Tolvaptan for Heart Failure, Systematic Review and Meta-Analysis of Trials.

The vasopressin type 2 receptor antagonist tolvaptan (TLV) is available to treat congestion in patients with heart failure. However, there is paucity of evidence guiding its use, and lack of evidence of its long-term efficacy. Our objectives are to perform a systematic review of studies examining the effects of TLV in patients with heart failure; and a quantitative meta-analysis comparing primary and secondary outcomes between TLV and placebo. Only double-blinded randomized controlled trials, with no restriction on the language or the time of publication, were included. Our main outcome measures were all-cause mortality, change in body weight, change in urine volume, and change in serum sodium. Extracted summary estimates included mean difference and SD for change in body weight, change in urine volume and change in serum sodium levels, and hazard ratio with 95% confidence interval for all-cause mortality. We found 8 double-blinded randomized controlled trials, seven of which were included in this meta-analysis. Assessment of risk of bias was conducted by investigating random sequence generation, allocation concealment, blinding, completeness of outcome data, and potential for selective reporting. We found no evidence of significant bias. TLV showed benefits in reducing body weight, increasing urine volume, and increasing serum sodium. No reduction in mortality was detected. However, the subgroup of patients with hyponatremia might have better mortality outcome with TLV. TLV seemed to be safe, as it did not cause worsening of the renal function or hypotension. In conclusion, a meta-analysis of the published literature suggests short-term benefits of TLV. However, the impact on mortality is inconclusive.

Liver transplantation at KFSHRC: achievement and challenges.

The liver transplantation program at KFSHRC has been active since 2001. More than 450 liver transplants have been performed so far. The program evolved from adult cadaveric transplant to living donor and recently to pediatric and split techniques. The 1-year survival of patients for both pediatric and adult exceeded 90% and the 5-year survival of patients is more than 80%. Associated with this success are challenges that include: organ shortage, quality of organ harvested, inability to meet the growing national need, increased demand of resource to meet the need of the program, and lack of a collaborative national strategy in organ donation and transplantation.

Liver gene expression in relation to hepatic steatosis and lipid secretion in two duck species.

The susceptibility to development of hepatic steatosis is known to differ between Muscovy and Pekin ducks. Although some experiments were conducted to decipher these differences, few data have been produced to analyse the role of specific genes in this process. For this purpose, expression levels of genes involved in lipid (ATP citrate lyase, malic enzyme 1, fatty acid synthase, stearoyl-CoA desaturase 1, diacylglycerol O-acyl transferase 2, microsomal triglyceride transfer protein, apolipoprotein A1, apolipoprotein B, sterol regulatory element binding factor 1, hepatocyte nuclear factor 4, choline/ethanolamine phosphotransferase 1, carnitine palmitoyl transferase 1A, peroxisome proliferator-activated receptor alpha and sterol O-acyltransferase) and carbohydrate (activating transcription factor 4 or cAMP-response element binding protein, mitochondrial malate dehydrogenase 2 and carbohydrate responsive element binding protein) metabolism and in other functions were analysed in the liver of Pekin and Muscovy ducks fed ad libitum or overfed. A specific positive effect of feeding was observed on the expression of genes involved mainly in fatty acids and TG synthesis and glycolysis, and negative effect on genes involved in beta-oxidation. Interestingly, a strong species effect was also observed on stearoyl-CoA desaturase 1 and to a lesser extent on diacylglycerol O-acyl transferase 2 expression, leading to large differences in expression levels between Pekin and Muscovy overfed ducks, which could explain the difference in lipid metabolism and steatosis ability observed between the two duck species. These results should shed light on gene expression that might underlie susceptibility to hepatic steatosis in humans.

Blood oxygen level-dependent (BOLD) MRI: A novel technique for the assessment of myocardial ischemia as identified by nuclear imaging SPECT.

BACKGROUND: The different levels of deoxyhemoglobin in the ischemic myocardium, induced by stressors such as dipyridamole, can be detected by blood oxygen level-dependent (BOLD) MRI and may be used to diagnose myocardial ischemia. The aim of this study was to assess the signal change in the myocardium on BOLD MRI as well as wall thickening between rest and dipyridamole stress images in ischemic and non-ischemic myocardium as identified on SPECT imaging. METHODS: Twelve patients with stress-induced myocardial ischemia on SPECT underwent rest and dipyridamole stress MRI using a double breath-hold, T2()-weighted, ECG-gated sequence to produce BOLD contrast images as well as cine-MRI for wall thickening assessment in 10 of the 12 patients. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischemic and non-ischemic myocardial segments as identified on SPECT. In each patient, two MRI slices containing 16 segments per slice were analysed. RESULTS: In total, there were 384 segments for BOLD analysis and 320 for wall thickening. For BOLD signal 137 segments correlated to segments with reversible ischemia on SPECT and 247 to normal segments, while for wall thickening 112 segments correlated to segments with reversible ischemia and 208 to normal segments. The average BOLD MRI signal intensity change was -13.8 (+/-16.3)% in the ischemic segments compared to -10.3 (+/-14.7)% in the non-ischemic segments (p=0.05). The average wall thickening was 6.4 (+/-3.4) mm in the ischemic segments compared to 8.7 (+/-3.8) mm in the non-ischemic segments (p<0.0001). CONCLUSION: Stress-induced ischemic myocardium has a different signal change and wall thickening than non-ischemic myocardium and may be differentiated on BOLD MRI. Larger studies are needed to define a threshold for detection and to determine the sensitivity and specificity of this technique.

