François P. Sarasin

Prospective evaluation of patients with syncope: a population-based study.

Abstract Purpose To determine the diagnostic yield of a standardized sequential evaluation of patients with syncope in a primary care teaching hospital. Patients and methods All consecutive patients who presented to the emergency department with syncope as a chief complaint were enrolled. Their evaluation included initial and routine clinical examination, including carotid sinus massage, as well as electrocardiography and basic laboratory testing. Targeted tests, such as echocardiography, were used when a specific entity was suspected clinically. Other cardiovascular tests (24-hour Holter monitoring, ambulatory loop recorder ECG, upright tilt test, and signal-averaged electrocardiography) were performed in patients with unexplained syncope after the initial steps. Electrophysiologic studies were performed in selected patients only as clinically appropriate. Follow-up information on recurrence and mortality were obtained every 6 months for as long as 18 months for 94% (n = 611) of the patients. Results After the initial clinical evaluation, a suspected cause of syncope was found in 69% (n = 446) of the 650 patients, including neurocardiogenic syncope (n = 234, 36%), orthostatic hypotension (n = 156, 24%), arrhythmia (n = 24, 4%), and other diseases (n = 32, 5%). Of the 67 patients who underwent targeted tests, suspected diagnoses were confirmed in 49 (73%) patients: aortic stenosis (n = 8, 1%), pulmonary embolism (n = 8, 1%), seizures/stroke (n = 30, 5%), and other diseases (n = 3). Extensive cardiovascular workups, which were performed in 122 of the 155 patients in whom syncope remained unexplained after clinical assessment, provided a suspected cause of syncope in only 30 (25%) patients, including arrhythmias in 18 (60%), all of whom had abnormal baseline ECGs. The 18-month mortality was 9% (n = 55, including 8 patients with sudden death); syncope recurred in 15% (n = 95) of the patients. Conclusion The diagnostic yield of a standardized clinical evaluation of syncope was 76%, greater than reported previously in unselected patients. Electrocardiogram-based risk stratification was useful in guiding the use of specialized cardiovascular tests.

Living donor liver transplantation for early hepatocellular carcinoma: a life expectancy and cost-effectiveness perspective

Cadaveric liver transplantation (CLT) is an excellent treatment for early hepatocellular carcinoma (HCC). Its use, however, is limited by the shortage of grafts, with up to 30% of patients developing contraindications to the procedure while waiting for a donor. Living donor liver transplantation (LDLT) has emerged as an alternative to overcome this limitation. We compared the consequences of LDLT versus CLT using a Markov model balancing the gains and losses in life expectancy among donors and recipients. For a 60-year-old recipient with a 70% 5-year survival after transplantation, a 4% monthly drop-out rate, and a donor with 1% mortality, LDLT became more effective than CLT after 3.5 months on the waiting list. These results varied with the probability of developing contraindications to transplantation, the survival after transplantation, and the donors mortality. For a 12-month delay saved on the waiting list, the gain in survival provided by LDLT compared with CLT ranged between 0 and 2.8 life years depending on survival after transplantation, time spent on the waiting list, and drop-out rate. LDLT was cost-effective (less than

A Risk Score to Predict Arrhythmias in Patients with Unexplained Syncope

50,000 per quality-adjusted life year saved) in all scenarios of waiting lists exceeding 7 months, and this figure ranged from 2 to 16 months when varying the drop-out rate. LDLT for early HCC offered substantial gains in life expectancy with acceptable cost-effectiveness ratios when the waiting list exceeds 7 months. The gain in life expectancy and the cost-effectiveness of LDLT were more dependent on the drop-out rate and the outcome after transplantation than on donors mortality.

IV N-Acetylcysteine and Emergency CT: Use of Serum Creatinine and Cystatin C as Markers of Radiocontrast Nephrotoxicity

