The Genetics of Juvenile Idiopathic Arthritis: What Is New in 2010?

Juvenile idiopathic arthritis (JIA), the most common cause of chronic arthritis in children, is believed to be influenced by genetic factors. Recent studies on the genetics of JIA have not only validated proposed genetic associations but have also led to the recognition of novel genetic associations. Studies of specific genes have been modeled on the premise of shared autoimmunity, wherein genetic variants that predispose to other autoimmune phenotypes may also confer susceptibility to JIA. The advent of genome-wide association studies has accelerated the detection of non-HLA susceptibility loci in other autoimmune phenotypes and is likely to uncover novel JIA-associated variants as well. This review highlights recent genetic investigations of JIA.     

Is Echo‐Determined Left Ventricular Geometry Associated with Ventricular Filling and Midwall Shortening in Hypertensive Ventricular Hypertrophy?

BACKGROUND: The correlation between left ventricular (LV) geometry, mass, diastolic function, and midwall fractional shortening (MFS) in hypertensive patients with left ventricular hypertrophy (LVH) is not well established owing to limited diffusion of MFS evaluation. The aim of the study was to evaluate this correlation in 1887 consecutive hypertensive patients, all affected by LVH (mean age 66 years, 924 males), with LV ejection fraction (LVEF) >45% for early detection of ventricular dysfunction rather than LVEF and diastolic function impairment. METHODS AND RESULTS: All patients underwent M-B mode echocardiography and PW-Doppler evaluation. LV geometry and mass were compared with Doppler-determined mitral flow and tissue velocities. LV geometry was eccentric (E) for 1018 subjects (53.9%) and concentric (C) for 869 (46.1%). There was no difference concerning LV diastolic dysfunction (P: n.s.) between 576 (30.6%) of the ELVH and 368 (19.4%) of the CLVH patients. The following parameters showed significant statistical differences: LV MFS impairment (P < 0.01) between 86 (4.6%) of the ELVH and 177 (9.4%) of the CLVH patients. LV MFS impairment rate was higher in 171 patients without LV diastolic dysfunction (9.1%), than in 92 patients affected (4.9%, P < 0.02). In CLVH patients, a higher prevalence of LV MFS impairment was observed in 143 without LV diastolic dysfunction (7.6%), than in 34 patients affected (1.8%, P < 0.01). In ELVH patients, a lower prevalence of LV MFS impairment was observed in 28 without diastolic dysfunction (1.5%), than in 58 patients affected (3.1%, P < 0,03). CONCLUSION: Midwall LV impairment, an independent predictor of cardiac death and morbidity in hypertensive patients, can allow early identification of patients with LV dysfunction even when LVEF or assessment of diastolic function are normal. LV MFS impairment rate is higher in CLVH patients, and even higher when considering only those CLVH patients with no diastolic dysfunction. These results suggest that the ventricular dysfunction with normal LVEF is not always due to diastolic dysfunction, but often to systolic dysfunction as assessed by MFS impairment, an important early sign of ventricular dysfunction in hypertensive patients, even when diastolic function is normal.     

Do Beta‐Blockers Impact Microvolt T‐Wave Alternans Testing in Patients at Risk for Ventricular Arrhythmias? A Meta‐Analysis

Beta‐Blockers and Microvolt T‐Wave Alternans. Introduction: Results of microvolt T‐wave alternans (MTWA) studies vary and may be influenced by whether beta‐blocker therapy was withheld prior to MTWA assessment. We conducted a meta‐analysis of the predictive value of MTWA screening for ventricular arrhythmic events in primary prevention patients with left ventricular dysfunction and examined whether results differed depending upon whether beta‐blocker use was withheld prior to MTWA testing. Methods and Results: Prospective studies that evaluated whether MTWA predicted ventricular arrhythmic events published between January 1980 and September 2008 were identified. Summary estimates for the predictive value of MTWA were derived with random‐effects models. Nine studies involving 3,939 patients were identified. Overall, an abnormal MTWA (positive and indeterminate) test was associated with an almost 2‐fold increased risk for arrhythmic events (pooled RR = 1.95, 95% CI: 1.29–2.96; P = 0.002). However, significant heterogeneity across studies was observed (P = 0.024). In the 4 studies in which beta‐blocker therapy was not withheld prior to MTWA assessment, an abnormal MTWA test was associated with a 5‐fold increased risk for arrhythmic events (pooled RR = 5.39, 95% CI: 2.68–10.84; P < 0.001) and was robust to sensitivity analyses. In contrast, the association was much weaker in those studies where the use of beta‐blocker therapy was withheld prior to MTWA testing (pooled RR = 1.40, 95% CI: 1.06–1.84; P = 0.02). Conclusions: In primary prevention patients with left ventricular dysfunction, the predictive power of MTWA varied widely, based on whether beta‐blocker therapy was withheld prior to its assessment. This observation may explain the inconsistent results of MTWA studies in this population. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1009‐1014, September 2010)     

What Is the Evidence for the Use of Botulinum Toxin in Idiopathic Detrusor Overactivity?

There is growing evidence to support the use of botulinum toxin (BTX) in idiopathic detrusor overactivity. However, BTX remains off label for this purpose. In this commentary, we review the current status of the literature discussing the evidence for efficacy and safety of BTX. In addition, we present the data regarding the preparation, dose, and administration of BTX. As an emerging treatment, high-level evidence exists for the use of BTX in patients with idiopathic detrusor overactivity; however, details about the optimum number of injection sites and injection volume remain to be answered. In addition, long-term data regarding the effect of repeated injections requires further study.     

Dispersion of the QT Interval in Subjects with Frequent Nonsustained Ventricular Arrhythmias and No Underlying Heart Disease: Arrhythmogenic Substrate or Mechanoelectrical Feedback of Arrhythmias?

Background: QT dispersion (QTd) on the ECG is thought to reflect the temporal and spatial inhomogeneity of repolarization in the underlying myocardium. In myocardial infarction, ischemia, and long QT syndromes, an increased QTd is associated with a propensity for malignant ventricular arrhythmias and sudden cardiac death. We investigated this feature of the repolarization process in subjects with frequent ventricular arrhythmias and structurally normal hearts. Methods: Forty‐nine patients referred for frequent, nonsustained ventricular arrhythmias (45 ± 14 years, ×± SD, 61% female) had normal ventricular dimensions and function, no late potentials, and normal ECG. They were compared with 30 controls (42 ± 13 years, 50% female). QTd was measured as the difference between the longest and the shortest QT in the six precordial leads at a paper speed of 50 mm/s. Results: In patients, QTc was similar to that of controls: 395 ± 21 versus 386 ± 20. However, QTd was greater: 49 ± 20 ms versus 32 ± 14 ms, P < 001. Moreover, 18 patients (36%) had QTd exceeding 60 ms—a value superior to the mean normal value of 2 SD—compared to only 1 control (3%) (P < 0.01). Finally, patients with more frequent ventricular arrhythmias had larger QTd. Conclusions: In patients with frequent nonsustained ventricular arrhythmias and otherwise normal hearts, QT interval dispersion is increased. We speculate that, instead of representing a specific electrophysiological substrate of arrhythmias, QT dispersion in this specific population could result from arrhythmias themselves through a possible mechanoelectrical feedback.     

The “Short‐Coupled” Variant of Right Ventricular Outflow Ventricular Tachycardia: A Not‐So‐Benign Form of Benign Ventricular Tachycardia?

Idiopathic ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT-VT) and idiopathic RVOT-extrasystoles are generally considered benign arrhythmias. We described three cases who originally presented with typical "benign looking" RVOT-extrasystoles or RVOT-VT but developed malignant polymorphic VT during follow-up. The unusual aspect of their RVOT-extrasystoles was their coupling interval, which appears to be intermediate between the ultra-short coupling interval of idiopathic VF and the long coupling interval seen in the truly benign RVOT-VT.     

Does Two‐Dimensional Image Reconstruction from Three‐Dimensional Full Volume Echocardiography Improve the Assessment of Left Ventricular Morphology and Function?

Aims: (i) To investigate geometric differences between apical views of the left ventricle (LV) derived from standard 2D echocardiography (std2D) and triplane (TP) views, as well as the “ideally” reconstructed 2D (rec2D) views derived from 3D full volume (3DFV) acquisitions, and their influence on the assessment of LV morphology and function. (ii) To determine the feasibility and accuracy of the automatic reconstruction of 2D apical views from 3DFV datasets. Methods and results: In 59 patients with structurally normal, dilated, and hypertrophic hearts, rec2D was reconstructed manually and automatically and compared to std2D, TP, and 3DFV regarding the image plane orientation (true vs. ideal probe position, plane intersection angles), LV dimensions, volumes, and EF. The ideal probe position deviated from the true one by 6.9 ± 4.1 mm and 9.5 ± 4.5 mm, for manually and automatically rec2D, respectively, regardless of LV geometry. The mean difference±SD between manual and automatic reconstruction was ?2.5 ± 4.4 mm. LV long axis was measured minimally, but significantly longer in rec2D than std2D and TP. LV volumes and EF did not differ between methods. The intersection angle of the two‐chamber view and the three‐chamber view with the four‐chamber view for manual and automatic reconstruction was 53°±7° and 129°±7° and 60° and 130°, respectively. Conclusion: Ideal reconstruction of nonforeshortened 2D images from 3DFV does not lead to a relevant improvement in image geometry or the assessment of LV morphology and function. The automatic reconstruction algorithm deviates only slightly from manual results.