Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis.

OBJECTIVES: This study analyzed the accuracy of gadolinium-enhanced cardiovascular magnetic resonance (CMR) for the diagnosis of cardiac sarcoidosis (CS). BACKGROUND: The diagnosis of CS was made according to the guidelines of the Japanese Ministry of Health and Welfare (1993); CMR has not been incorporated into the guidelines, and the diagnostic accuracy of CMR for the diagnosis of CS has not yet been evaluated. METHODS: We performed an analysis of 12-lead electrocardiograms (ECGs), 24-h ambulatory ECGs, echocardiograms, thallium scintigrams, and gadolinium-enhanced CMR studies in 58 biopsy-proven pulmonary sarcoidosis patients assessed for CS. The diagnostic accuracy of CMR for CS was determined using modified Japanese guidelines as the gold standard. RESULTS: The diagnosis of CS was made in 12 of 58 patients (21%); CMR revealed late gadolinium enhancement (LGE), mostly involving basal and lateral segments (73%), in 19 patients. In 8 of the 19 patients, scintigraphy was normal, while patchy LGE was present. The sensitivity and specificity of CMR were 100% (95% confidence interval, 78% to 100%) and 78% (95% confidence interval, 64% to 89%), and the positive and negative predictive values were 55% and 100%, respectively, with an overall accuracy of 83%. CONCLUSIONS: In patients with sarcoidosis, CMR is a useful diagnostic tool to determine cardiac involvement. New diagnostic guidelines should include CMR.

Reproducibility of nitrate-stimulated tilt testing in patients with suspected vasovagal syncope and a healthy control group.

OBJECTIVE: Nitrate-stimulated tilt testing may be used to diagnose vasovagal syncope or to guide therapy. To date, the reproducibility of the test in patients with clinically suspected vasovagal syncope and healthy controls is undetermined. A high reproducibility is a prerequisite for correct interpretation of the test result. This study investigates the reproducibility of a nitrate-stimulated tilt test in patients with clinically suspected vasovagal syncope and a healthy control group. METHODS AND RESULTS: We studied 43 patients (24 women, 19 men) with a typical history of vasovagal syncope and 18 healthy controls (3 women, 15 men). We used a combined tilt protocol with a 30-minute passive and 15-minute nitrate-stimulated phase. The second tilt test was performed 16 +/- 12 days after the first. In both patients and controls, overall positive tilt responses were reproduced in the second test in 100%. In contrast to this, the reproducibility of an overall negative test was 50% in patients but 93% in controls. Overall hemodynamic responses to tilt were reproducible in 80%. CONCLUSION: Nitrate-stimulated tilt testing in both patients with suspected vasovagal syncope and controls has an excellent reproducibility of positive results but a moderate reproducibility of negative results. Importantly, these results are still valid at a repeat interval of 2 weeks and longer. These data suggest that in patients with suspected vasovagal syncope, a nitrate-stimulated tilt test may provide a suitable tool to evaluate the efficacy of a therapeutic approach.

Cardiac involvement in patients with pulmonary sarcoidosis assessed at two university medical centers in the Netherlands.

STUDY OBJECTIVES: We aimed to determine cardiac involvement in patients with pulmonary sarcoidosis (PS) followed up at two university medical centers in the Netherlands. DESIGN: We reviewed the findings in consecutive patients assessed by our departments during 1998 to 2004, and classified them as patients who had presented with symptoms of cardiac sarcoidosis (CS) [group A], and those who had been screened for this condition (group B). SETTING: Two university medical centers in the Netherlands. PATIENTS: One hundred one patients (69 men [mean age, 47.6 years] and 32 women [mean age, 47.3 years]) with biopsy-proven PS. INTERVENTIONS: Twelve-lead ECG (n = 101), ambulatory ECG (n = 74), echocardiography (n = 80), (201)Tl single-photon emission CT (n = 61), cardiac MRI (n = 87), coronary angiography to exclude coronary artery disease (n = 17), and endomyocardial biopsy (n = 9). MEASUREMENTS: ECG, structural, and functional cardiac abnormalities according to the modified guidelines of the Japanese Ministry of Health and Welfare (1993). RESULTS: Sixteen of 19 patients in group A and 3 of 82 patients in group B received a diagnosis of CS. During a mean follow-up of 1.7 years (range, 3 months to 4 years), four patients in group A died (20%) and nine patients received a pacemaker and/or an implantable cardioverter-defibrillator (47%), while the patients in group B had an uncomplicated course. CONCLUSIONS: Once symptomatic CS develops in PS patients, the prognosis becomes very grim. In contrast, the prognosis in asymptomatic cardiac involvement in PS patients is good. Considering the poor prognosis of symptomatic CS, pulmonologists should consider regular screening of their PS patients for cardiac involvement with straightforward detection methods.

Nitrate-stimulated tilt testing enhances the predictive value of the tilt test on the risk of recurrence in patients with suspected vasovagal syncope.