Blood oxygen level-dependent (BOLD) magnetic resonance imaging in patients with dypiridamole induced ischaemia; a PET comparative study.

BACKGROUND: Blood oxygen level-dependent (BOLD) MRI relies on changes in deoxyhaemoglobin level in tissues under stress for signal variation and may be used for detection of ischaemic myocardium. METHODS: 15 patients with stress induced myocardial ischaemia on PET scanning underwent rest and dypiridamole stress MRI using a double breath-hold T2-weighted, ECG gated sequence to produce BOLD contrast images and cine-MRI for wall thickening assessment. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischaemic and non-ischaemic myocardial segments. RESULTS: Using PET, 156 segments were identified with reversible ischaemia and 324 as non-ischaemic. The ischaemic segments were found on BOLD MRI to have an average signal change between rest and stress of -16.7% compared to -14% in the non-ischaemic segments (p=0.04). The average wall thickening was 7.8 mm in the ischaemic segments compared with 9.5 mm in the non-ischaemic segments (p<0.0001). CONCLUSION: BOLD MRI with wall thickening assessment may differentiate ischaemic from non-ischaemic myocardium in patients with stress induced myocardial ischaemia. Larger studies with improved spatial resolution would help define a threshold for detection of ischaemia as well as determine this technique's sensitivity and specificity.

Blood oxygen level dependent (BOLD) MRI: A novel technique for the detection of myocardial ischemia.

BACKGROUND: Blood oxygen level dependent (BOLD) T2* MRI detects signal variance within the myocardium based on changes in the deoxyhaemoglobin level following pharmacological stress, and it has the potential to identify areas of myocardial ischemia. The aim of the present study was to assess the utility of BOLD T2* MRI in the detection of myocardial ischemia in patients with an existing diagnosis of coronary artery disease. METHOD: Twenty-one patients with established three-vessel coronary artery disease on coronary angiography underwent rest and dipyridamole stress MRI using a double breath-hold T2* weighted ECG gated sequence. Analysis was performed on multiple short-axis slices of the heart, projected as a bull's eye. The myocardium was divided into three coronary territories, yielding 63 territories in total. A signal change between rest and stress of more than +/-4% was significant, implying a change in deoxyhaemoglobin concentration. A signal decrease or no changes denote the presence of ischemia, while a signal increase indicates no ischemia. RESULTS: All images were of sufficient quality for signal intensity analysis. In 12/63 territories (19%), a significant signal increase following stress was detected. A significant signal decrease was detected in 34/63 territories (54%), and in 17/63 territories (27%) there was a non-significant change. The presence of a perfusion defect was identified, therefore, in 51/63 (81%), based on the signal difference between rest and stress. CONCLUSION: Changes in myocardial oxygen level appear to be detectable by BOLD T2* MRI without using contrast media. Further, larger comparative studies are required to evaluate the diagnostic and prognostic impact of this technique and to compare it to the gold standard methods for the detection of myocardial ischemia.

Unexpected result of percutaneous coronary intervention-two for the price of one.

Anomalous coronary arteries are uncommon. This case illustrates an unusual result of percutaneous coronary intervention to the right coronary artery (RCA), where the circulation was also restored in the left anterior descending artery (LAD) territory via an anomalous vessel.

Paradoxical embolism with a patent foramen ovale and atrial septal aneurysm.

Patent foramen ovale (PFO) and atrial septal aneurysm have been cited as potential risk factors for cryptogenic stroke. We present two cases which we propose to directly illustrate paradoxical embolisation as a mechanism of cerebrovascular accident. The diagnosis of PFO is discussed and the literature reviewed.

Myocardial perfusion scintigraphy: the evidence.

This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by comparison with the numbers of revascularisations and coronary angiograms performed. Furthermore, MPS activity levels in this country fall far short of those in comparable European countries, with about half as many scans being undertaken per year. Currently, the number of MPS studies performed annually in the UK is 1,200/million population/year. We estimate the real need to be 4,000/million/year. The current average waiting time is 20 weeks and we recommend that clinically appropriate upper limits of waiting time are 6 weeks for routine studies and 1 week for urgent studies.

