Antonios P. Vlahos

Noninvasive assessment of pulmonary vascular resistance by Doppler echocardiography.

BACKGROUND The ratio of tricuspid regurgitation velocity (TRV) to the time-velocity integral of the right ventricular outflow tract (TVIRVOT) has been studied as a reliable measure to distinguish elevated from normal pulmonary vascular resistance (PVR). The equation TRV/TVIRVOT × 10 + 0.16 (PVRecho) has been shown to provide a good noninvasive estimate of PVR. However, its role in patients with significantly elevated PVR (> 6 Wood units [WU]) has not been conclusively evaluated. The aim of this study was to establish the validity of the TRV/TVIRVOT ratio as a correlate of PVR. The role of TRV/TVIRVOT was also compared with that of a new ratio, TRV(2)/TVIRVOT, in patients with markedly elevated PVR (>6 WU). METHODS Data from five validation studies using TRV/TVIRVOT as an estimate of PVR were compared with invasive PVR measurements (PVRcath). Multiple linear regression analyses were generated between PVRcath and both TRV/TVIRVOT and TRV(2)/TVIRVOT. Both PVRecho and a new derived regression equation based on TRV(2)/TVIRVOT: 5.19 × TRV(2)/TVIRVOT - 0.4 (PVRecho2) were compared with PVRcath using Bland-Altman analysis. Logistic models were generated, and cutoff values for both TRV/TVIRVOT and TRV(2)/TVIRVOT were obtained to predict PVR > 6 WU. RESULTS One hundred fifty patients remained in the final analysis. Linear regression analysis between PVRcath and TRV/TVIRVOT revealed a good correlation (r = 0.76, P < .0001, Z = 0.92). There was a better correlation between PVRcath and TRV(2)/TVIRVOT (r = 0.79, P < .0001, Z = -0.01) in the entire cohort as well as in patients with PVR > 6 WU. Moreover, PVRecho2 compared better with PVRcath than PVRecho using Bland-Altman analysis in the entire cohort and in patients with PVR > 6 WU. TRV(2)/TVIRVOT and TRV/TVIRVOT both predicted PVR > 6 WU with good sensitivity and specificity. CONCLUSIONS TRV/TVIRVOT is a reliable method to identify patients with elevated PVR. In patients with TRV/TVIRVOT > 0.275, PVR is likely > 6 WU, and PVRecho2 derived from TRV(2)/TVIRVOT provides an improved noninvasive estimate of PVR compared with PVRecho.

Extension of Doppler-Derived Echocardiographic Measures of Pulmonary Vascular Resistance to Patients with Moderate or Severe Pulmonary Vascular Disease

BACKGROUND Pulmonary vascular resistance (PVR) is a critical parameter in the assessment and treatment of patients with pulmonary hypertension, regardless of origin. Noninvasive estimation of PVR could be helpful. METHODS Consecutive patients with known or suggested pulmonary hypertension referred for cardiac catheterization were evaluated prospectively and the PVR was calculated invasively. Subsequently, the tricuspid regurgitation velocity (TRV), the velocity-time integral (mean of 3 measurements) of the right ventricular outflow tract (VTIm), and the right ventricular outflow tract diameter were recorded noninvasively. RESULTS The TRV/VTIm ratio and the TRV/VTIm corrected for the indexed RVOT diameter correlated well with the PVR at catheterization with R(2) = 0.711 and R(2) = 0.731, respectively, including patients with very high values of PVR. A TRV/VTI(RVOT) value of 38 provided a specificity of 100% for a PVR of 8 Woods units. CONCLUSION Noninvasive estimation is feasible over a broad range of PVR values and could be a useful tool to estimate and longitudinally tracked changes in PVR.

