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 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) 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.

Fibroelastoma: case report and review of the literature.

A 64 year old woman presented with right hemianaesthesia and was found to have a pansystolic apical murmur with systolic and diastolic posture related plops. Echocardiography revealed a mobile mass on the mitral valve apparatus that was confirmed by magnetic resonance imaging. This was successfully excised and was proven on histopathological examination to be a fibroelastoma. Other cases of fibroelastoma from the literature are reviewed.

Left atrial thrombus as an early consequence of blunt chest trauma.

Thromboembolism is rarely considered in discussions of the complications of blunt chest trauma. The few cases of thromboembolism that have been reported in this setting have occurred in association with significant myocardial damage. A previously fit 23 year old woman was admitted to the intensive care unit following a road traffic accident. A day later, left atrial thrombus was demonstrated by transoesophageal echocardiography in the absence of any other evidence of important myocardial injury. Anticoagulation with heparin was cautiously introduced in spite of her extensive injuries, and there were no consequent bleeding complications. At hospital discharge on day 18 she was entirely well. Full anticoagulation with warfarin was continued for a further eight weeks at which time follow up transoesophageal echocardiography showed complete resolution of the thrombus.

Changing patterns of investigation and treatment of cardiac failure in hospital.

OBJECTIVE: To assess the investigation and treatment of cardiac failure in 1995 and to compare this with management in 1992. DESIGN: Retrospective consecutive case study. SETTING: University teaching hospital. SUBJECTS: All patients (n = 265) discharged from Aberdeen Royal Infirmary in the first quarter (January 1-31 March) of 1995 with a diagnosis of congestive cardiac failure, left ventricular failure, or heart failure (unspecified). These correspond to the International Classification of Diseases 9th revision codings of 428.0, 428.1, and 428.9 respectively. METHODS: Sociodemographic and clinical data were extracted from the case notes of the above subjects and compared with similar data from the final six months of 1992. MAIN OUTCOME MEASURES: The use of echocardiography in confirming the diagnosis and delineating the aetiology of heart failure and the use of angiotensin-converting enzyme (ACE) inhibitors in the treatment of patients diagnosed as having heart failure and without contraindications to these agents. RESULTS: The number of patients discharged in 1995 with a diagnosis including cardiac failure had increased by 55.7% since 1992. The use of echocardiography had also risen from 36.6% to 72% (P < 0.0001) with an associated increase in the proportion of patients discharged on treatment with an ACE inhibitor (40% in 1992 v 55.1% in 1995: P < 0.001). The doses of ACE inhibitors used had also increased significantly (P < 0.001). Most patients with cardiac failure continue to be treated by general physicians, who are less likely to use echocardiography (P < 0.01) or prescribe an ACE inhibitor (P < 0.05) than cardiologists. CONCLUSIONS: There is increasing recognition, more thorough investigation, and improved treatment of heart failure. Despite this there are grounds for concern, both in terms of the adequacy of management and resource implications.

Prevalence of hibernating myocardium in patients with severely impaired ischaemic left ventricles.

OBJECTIVE: Severe impairment of left ventricular (LV) contraction is associated with an adverse prognosis in patients with ischaemic heart disease. Revascularisation may improve the impaired LV contraction if hibernating myocardium is present. The proportion of patients likely to benefit from this intervention is unknown. Therefore, the prevalence of hibernating myocardium in patients with ischaemic heart disease and severe impairment of LV contraction was assessed. DESIGN: From a consecutive series of patients undergoing coronary angiography for the investigation of chest pain or LV impairment, all patients with ischaemic heart disease and an LV ejection fraction (LVEF) < or = 30% were identified. These patients underwent positron emission tomography (PET) to detect hibernating myocardium, identified by perfusion metabolism mismatch. SETTING: A teaching hospital directly serving 500,000 people. RESULTS: Of a total of 301 patients, 36 had ischaemic heart disease and an LVEF < or = 30%. Twenty-seven patients had PET images, while nine patients were not imaged because of emergency revascularisation (three), loss to follow up (one), inability to give consent (four), and age < 50 years (one, ethics committee guidelines). Imaged and non-imaged groups were similar in LV impairment, demographic characteristics, and risk factor profile. Fourteen patients (52% of the imaged or 39% of all patients with ischaemic heart disease and LVEF < or = 30%) had significant areas of hibernating myocardium on PET. CONCLUSION: It is possible that up to 50% of patients with ischaemic heart disease and severely impaired left ventricles have hibernating myocardium.

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.

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.

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.

Respiratory arrest during dipyridamole stress testing.

There is an increasing usage of radionuclide scanning to assess myocardial perfusion, with dipyridamole, the most commonly used stress agent. Although this is an effective, and usually very safe, means by which to assess myocardial blood supply, there have been several incidents of acute bronchospasm in asthmatic patients. There have, however, been no previous reports of respiratory arrest occurring in patients with emphysema. This case illustrates the dangers of administering intravenous dipyridamole, or even adenosine, to patients with chronic lung disease.

Significance of the Thrombolysis in Myocardial Infarction scoring system in assessing infarct-related artery reperfusion and mortality rates after acute myocardial infarction.

Thrombolysis in Myocardial Infarction (TIMI) flow scores were originally devised as semiquantitative angiographic measures of coronary artery perfusion. Several studies have indicated an important relation between different TIMI flow grades at 90 minutes after thrombolysis and clinical outcome. To further evaluate this relation we conducted a metaanalysis of all angiographic, postinfarction trials that studied the relation between individual 90-minute TIMI flow grades and mortality rates. In 4687 pooled patients, the mortality rate was lowest in patients with TIMI grade 3 flow (3.7%) and significantly lower than those with TIMI 2 (6.6%, p = 0.0003; odds ratio 0.55; 95% confidence interval [CI] 0.4% to 0.76%) or TIMI 0/1 flow (9.2%, p < 0.0001; odds ratio 0.38; 95% CI 0.29% to 0.5%). The mortality rate difference between TIMI grade 2 and TIMI grade 0/1 patients was also significant (p = 0.02; odds ratio 0.7; 95% CI 0.51% to 0.94%). This study confirms the importance of achieving rapid and complete reperfusion after acute myocardial infarction with the best outcome associated with 90-minute TIMI 3 flow. Furthermore, it shows that although TIMI 2 flow (partial perfusion) is not equivalent to TIMI 3 flow, it nevertheless still confers a significant survival benefit compared with TIMI flow 0/1.

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.