OBJECTIVES To develop and validate a risk score predicting arrhythmias for patients with syncope remaining unexplained after emergency department (ED) noninvasive evaluation. METHODS One cohort of 175 patients with unexplained syncope (Geneva, Switzerland) was used to develop and cross-validate the risk score; a second cohort of 269 similar patients (Pittsburgh, PA) was used to validate the system. Arrhythmias as a cause of syncope were diagnosed by cardiac monitoring or electrophysiologic testing. Data from the patients history and 12-lead emergency electrocardiography (ECG) were used to identify predictors of arrhythmias. Logistic regression was used to identify predictors for the risk-score system. Risk-score performance was measured by comparing the proportions of patients with arrhythmias at various levels of the score and receiver operating characteristic (ROC) curves. RESULTS The prevalence of arrhythmic syncope was 17% in the derivation cohort and 18% in the validation cohort. Predictors of arrhythmias were abnormal ECG (odds ratio [OR]: 8.1, 95% confidence interval [CI]=3.0 to 22.7), a history of congestive heart failure (OR: 5.3, 95% CI=1.9 to 15.0), and age older than 65 (OR: 5.4, 95% CI=1.1 to 26.0). In the derivation cohort, the risk of arrhythmias ranged from 0% (95% CI=0 to 6) in patients with no risk factors to 6% (95% CI=1 to 15) for patients with one risk factor, 41% (95% CI=26 to 57) for patients with two risk factors, and 60% (95% CI = 32 to 84) for those with three risk factors. In the validation cohort, these proportions varied from 2% (95% CI=0 to 7) with no risk factors to 17% (95% CI=10 to 27) with one risk factor, 35% (95% CI=24 to 46) with two risk factors, and 27% (95% CI=6 to 61) with three risk factors. Areas under the ROC curves ranged from 0.88 (95% CI=0.84 to 0.91) for the derivation cohort to 0.84 (95% CI=0.77 to 0.91) after cross-validation within the same cohort and 0.75 (95% CI=0.68 to 0.81) for the external validation cohort. CONCLUSIONS In patients with unexplained syncope, a risk score based on clinical and ECG factors available in the ED identifies patients at risk for arrhythmias.

Preventing stroke recurrence in patients with patent foramen ovale: Antithrombotic therapy, foramen closure, or therapeutic abstention? A decision analytic perspective

OBJECTIVE The purpose of this study was to assess the effect of i.v. administration of N-acetylcysteine (NAC) on serum levels of creatinine and cystatin C, two markers of renal function, in patients with renal insufficiency who undergo emergency contrast-enhanced CT. SUBJECTS AND METHODS Eighty-seven adult patients with renal insufficiency who underwent emergency CT were randomized to two groups. In the first group, in addition to hydration, patients received a 900-mg injection of NAC 1 hour before and another immediately after injection of iodine contrast medium. Patients in the second group received hydration only. Serum levels of creatinine and cystatin C were measured at admission and on days 2 and 4 after CT. Nephrotoxicity was defined as a 25% or greater increase in serum creatinine or cystatin C concentration from baseline value. RESULTS A 25% or greater increase in serum creatinine concentration was found in nine (21%) of 43 patients in the control group and in two (5%) of 44 patients in the NAC group (p = 0.026). A 25% or greater increase in serum cystatin C concentration was found in nine (22%) of 40 patients in the control group and in seven (17%) of 41 patients in the NAC group (p = 0.59). CONCLUSION On the basis of serum creatinine concentration only, i.v. administration of NAC appears protective against the nephrotoxicity of contrast medium. No effect is found when serum cystatin C concentration is used to assess renal function. The effect of NAC on serum creatinine level remains unclear and may not be related to a renoprotective action.

Upper-Respiratory Viral Infection, Biomarkers, and COPD Exacerbations

Emphasis on the role of patent foramen ovale as a potential risk factor for ischemic paradoxical stroke has recently increased. Current therapeutic options for secondary stroke prevention include long-term antithrombotic therapies and invasive closure of the defect, but selective indications have not been evaluated. Therefore we developed a Markov-based decision analysis model for a hypothetical cohort of patients 55 years of age with presumed paradoxical embolism, measuring for each therapy the risks of stroke recurrence, treatment-related complications, and death after 5 years and the quality-adjusted life-years. Over a wide range of stroke risk recurrence (0.8% per year to 7% per year), the gain provided by closure of the defect exceeded the one obtained by other therapeutic options. When the risk exceeded 0.8% per year and 1.4% per year, respectively, this was also verified for anticoagulation and antiplatelet therapies compared with therapeutic abstention. Therapeutic abstention was the preferred strategy under 0.8% per year. Sensitivity analyses identified key parameters influencing the choice of therapy. These included estimates of stroke recurrence, bleeding rates, surgery-related case fatality rates, and age. Considering the risks of treatment and the devastating consequences of a recurrent stroke, our model suggests that if the estimated risk of paradoxical stroke recurrence is > 0.8% per year, therapeutic abstention becomes the worst option. Above this threshold secondary stroke prevention with anticoagulation therapy or surgical closure of the defect is the preferred strategy, and assessment of both the risk of stroke recurrence and the risk related to therapeutic options should guide individual therapeutic decision making.

How to Prevent Stroke Recurrence in Patients with Patent Foramen ovale: Anticoagulants, Antiaggregants, Foramen Closure, or Nothing?

Background Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear. The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated. Methods The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD. Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition. Results Eighty-six patients (mean age, 72 years; male, 64%) were included. During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three. A dual infection was present in three patients. After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase). In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up. During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection. Conclusions Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract. In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others. Trial registration clinicaltrials.gov; Identifier: NCT00448604.