Provocation of Neurocardiogenic Syncope During Head-up Tilt Testing in Children: Comparison Between Isoproterenol and Nitroglycerin

OBJECTIVE. Although nitroglycerin- and isoproterenol-augmented tilt tests are of equal value in the diagnosis of neurocardiogenic syncope in adults, no data exist in children. We compared the sensitivity and specificity of the 2 tests in a pediatric population. PATITENS AND METHODS. We studied 85 patients (33 boys; mean age: 11.6 ± 2.9 years). Of them, 56 had a diagnostic history of neurocardiogenic syncope, whereas 29 served as controls. After a negative passive phase, they were randomly assigned to either intravenous isoproterenol or sublingual nitroglycerin, and tilt was continued for 20 minutes. RESULTS. Sensitivity was 0.78 for the isoproterenol test and 0.79 for the nitroglycerin test, but specificity was significantly higher for isoproterenol test compared with nitroglycerin test. In patients with a positive test, the duration of the recovery period was significantly longer after nitroglycerin (8.4 ± 2.7 minutes) than after isoproterenol (5.1 ± 1.6 minutes). CONCLUSIONS. Nitroglycerin- and isoproterenol-augmented tilt tests are associated with equal sensitivity in the diagnosis of neurocardiogenic syncope in children and adolescents. However, nitroglycerin results in more false-positive tests and produces more prolonged vasovagal symptoms. Our data do not support the routine use of nitroglycerin in the evaluation of syncope in this age group.

Changes in vascular function and structure in juvenile idiopathic arthritis

Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health.

Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21

Early detection of risk factors for enhanced primary prevention and novel therapies for treating the chronic consequences of cardiovascular disease are of the utmost importance for reducing morbidity. Recently, fibroblast growth factors (FGFs) have been intensively studied as potential new molecules in the prevention and treatment of cardiovascular disease mainly attributable to metabolic effects and angiogenic actions. Members of the endocrine FGF family have been shown to increase metabolic rate, decrease adiposity, and restore glucose homeostasis, suggesting a multiple metabolic role. Serum levels of FGFs have been associated with established cardiovascular risk factors as well as with the severity and extent of coronary artery disease and could be useful for prediction of cardiovascular death. Furthermore, preclinical investigations and clinical trials have tested FGF administration for therapeutic angiogenesis in ischemic vascular disease, demonstrating a potential role in improving angina and limb function. FGF21 has lately emerged as a potent metabolic regulator with multiple effects that ultimately improve the lipoprotein profile. Early studies show that FGF21 is associated with the presence of atherosclerosis and may play a protective role against plaque formation by improving endothelial function. The present review highlights recent investigations suggesting that FGFs, in particular FGF21, may be useful as markers of cardiovascular risk and may also serve as protective/therapeutic agents in cardiovascular disease.

Determinants of pulmonary hypertension in patients with Beta-thalassemia major and normal ventricular function.

Background/Aims: We sought to define the incidence and predictive factors of pulmonary hypertension in β-thalassemia major. Methods: We studied 27 consecutive patients (19 male, 38 ± 9 years of age) with β-thalassemia major. All the patients had normal (left and right) ventricular (systolic and diastolic) function and underwent echocardiographic assessment of pulmonary artery systolic pressure. Univariate regression and discriminant function analyses were used to identify predictive factors of pulmonary hypertension. Results: Pulmonary hypertension was observed in 18.5% of the patients, but clinically significant disease was detected in only 3.7%. A total of 14 (51.8%) patients had been receiving a combined administration of deferoxamine and deferiprone for 7.0 ± 1.3 years. Amidst a large number of variables examined, ferritin levels and delayed onset of chelation therapy were the only predictors of pulmonary hypertension. Conclusion: Pulmonary hypertension in β-thalassemia major is relatively infrequent and generally mild due to improved chelation therapy. The role of hemochromatosis in pulmonary hypertension development merits further study.