Detection of scarred and viable myocardium using a new magnetic resonance imaging technique: blood oxygen level dependent (BOLD) MRI.

BACKGROUND: The identification of viable myocardium in patients with impaired left ventricular contraction secondary to coronary heart disease is important clinically as such myocardium is likely to benefit from revascularisation. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) relies on changes in deoxyhaemoglobin concentration under stress for signal generation and could be used for the differentiation between scarred and viable myocardium. AIM: To assess the signal change on BOLD MRI in viable and scarred myocardium as identified by positron emission tomography (PET). METHOD: 19 patients with impaired left ventricular contraction and at least one akinetic area were enrolled. They underwent rest and dipyridamole stress MRI, using a double breath hold T2* weighted, ECG gated sequence to produce BOLD contrast images, and cine-MRI for wall thickening assessment. Dynamic perfusion and metabolic PET images followed the MRI. Signal change on BOLD MRI and the wall thickening were compared between rest and stress images in hibernating and scarred segments identified by PET on two short axis slices of mid ventricle, with eight segments each. RESULTS: Using PET, 68 segments were identified as hibernating and 42 as scarred. The hibernating segments were found on BOLD MRI to have an average signal change between rest and stress of -9.53%, compared with -2.15% in the scarred segments (p = 0.008). The average wall thickening was 8.7 mm in the hibernating segments compared with 5.9 mm in the scarred segments (p < 0.0001). CONCLUSIONS: BOLD MRI with wall thickening may differentiate scarred and viable myocardium and help identify suitable patients for revascularisation. Further larger studies are needed to establish a threshold for detection, sensitivity, and specificity.

Does the presence of hibernating myocardium in patients with impaired left ventricular contraction affect QT dispersion?

BACKGROUND: Hibernating myocardium is associated with increased cardiovascular events. Increased QT dispersion on the surface electrocardiogram is a marker for serious ventricular arrhythmias. In this study, we determine whether hibernating myocardium is associated with increased QT dispersion in patients with coronary artery disease and impaired left ventricular contraction. METHODS: Positron emission tomography with (13)N-ammonia and (18)F-fluorodeoxyglucose determined the presence of metabolic-perfusion mismatch defect. QT dispersion was measured by means of a digitizing tablet with validated software. QT intervals were measured on two separate occasions by two investigators blinded to the result of the positron emission tomography scans. RESULTS: Forty-two patients with impaired left ventricular contraction were studied. They were divided into two groups: group A was made up of patients with mismatch defects (n = 26) and group B was made up of patients with no mismatch defects (n = 16). The mean (SD) QT dispersion measurements were 61.7 +/- 29.8 ms and 70 +/- 24.6 ms for groups A and B, respectively (not significant). When the patients were divided according to the dominant viability status of the impaired myocardial segment, a similar result was found. The patients whose impaired myocardium was dominantly hibernating (n = 19) had a mean QT dispersion of 66.4 +/- 31.9 ms compared with 63.6 +/- 24.8 ms in the patients whose impaired myocardium was mainly scarred (not significant). CONCLUSIONS: QT dispersion is not affected by the presence of hibernating myocardium and is therefore not clinically useful in identifying patients with this phenomenon. This is in contrast with recent reports by other groups and calls for further investigation of this dichotomy.

Can the surface electrocardiogram be used to predict myocardial viability?

OBJECTIVE: To investigate whether QRS morphology on the surface ECG can be used to predict myocardial viability. DESIGN: ECGs of 58 patients with left ventricular impairment undergoing positron emission tomography (PET) were studied. (13)N-Ammonia (NH(3)) and (18)F-fluorodeoxyglucose (FDG) were the perfusion and the metabolic markers, respectively. The myocardium is scarred when the uptake of both markers is reduced (matched defect). Reduced NH(3) uptake with persistent FDG uptake (mismatched defect) represents hibernating myocardium. First, the relation between pathological Q waves and myocardial scarring was investigated. Second, the significance of QR and QS complexes in predicting hibernating myocardium was determined. RESULTS: As a marker of matched PET defects, Q waves were specific (79%) but not sensitive (41%), with a 77% positive predictive accuracy and a poor (43%) negative predictive accuracy. The mean size of the matched PET defect associated with Q waves was 20% of the left ventricle. This was not significantly different from the size of the matched PET defects associated with no Q waves (18%). Among the regions associated with Q waves on the ECG, there were 16 regions with QR pattern (group A) and 23 regions with QS pattern (group B). The incidence of mismatched PET defects was 19% of group A and 30% of group B (NS). CONCLUSIONS: Q waves are specific but not sensitive markers of matched defects representing scarred myocardium. Q waves followed by R waves are not more likely to be associated with hibernating myocardium than QS complexes.