OBJECTIVE: Nitrate-stimulated tilt testing may be used to diagnose vasovagal syncope and to guide therapy. However, to date the predictive value of the test is undetermined. This study analyses the risk of recurrence of syncope in vasovagal patients on the basis of a nitrate-stimulated tilt result and other clinical factors. METHODS AND RESULTS: We used a combined passive and nitrate-stimulated tilt protocol. One year after the test a questionnaire, asking about recurrence of syncope and other demographic factors, was sent to 131 patients. Passive tilting was found not to be a useful predictor; recurrence rates after a positive and negative test were 26% and 30%, respectively, and non-significant. With the addition of sublingual nitrates the test became a significant predictor; recurrence rates were 34 (34%) with a positive and 4 (13%) with a negative tilt test (p = 0.031). Univariate analysis of the clinical factors revealed that gender and pre-test symptomatology were significant predictors of recurrence. Multivariate analysis revealed no additional relationships. CONCLUSION: In patients with suspected vasovagal syncope, a positive tilt test with sublingual nitrates together with the clinical factors gender and symptomatology, are predictors for recurrence of syncope during one year of follow-up. Without specific therapy the prognosis of vasovagal syncope is good.

Predicting capacities required in cardiology units for heart failure patients via simulation.

The management of a department of cardiology has to plan the capacity of both elective and non-elective patients. Heart failure (HF) patients are admitted to the hospital in a non-elective way. The precision with which the capacity needed for non-elective patients can be predicted determines the degree of flexibility in planning the admission of elective patients. In this study we want to determine how accurately we can predict the bed occupancy of HF patients using a simulation model. Data of the year 2000 were used to obtain the necessary probability distribution functions. Data from the year 2001 were used for determining the prediction accuracy. The results show that the arrival of new HF patients can be adequately predicted. However, the bed occupancy by new and especially current patients is predicted less accurately. Still in 70% (90%) of the days of a 5-day-prediction interval the error is at most one (two) bed(s). The results may improve if the cardiologist is asked to predict the length of stay of the current patients.

Search for haplotype interactions that influence susceptibility to type 1 diabetes, through use of unphased genotype data.

Type 1 diabetes is a T-cell-mediated chronic disease characterized by the autoimmune destruction of pancreatic insulin-producing beta cells and complete insulin deficiency. It is the result of a complex interrelation of genetic and environmental factors, most of which have yet to be identified. Simultaneous identification of these genetic factors, through use of unphased genotype data, has received increasing attention in the past few years. Several approaches have been described, such as the modified transmission/disequilibrium test procedure, the conditional extended transmission/disequilibrium test, and the stepwise logistic-regression procedure. These approaches are limited either by being restricted to family data or by ignoring so-called "haplotype interactions" between alleles. To overcome this limit, the present study provides a general method to identify, on the basis of unphased genotype data, the haplotype blocks that interact to define the risk for a complex disease. The principle underpinning the proposal is minimal entropy. The performance of our procedure is illustrated for both simulated and real data. In particular, for a set of Dutch type 1 diabetes data, our procedure suggests some novel evidence of the interactions between and within haplotype blocks that are across chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 15, 16, 17, 19, and 21. The results demonstrate that, by considering interactions between potential disease haplotype blocks, we may succeed in identifying disease-predisposing genetic variants that might otherwise have remained undetected.

Systematic review of the outcome of aortic valve replacement in patients with aortic stenosis.

BACKGROUND: After the establishment of aortic valve replacement procedure for aortic stenosis, there are heterogeneous studies and varying reports on outcome. An analysis that compares individual studies to summarize the overall effect is still lacking. This study systematically analyzes the change in left ventricular (LV) mass index and ejection fraction after aortic valve replacement in adult patients. METHODS: We performed MEDLINE and bibliographic searches and included 27 articles published between 1980 and 2003 about the outcome of valve replacement in 1546 aortic stenosis patients. To allow comparisons, we stratified the patients into early (0-6 months), intermediate (7-24 months), and late (25-120 months) follow-up groups for the analysis of both LV mass regression and ejection fraction. We separately analyzed five articles that reported groups of patients with low preoperative ejection fraction. RESULTS: Increase in ejection fraction after surgery is more pronounced in the patients that have low preoperative ejection fraction (28% +/- 4.3%(preop) vs 40% +/- 9.4%(6-41 months) follow-up). Patients with normal or high preoperative ejection fraction have variable outcomes. However, regression of LV mass is uniformly achieved regardless of age, sex, time of operation, or types of valve substitute. Furthermore, LV mass regresses predominantly within the first 6 months after surgery (g/m2, 181 +/- 25.8(preop) vs 124 +/- 27(6 months), 117 +/- 15(24 months), and 113 +/- 14(120 months) follow-up). CONCLUSIONS: This systematic review supports the concept that aortic stenosis patients with LV dysfunction show a clear functional improvement after aortic valve replacement. Ventricles regress rapidly and reach their approximate final size within the first 6 months of surgery.

Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism.

OBJECTIVES: We sought to investigate the role of fibroblast growth factor (FGF)-1 during acute myocardial ischemia and reperfusion. BACKGROUND: The FGFs display cardioprotective effects during ischemia and reperfusion. METHODS: We investigated FGF-1-induced cardioprotection during ischemia and reperfusion and the intracellular signaling pathways responsible for these effects in an ex vivo murine setup of myocardial ischemia and reperfusion. RESULTS: Cardiac-specific human FGF-1 overexpression was associated with enhanced post-ischemic hemodynamic recovery and decreased lactate dehydrogenase release during reperfusion. Inhibition of the FGF receptor, protein kinase C (PKC), and tyrosine kinase (TK) resulted in blockade of FGF-1-induced protective effects on cardiac functional recovery and cell death. CONCLUSIONS: The overexpression of FGF-1 induces cardioprotection through a pathway that involves the FGF receptor, PKC, and TK.