Family History of Children and Adolescents with Neurocardiogenic Syncope

We read with interest the article by Sabri et al. [4], reporting on 26 children and adolescents with neurocardiogenic syncope, previously misdiagnosed with epilepsy. Of these patients, the family history was positive for seizure in 11 patients (42%) and for syncope in 6 patients (23%). In keeping with the authors’ conclusions, we feel that the terms seizure and syncope are often used interchangeably during history taking and represent a common source of confusion. Given the frequently improper use of these terms, it appears likely that a family history positive for vasovagal symptoms might have been present in 17 (65%) of patients in the series described by Sabri et al. [4]. A family history positive for syncope is present in approximately 20% of adult patients with neurocardiogenic syncope [3], but data from pediatric patients are scarce. We examined the family history of pediatric patients with neurocardiogenic syncope (referred to our hospital between January 2002 and October 2005) and compared it to that of controls. All individuals participated in a different study and their characteristics have been described previously [5]. The presence of a positive family history in the two groups was compared using Yates’ corrected chi-square test. Seventy-six patients (32 males; mean age, 11.8±2.9 years) were diagnosed with neurocardiogenic syncope and 29 children with comparable characteristics (11 males; 11.3±2.9 years) formed the control group. A positive family history was present in 68 (89.4%) patients with neurocardiogenic syncope, more frequently (p\0.0001) than in controls (1/29; 3.4%). These data, based on our previously described patient cohort [5], have not been published or submitted for publication elsewhere. Our finding confirms previous observations in smaller series [1, 2]. Camfield et al. [1] observed a positive family history in 90% (27/30) of children with neurocardiogenic syncope, a percentage almost identical to that found in our series. Interestingly, Mathias et al. [2] reported a positive family history in 57% of patients under the age of 20 years, as opposed to 18% of patients with adult-onset symptoms. Our results, taken together with previous reports [1, 2] and the recent findings of Sabri et al. [4], suggest that a family history of vasovagal symptoms should be meticulously sought and is of value in the diagnosis of neurocardiogenic syncope in pediatric patients. This practice might prevent misdiagnosis and inappropriate initiation of antiepileptic therapy.

Serum Adipocytokine and Vascular Inflammation Marker Levels in Beta-Thalassaemia Major Patients

Background/Aim: The adipocytokines leptin and adiponectin represent a critical link between metabolism, immunity and chronic inflammation. A chronic vascular inflammatory state plays an important role in the pathophysiology of thalassaemia. We aimed to analyze the levels of these adipocytokines and determine any possible correlations with disease severity or vascular inflammation markers in beta-thalassaemia. Methods: Serum leptin, adiponectin, high-sensitivity C-reactive protein, endothelins, vascular adhesion molecule-1, intracellular adhesion molecule-1 and L- and E-selectin were measured in 28 beta-thalassaemia patients and compared with levels in healthy controls. Results: Leptin was significantly lower in patients compared to controls (2.23 ± 1.8 vs. 10.24 ± 5.78 µg/l; p = 0.0018), whereas adiponectin was elevated (11.75 ± 5.67 vs. 6.83 ± 2.75 µg/l; p = 0.009). For both adipocytokines, no correlations were found with characteristics such as age, gender, type of chelation, body mass index z score or haemoglobin. Leptin, but not adiponectin, was negatively correlated with ferritin (p = 0.032, r = –0.61). No correlations were found between leptin and the inflammation markers. However, adiponectin was positively correlated with endothelin-1 (p = 0.022, r = 0.63). Conclusions: Serum leptin is low in beta-thalassaemia, perhaps due to the toxic effect of iron overload on adipose tissue. Paradoxically, adiponectin levels are high and positively correlated with endothelin-1, raising questions about the pro- or anti-inflammatory role of this adipocytokine in beta-thalassaemia.

Selection and Presentation of Imaging Figures in the Medical Literature

Background Images are important for conveying information, but there is no empirical evidence on whether imaging figures are properly selected and presented in the published medical literature. We therefore evaluated the selection and presentation of radiological imaging figures in major medical journals. Methodology/Principal Findings We analyzed articles published in 2005 in 12 major general and specialty medical journals that had radiological imaging figures. For each figure, we recorded information on selection, study population, provision of quantitative measurements, color scales and contrast use. Overall, 417 images from 212 articles were analyzed. Any comment/hint on image selection was made in 44 (11%) images (range 0–50% across the 12 journals) and another 37 (9%) (range 0–60%) showed both a normal and abnormal appearance. In 108 images (26%) (range 0–43%) it was unclear whether the image came from the presented study population. Eighty-three images (20%) (range 0–60%) had any quantitative or ordered categorical value on a measure of interest. Information on the distribution of the measure of interest in the study population was given in 59 cases. For 43 images (range 0–40%), a quantitative measurement was provided for the depicted case and the distribution of values in the study population was also available; in those 43 cases there was no over-representation of extreme than average cases (p = 0.37). Significance The selection and presentation of images in the medical literature is often insufficiently documented; quantitative data are sparse and difficult to place in context.

14.3 Early cardiovascular risk assessment in patients with juvenile idiopathic arthritis

Background Inflammation has emerged as an important factor that contributes to the development of atherosclerosis and is associated with increased cardiovascular risk. Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition with its origin in childhood. Its adult form, rheumatoid arthritis, has been associated with an excess of cardiovascular disease even after adjustment for traditional risk factors.