bypass (CPB) or ischaemic events. In earlier reports, researchers had suggested that postoperative heart failure was the single indication for IABP support.1,2 However, these indications have widened, and the use of IABP support has recently become more common.Frequently reported complications of IABP include bleeding, aorto-iliac injury and thrombocytopenia.4,5 In-hospital mortality and early mortality of patients requiring IABP support is high, ranging from 26 to 50%, due to the cardiac problems that initially led to the need for this support.6,7The elderly population is continuously increasing across the globe. Parallel with this increase, the number of older patients being referred for coronary artery bypass grafting (CABG) has also increased.8 Although several studies have shown a significant increase in surgical mortality of elderly patients,9 there have been no studies regarding clinical outcomes of IABP in elderly patients.In the present study, we aimed to analyse and compare older with younger patients, regarding clinical features, postoperative complications, intensive care unit and hospital stays, and morbidity and mortality rates in patients who had undergone CABG surgery and required IABP support.     

Epidemiological African day for evaluation of patients at risk of venous thrombosis in acute hospital care settings

Acute venous thromboembolism (VTE) is a complication in patients hospitalised for a wide variety of acute medical and surgical conditions.1,2 In developed countries, VTE is the most common preventable cause of death among hospitalised patients. Over the last 30 years, extensive research has demonstrated a high risk of VTE in patients who undergo major surgery or experience severe trauma. Patients hospitalised for acute medical illness have approximately the same level of VTE risk as patients who undergo major general surgery.3-5The benefits of VTE prophylaxis are similar for both medical and moderate-risk surgical patients.6,7 VTE prophylaxis is substantially underused. There is great variation in the use of prophylaxis between countries. Even when prophylaxis is used, it may be used sub-optimally.8-10 Although some surveys and studies suggest that physicians have begun to recognise VTE as a serious health problem and use prophylaxis for at least some high-risk patients, a number of recent studies demonstrate that VTE prophylaxis remains underutilised.11-20     

Carbon monoxide poisoning increases Tpeak–Tend dispersion and QTc dispersion

Carbon monoxide (CO) poisoning may cause myocardial toxicity and life-threating cardiac arrhythmias.1-3 Acute coronary syndrome, myocardial injury, myocardial dysfunction, cardiac arrest and various types of arrhythmias have been reported in patients with acute CO poisoning.4 CO binds myocardial myoglobin and reduces myocardial oxygen reserve.5 Previous studies reported that episodes of atrial fibrillation, premature ventricular beats and sinusal tachycardia may be seen in patients with acute CO poisoning.6,7 Recent studies also suggested that risk of atrial and ventricular arrhythmia is increased in CO poisoning, due to prolonged QT_c and QT_c dispersion.2,3,8Ventricular repolarisation can be evaluated by measuring QT interval, corrected QT interval, and QT dispersion. Among these parameters, QT dispersion represents the heterogeneity of ventricular repolarisation and was clearly shown to be associated with ventricular arrhythmia.9 T_peak–T_end (T_pT_e) interval is defined as the interval between the peak point and endpoint of the T wave on surface electrocardiography and is a novel index of transmural dispersion of ventricular repolarisation.10 T_pT_e/QT ratio and T_pT_e/QT_c ratio were used in previous studies as an electrocardiographic index in the evaluation of risk of ventricular arrhythmia.11,12The effect of acute CO poisoning on QT intervals was investigated in a number of studies.2,3,8 However, to the best of our knowledge, T_pT_e interval, T_pT_e dispersion, T_pT_e/QT ratio and T_pT_e/QT_c ratio have not been investigated sufficiently in patients with CO poisoning. In this study, we aimed to investigate the effect of acute CO poisoning on electrocardiographic parameters, which indirectly show ventricular repolarisation heterogeneity. We also investigated the relationship between carboxyhaemoglobin (COHb) levels and these parameters.