Is measurement of d-dimer useful in the diagnosis of cerebral venous thrombosis?

Several studies found a significant association between patent foramen ovale (PFO), interatrial septal aneurysm, and patients less than 60 years of age presenting with acute stroke and without any identified coexisting mechanism explaining the acute event. Paradoxical embolism from a venous source through a right-to-left shunt is usually incriminated, but the definite proof for paradoxical embolism is often lacking, with screening for deep-venous thrombosis leading to variable estimates. Despite these controversies, the-possibility of paradoxical embolism in patients with cryptogenic stroke and PFO is commonly retained as the cause of the neurological deficit. Moreover, there are now definite studies documenting that these patients are at risk of recurrence. The aim of the present paper is to review the literature on the risks of stroke recurrence in patients with atrial septal defects, and to weigh the risks and benefits of the different therapeutic options currently available to prevent stroke recurrence. These options include chronic oral anticoagulant or antiplatelet therapy, and more invasive procedures such as surgical closure or transcatheter closure of the defect. Finally, using the principles of decision analysis, the authors suggest tentative practical therapeutic recommendations that might be helpful to clinicians in daily practice.

Decision analysis model of prolonged oral anticoagulant treatment in factor V Leiden carriers with first episode of deep vein thrombosis.

Background: The diagnosis of cerebral venous thrombosis (CVT) is a challenge because its clinical presentation is variable, brain CT may be normal, and MRI is not always available. Furthermore, early treatment may be effective. As d-dimer (DD) measurement is a sensitive test for the exclusion of venous thromboembolism, the authors studied whether this test could be useful in the diagnosis of CVT. Methods: A prospective study of 54 consecutive patients with headaches suggestive of CVT was conducted between October 2000 and September 2002. DD levels were tested for all patients in the emergency room before brain CT or MRI was performed. Results: Twelve (22%) of the 54 patients had CVT, and 10 (83%) of these 12 patients had DD level of >500 ng/mL (sensitivity of 83% and negative predictive value of 95%). Two patients with confirmed CVT and DD of <500 ng/mL had a history of chronic headache of >30 days’ duration. In the 42 patients without confirmed CVT, only 4 patients had DD level of >500 ng/mL (specificity of 90% and positive predictive value of 71%). Conclusions: DD test is useful in the diagnosis of acute CVT. A value below 500 ng/mL makes acute thrombosis unlikely.

Screening of Illegal Intracorporeal Containers (“Body Packing”): Is Abdominal Radiography Sufficiently Accurate? A Comparative Study with Low-Dose CT

Objective: To assess the risks and benefits of oral anticoagulant treatment extended beyond 3 months after a first episode of deep vein thrombosis in patients who carry factor V Leiden mutation. Such patients have over twice the risk of recurrence after the recommended treatment period, but more information is required before widespread genetic screening can be recommended. Design: A decision analysis Markov model (with data extracted form literature) representing the risks of developing symptomatic venous thromboembolism, the risks of major bleeding, and the efficacy of anticoagulant treatment. Subjects: A hypothetical cohort of 1000 carriers of factor V Leiden recovering from a first episode of deep vein thrombosis in the lower limbs. Main outcome measures: Risks and benefits of, firstly, stopping oral anticoagulation 3 months after first episode of thrombosis with reinitiation of treatment only after recurrent thrombosis and, secondly, extension of oral anticoagulation up to 1 to 5 years. Results: Despite consistent biases in favour of extended oral anticoagulation, analysis revealed that among factor V carriers the number of major haemorrhages induced by oral anticoagulants would exceed that of clinical pulmonary emboli prevented over the entire range of duration of anticoagulation (1 to 5 years). On the other hand, the number of recurrent deep vein thrombi prevented would exceed that of iatrogenic major bleedings. Conclusion: The lack of evidence of a net clinical benefit of prolonged oral anticoagulation, at least beyond 1 year, among patients recovering from acute deep vein thrombosis does not support the decision to promote widespread genetic screening programmes to detect the factor V mutation. Key messages Patients who carry the factor V Leiden mutation have a more than twice the risk of recurrence after a first episode of deep vein thrombosis Before screening for the abnormality is advocated in all patients recovering from acute deep vein thrombosis, it should be determined whether carriers of the mutation would benefit from the diagnosis The risks (major haemorrhage) of extended oral anticoagulation beyond the usually recommended 3 month period would exceed its benefits, in terms of clinical pulmonary emboli prevented The decision to promote widespread screening programmes to detect factor V mutation should be questioned in the absence of clinical benefit provided by extended use of oral anticoagulants