Right atrial and ventricular strain detects subclinical changes in right ventricular function in precapillary pulmonary hypertension.

Right ventricular (RV) ejection fraction (EF) by cardiac magnetic resonance (CMR) correlates to outcome in precapillary pulmonary hypertension (pPH) patients, but is insensitive to early changes. Strain might provide incremental information. In this study, we compare right atrial (RA) and RV strain in pPH patients to healthy controls, and evaluate the prognostic value of strain in pPH. In this cross-sectional study, 45 pPH patients and 20 healthy controls underwent CMR, and feature-tracking derived RA and RV strain were evaluated. pPH patients had impaired RA reservoir and conduit strain, and RV longitudinal strain (LS), compared to healthy controls. In pPH patients with preserved RVEF (≥ 50%, n = 18), RA reservoir (35% ± 9 vs. 41% ± 6, p = 0.02) and conduit strain (16% ± 8 vs. 23% ± 5, p = 0.004), and RV-LS (-25% ± 4 vs. -31% ± 4, p < 0.001) remained impaired, compared to healthy controls. The association of strain with the primary endpoint (combination of all-cause death, lung transplantation, and heart failure hospitalization) was evaluated using a multivariable Cox regression model. RV-LS (HR 1.18, 95%-CI 1.04-1.34, p = 0.01) and RA strain (reservoir: HR 0.87, 95%-CI 0.80-0.94, p = 0.001; conduit: HR 0.85, 95%-CI 0.75-0.97, p = 0.02, booster: HR 0.81, 95%-CI 0.71-0.92, p = 0.001) were independent predictors of outcome, beyond clinical and imaging features. In conclusion, pPH patients have impaired RA strain and RV-LS, even when RVEF is preserved. In addition, RA strain and RV-LS were independent predictors of adverse prognosis. These results emphasize the incremental value of RA and RV strain analyses, to detect alterations in RV function, even before RVEF declines.

[Spondylodiscitis as a rare manifestation of gout]. / Spondylodiscitis als zeldzame manifestatie van jicht.

BACKGROUND: Spondylodiscitis is usually caused by microorganisms, but there are also non-infectious causes. CASE DESCRIPTION: We are describing an 84-year-old man with severe pain in the side and elevated inflammation parameters. MRI of the spinal column yielded a picture suggesting spondylodiscitis. Repeated peripheral cultures and culture of a vertebral biopsy did not yield a pathogen. Intravenous antibiotics had no effect on symptoms or inflammation parameters. When the physical examination was repeated, we found arthritis in the feet and tophi. Microscopic examination of a new vertebral biopsy found urate crystals. This meant we were dealing with spondylodiscitis as manifestation of gout. Treatment with colchicine was highly successful. CONCLUSION: Spinal column gout is unknown, but seems to occur with some regularity. This disease can be symptom-free but may also lead to myelopathy or spondylodiscitis. In case of spondylodiscitis without demonstrated pathogen in patients with gout or risk factors for this, the vertebral biopsy should be evaluated for urate crystals or a dual-energy CT should be considered.

ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans.

BACKGROUND: High-density lipoprotein (HDL) exerts a variety of anti-atherothrombotic functions, including a potent anti-inflammatory impact. In line, the direct pro-inflammatory effects of C-reactive protein (CRP) can be attenuated by HDL in vitro. OBJECTIVE: To evaluate whether this also holds true in humans, we assessed the ability of reconstituted HDL to neutralize CRP-mediated activation of coagulation and inflammation. METHODS: Fifteen healthy male volunteers received an infusion of recombinant human (rh)CRP (1.25 mg kg(-1) body weight). In eight of these volunteers, an infusion of human apoAI reconstituted with phosphatidylcholine (apoAI-PC; 80 mg kg(-1) body weight) preceded rhCRP infusion. RESULTS: Infusion of rhCRP alone elicited an inflammatory response and thrombin generation. In individuals who received apoAI-PC prior to rhCRP, these effects were abolished. Parallel tests in primary human endothelial cells showed that apoAI-PC preincubation with rhCRP abolished the CRP-mediated activation of inflammation as assessed by IL-6 release. Although we were able to show that rhCRP co-eluted with HDL after size-exclusion chromatography, plasmon surface resonance indicated the absence of a direct interaction between HDL and CRP. CONCLUSION: Infusion of apoAI-PC prior to rhCRP in humans completely prevents the direct atherothrombotic effects of rhCRP. These findings imply that administration of apoAI-PC may offer benefit in patients with increased CRP.

Sustained changes in lipid profile and macrophage migration inhibitory factor levels after anti-tumour necrosis factor therapy in rheumatoid arthritis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) has recently emerged as an important cytokine possibly linking rheumatoid arthritis (RA) and atherogenesis. Because atherogenesis is accelerated in RA this study was conducted to investigate whether anti-tumour necrosis factor (TNF) therapy could lead to sustained downregulation of systemic MIF levels and improvement in lipid profiles. METHODS: Fifty RA patients with active disease (disease activity score in 28 joints (DAS28) >or=3.2), who started adalimumab therapy at 40 mg every other week, were included. At baseline, weeks 16 and 52 serum levels of MIF and lipids were assessed. In addition, the DAS28 and serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were determined. RESULTS: After 16 weeks of adalimumab therapy, both DAS28 and MIF levels were significantly decreased (p<0.001 and p = 0.020, respectively). This was sustained up to week 52 (p<0.001 and p = 0.012, respectively). CRP levels and ESR were significantly reduced after 16 and 52 weeks of adalimumab therapy (p<0.001). High-density lipoprotein cholesterol levels increased at week 16 (p<0.001), but returned to baseline at week 52. Apolipoprotein (apo) A-I levels increased at week 16 (p<0.001) and remained stable (p = 0.005). This resulted in an improved apo B/A-I ratio. CONCLUSIONS: The results underline the sustained downregulation of MIF as a potential new mechanism by which anti-TNF therapy might reduce vascular inflammation, and as such perhaps cardiovascular morbidity in RA patients. This hypothesis is supported by an improved apo B/A-I ratio as well as reduced CRP levels in these patients.

Systemic inflammation as a risk factor for atherothrombosis.

Several chronic inflammatory disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and chronic infections that are associated with a chronic inflammatory state, such as human immunodeficiency virus (HIV) infection, are associated with an increased incidence of cardiovascular disease (CVD). Cardiovascular mortality is a major cause of death in patients with these disorders. Direct effects and indirect sequelae of systemic inflammation promote atherothrombotic vascular disease. Pathophysiological processes promoting atherogenesis can initiate years before the diagnosis of a chronic inflammatory disease is made, and since exposure to risk factors in this pre-clinical phase is widespread, early cardiovascular protection in these patients seems warranted.

Atherogenesis in rheumatology.

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.

Gradients of epicardial strain across the perfusion boundary during acute myocardial ischemia.

To study the mechanical interaction between acutely ischemic and adjacent perfused myocardium, nonhomogeneous distributions of end-systolic epicardial strain were measured using an array of radiopaque beads sewn on the left ventricular free wall of the pig during complete left circumflex coronary artery occlusion. The midwall perfusion boundary, demarcated by postmortem dye injection, was reconstructed over the span of the epicardial array. During ischemia, circumferential and longitudinal shortening remained significantly depressed up to 13 mm outside the ischemic region near the base of the ventricle, up to 8-9 mm at the midventricle, but only 0-1 mm near the apex (P < 0.05). Gradients of circumferential and longitudinal strain across the boundary were significantly different during both baseline conditions and acute ischemia (P = 0.0001). However, gradients of the change in the strain from baseline to ischemia were not different for the two components. These results support the concept that direction-dependent differences in the strain gradients across the boundary during ischemia were due to the preservation of the baseline regional variations of strain combined with a loss of systolic function in the ischemic region.

Intramuscular pressure varies with depth. The tibialis anterior muscle studied in 12 volunteers.

Pressures in the tibialis anterior muscle were recorded at rest and during exercise with transducer-tipped catheters in 12 volunteers while they were supine or standing. The recordings were repeated with venous stasis created by an inflated tourniquet cuff on the thigh. Catheters were placed at 3 different sites in the muscle: catheter I adjacent to the deep surface of the fascia over the anterior compartment; catheter II between the fascia and the central tendon; and catheter III deep in the muscle close to the interosseous membrane. In both the supine and standing positions the intramuscular pressure at rest and the muscle relaxation pressure during exercise, obtained by catheter II, were greater than the corresponding pressures measured by the superficially located catheter I in the normal as well as in the volume loaded limb. The same conditions for pressure measurement consistently revealed lower pressures recorded by catheter III compared to II, but the difference was not significant. Our results indicate that intramuscular pressure increases centripetally, as the centrally lying tendon is approached. We conclude that pressure measurements for diagnosis of acute and chronic compartment syndromes and in ergonomic studies should be based on recordings from a standard location of the catheter within the muscle and a standard posture of the subject.