2007 annual research and education meeting of the Spondyloarthritis Research and Therapy Network (SPARTAN)

OBJECTIVE: The Spondyloarthritis Research and Therapy Network (SPARTAN; www.spartangroup.org) was founded in 2003 by a group of North American clinicians and researchers to promote research, education, and treatment of spondyloarthritis (SpA). In past years, it has produced and disseminated United States-specific modifications of the ASsessments in Ankylosing Spondylitis (ASAS) guidelines for the use of anti-tumor necrosis factor (TNF) therapy in AS1,2. SPARTAN held its fifth annual research meeting in September 2007 in Cleveland, Ohio. Highlights of the meeting included updates on current research in SpA, including epidemiology and genetics, bone formation and inflammation, biomarkers, activation of the IL-23/IL-17 axis, and animal models. A presentation was made on basic and clinical science of inflammatory bowel disease, and an educational pre-meeting conference was specifically designed for rheumatology fellows.     

Ventricular high-rate episodes in pacemaker diagnostics identify a high-risk subgroup of patients with tachy-brady syndrome.

OBJECTIVES: The purpose of this study was to evaluate the frequency and clinical significance of ventricular high-rate (VHR) episodes (ventricular rate >162 bpm) in patients with symptomatic bradycardia and paroxysmal atrial fibrillation (AF). BACKGROUND: Newer pacemakers have enhanced diagnostic features that permit detection and storage of detailed information about the frequency, duration, and time of onset of multiple episodes of AF, atrial tachycardia (AT), and ventricular tachycardia (VT). However, the prevalence and prognostic value of AF associated with rapid ventricular rates in the pacemaker population are unknown. METHODS: We prospectively followed 125 patients who received a Medtronic AT 500/501 pacemaker for symptomatic bradycardia and paroxysmal AF. RESULTS: AF recurred in 112 patients (90%) during 22 +/- 8 months of follow-up. A total of 1,324 VHR episodes occurred in 38 patients (30%). Episodes with available electrograms (n = 560) were reviewed and classified as AF (n = 279; 50%), AT (n = 266; 47%) or VT (n = 15; 3%). AF burden was higher in patients with VHR episodes (median 1.9 vs 0.2 hours/day; P < .001). After controlling for AT/AF burden and heart disease, VHR episodes were a significant independent predictor of hospitalization for cardiovascular symptoms (odds ratio 2.92, 95% confidence interval 1.33-6.38; P = .007). Heart rate control improved over time in the cohort, and the frequency of VHR episodes decreased during follow-up (P < .001). CONCLUSIONS: VHR episodes documented in the pacemaker diagnostics identify a high-risk subgroup of patients with AF. Monitoring VHR episodes may be useful for identifying pacemaker patients with AF who require more vigilant monitoring, additional investigations, and/or additional interventions.     

Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

To determine whether a functional type II receptor of transforming growth factor β (TGF-β) is required to mediate the growth inhibitory effect of TGF-β on the skin in vivo, we have generated transgenic mice that overexpress a dominant negative-type II TGF-β receptor (ΔβRII) in the epidermis. The ΔβRII mice exhibited a thickened and wrinkled skin, and histologically the epidermis was markedly hyperplastic and hyperkeratotic. In vivo labeling with BrdUrd showed a 2.5-fold increase in the labeling index over controls, with labeled nuclei occurring in both basal and suprabasal cells of transgenic epidermis. In heterozygotes, this skin phenotype gradually diminished, and by 10–14 days after birth the transgenic mice were indistinguishable from their normal siblings. However, when F₁ mice were mated to homozygosity, perinatal lethality occurred due to the severe hyperkeratotic phenotype, which restricted movement. Cultured primary keratinocytes from ΔβRII mice also exhibited an increased rate of growth in comparison with nontransgenic controls, and were resistant to TGF-β-induced growth inhibition. These data document the role of the type II TGF-β receptor in mediating TGF-β-induced growth inhibition of the epidermis in vivo and in maintenance of epidermal homeostasis.     

Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix remodeling involving atrial fibrosis and atrial dilatation. Angiotensin II mediated pathways and matrix metalloproteinases (MMPs) have been implicated in these processes. Our aim was to study atrial structural remodeling and the expression of the angiotensin receptor subtypes and MMPs and their inhibitors (TIMPs) in patients with mitral valve disease with and without AF. METHODS AND RESULTS: Biopsies from right and left atrial appendages (RA and LA) were taken from patients undergoing CABG (n=9, all in sinus rhythm (SR)) or mitral valve surgery (MVS; n=19; 9 with permanent AF and 10 in SR). Patients with MVS and AF had significantly larger atria (versus MVS and SR: p=0.02; versus CABG: p<0.01). The MVS patients had significantly more fibrosis than the control CABG group. Fibrosis was increased in both the AF and SR MVS groups in the LA, but only in the MVS-AF group in the RA. These AF patients had significantly more tricuspid regurgitation than SR patients. MMP-1 was down-regulated in LA of MVS patients (p=0.02) independent of the underlying rhythm (SR or AF; p=0.95). In RA biopsies, MMP-1 was down-regulated only in the MVS and AF group. MMP-9 was down-regulated in the MVS patients compared to CABG both in the RA and LA, and without a difference between the SR and AF groups. Protein expression of AT-1, AT-2, MMP-2, TIMP-1, -2 and -4, TNF-alpha, and TNF-alpha-converting enzyme did not differ significantly between the 3 groups. CONCLUSIONS: Concordant changes between MMP-expression and fibrosis during mitral valve disease, both in LA and RA, suggest involvement of MMPs in structural atrial remodeling. AF itself did not contribute to altered fibrosis or MMP-expression in the LA. The association between AF and RA changes may be precipitated by greater hemodynamic load due to tricuspid regurgitation in these patients.     

Oxygen Desaturation in Daily Life and During a Laboratory-Based Protocol of Activities of Daily Living in COPD: Is There Relationship?

Purpose

To analyze the relationship between oxygen desaturation episodes during a laboratory-based ADL protocol and in real-life routine in patients with stable chronic obstructive pulmonary disease (COPD).

Methods

Twenty patients with stable COPD (12 men, 70 ± 7 years, FEV₁% 54 ± 15 predicted) with no indication for long-term oxygen therapy (LTOT) were submitted to assessments including ADL performance by the Londrina ADL Protocol (LAP) and level of physical activity in daily life, both while submitted to simultaneous activity and pulse oximeter monitoring.

Results

Episodes of desaturation ≥ 4% (ED ≥ 4%) during the LAP were correlated both with ED ≥ 4% in daily life (r = 0.45) and number of episodes of SpO₂ under 88% (ED < 88%) in daily life (r = 0.59). ED < 88% during the LAP was also correlated with ED < 88% in daily life (r = 0.51), explaining 43% of its variance.

Conclusion

In stable patients with COPD and no indication of LTOT, episodes of desaturation during a lab-based ADL protocol are moderately related to episodes of desaturation in daily (real) life, especially those episodes under 88%.

     

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume.