Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients.

OBJECTIVE: Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups. METHODS: The study involved 25 ERA patients (female/male 21/4; mean age 52.04 +/- 14.05 years; disease duration

Aetiology and antibiotic resistance patterns of urinary tract infections in the elderly: a 6-month study.

Urinary tract infections (UTIs) are a common cause of bacteraemia in the elderly and are associated with a high probability of hospitalization. Despite the impact of UTIs on health status and quality of life, a limited number of studies have evaluated their aetiology in this population. This study aimed to evaluate the microbial aetiology and pattern of susceptibility of bacteria causing UTIs in the elderly. For this purpose, a retrospective cohort study of elderly residents (n = 472, aged >65 years) in 14 nursing homes in Milan (Italy) and its province was performed. Globally, 393 micro-organisms from 328 samples were isolated: Escherichia coli was the most prevalent (44.8 %), followed by Proteus mirabilis (20.4 %), Providencia spp. (8.9 %), Klebsiella spp. (6.4 %) and Pseudomonas aeruginosa (4.6 %). Enterococci were the most frequently isolated Gram-positive organisms (7.4 %). Almost all Enterobacteriaceae were susceptible to nitrofurantoin, carbapenems and amikacin. Extended-spectrum ß-lactamases were detected in 42.1 % of isolates. The most active antibiotics against P. aeruginosa were colistin, amikacin and piperacillin/tazobactam. All Gram-positive organisms were susceptible to glycopeptides and linezolid, and 90 % were susceptible to nitrofurantoin. Fluoroquinolones showed a limited activity against all the tested micro-organisms. Escherichia coli remains the major micro-organism responsible for UTIs in older people, although to a lesser extent than in a younger population. The high rates of resistance observed in this study make careful use of antibiotics advisable to limit further development of resistance.

Detection of preclinical impairment of myocardial function in rheumatoid arthritis patients with short disease duration by speckle tracking echocardiography.

BACKGROUND: Subclinical cardiac involvement diagnosis is important for long term management of rheumatoid arthritis (RA) patients. Recently, 2D speckle tracking echocardiography (STE) allows non invasive and angle-independent measurement of left ventricular (LV) dimensions and regional myocardial strain (ε). The aim of this study was to assess whether STE can be useful to detect subclinical cardiac involvement in RA patients. METHODS: We studied 22 RA patients (10 M, 12 F, aged 46 ± 12 years) without clinical evidence of coronary artery disease (CAD) and 20 healthy controls matched for age and sex by STE. LV end-systolic longitudinal and radial ε from apical 4-chamber view were analyzed using available software (QLAB 6.0). RESULTS: Standard echo and Doppler parameters did not differ between the 2 groups. Tissue Doppler Imaging (TDI) showed a significant reduction of S', E' and E'/A' ratio from the basal septum and lateral mitral annulus in RA patients. LV end-systolic radial and longitudinal ε of basal-lateral, basal- and mid-septal, mid-lateral and apical segments were significantly reduced compared to controls. CONCLUSIONS: Our data indicate that LV end-systolic radial and longitudinal ε are reduced in RA patients without CAD despite normal standard echo. Non invasive evaluation of LV function by STE appears to be useful to detect subclinical cardiac involvement in comparison to conventional 2D echoDoppler, representing a promising new modality to follow-up RA patients for cardiac involvement.

Coronary flow reserve and asymmetric dimethylarginine levels: new measurements for identifying subclinical atherosclerosis in patients with psoriatic arthritis.

OBJECTIVE: To identify the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) and healthy controls using intima-media thickness (IMT), coronary flow reserve (CFR), and the plasma concentration of asymmetric dimethylarginine (ADMA), to evaluate the correlations among ADMA, IMT, and CFR. METHODS: The study involved 22 patients who fulfilled the ClASsification of Psoriatic ARthritis study group criteria for PsA and a cohort of 35 healthy controls with no history or current signs of coronary artery disease (CAD). Common carotid IMT was measured using high-resolution B-mode ultrasonography. Dipyridamole transthoracic stress echocardiography was used to evaluate CFR. Blood samples were obtained to assess ADMA levels. The clinical manifestations were recorded. All patients were treated with disease-modifying antirheumatic drug, but none had received any biological or steroid therapy. RESULTS: Plasma ADMA levels were significantly higher in the patients with PsA (0.71 ± 0.07 µmol/l vs 0.48 ± 0.07 µmol/l; p = 0.00) and CFR was significantly reduced in that group (2.86 ± 0.70 vs 3.3 ± 0.43; p < 0.01) compared to controls. Common carotid IMT was greater in the patients with PsA, but the difference was not significant (0.64 ± 0.26 mm vs 0.62 ± 0.5 mm; p = 0.65). There was a significant correlation between CFR and plasma ADMA levels in the PsA group (R = 0.28; p < 0.01), but no correlation between plasma ADMA levels and IMT (R = 0.02; p = 0.32), Disease Activity Score 28 (p = 0.52), or Psoriasis Area and Severity Index (p = 0.98). CONCLUSION: Our patients with PsA showed a profile of subclinical atherosclerosis. ADMA may be a useful marker of endothelial dysfunction in PsA.

Robotic treadmill training improves cardiovascular function in spinal cord injury patients.

BACKGROUND: Body weight supported treadmill training (BWSTT) assisted with a robotic driven gait orthosis (DGO) is an emerging tool in rehabilitating patients with lost sensorimotor function. Few information about the effects of BWSTT on cardiovascular system are available. The purpose of this study was to determine the effects of BWSTT on: 1) left ventricular (LV) systo-diastolic function; 2) coronary flow reserve (CFR); 3) endothelial function in patients with lost sensorimotor function due to neurologic lesions. METHODS: Fourteen adults (males 10, age 50.6±17.1years) with motor incomplete spinal cord injuries (SCI) due to trauma or spondylotic diseases underwent standard echocardiographic examination, non invasive assessment of CFR by dipyridamole stress echo and determination of plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 6weeks of BWSTT. RESULTS: At post training evaluation we observed lower LV end-diastolic (P=0.0164) and end-systolic volumes (P=0.0029) with increased ejection fraction (EF) (P=0.0266). We also observed a LV interventricular septum (IVS) (P=0.00469) increase. At the same time, we detected an improvement of LV diastolic function as witnessed by the reduction of isovolumic relaxation time (IVRT) (P=0.0404) and deceleration time (DT) (P=0.0405) with an increased E/A ratio (P=0.0040). Improved CFR (P=0.020) and reduced plasma ADMA levels (P=0.0005) have been observed too, in association with a reduction of the inflammatory status (C-reactive protein (CRP) (P=0.0022) and erythrocyte sedimentation rate (ESR) (P=0.0005)). CONCLUSION: For the first time, this study demonstrated that 6weeks of BWSTT improved not only the sensorimotor function but also systo-diastolic LV function, CFR and endothelial dysfunction associated with a reduction of the inflammatory status in patients with incomplete SCI.

Speckle tracking echocardiography: A new approach to myocardial function.

Echocardiography is the most common diagnostic method for assessing cardiac function but some limitations affect this technique. Until now, visual assessment of wall motion and thickening has allowed only a subjective evaluation of myocardial function and requires long-term training. Recently, new echocardiographic techniques have been introduced to evaluate myocardial mechanics. Tissue Doppler imaging (TDI) technique is limited by angle-dependency such that only deformation along the ultrasound beam can be derived from velocities, while myocardium deforms simultaneously in three dimensions. Speckle tracking echocardiography (STE) is a more recent technique that provides a global approach to left ventricular myocardial mechanics, giving information about the three spatial dimensions of cardiac deformation. In this editorial, we describe the physical and pathophysiological concepts of STE, discussing the differences compared to TDI and underlining the pitfalls of this new technique.

Role of cardiovascular imaging in systemic autoimmune diseases.

Systemic autoimmune diseases are characterized by an excess of cardiovascular (CV) morbidity and mortality compared to the general population, mainly due to chronic inflammation that promotes the development of endothelial dysfunction and enhanced atherosclerosis. Early diagnosis of silent CV involvement is mandatory to improve the long term prognosis of these patients and CV imaging provides valuable information as a reliable diagnostic tool. Transthoracic echocardiography, with several applications (e.g. coronary flow reserve evaluation, tissue Doppler imaging, speckle tracking and the transesophageal approach), represents a first line evaluation, in association with biomarkers of endothelial dysfunction, such as asymmetric dimethylarginine. Nuclear medicine provides useful information on myocardial perfusion. The aim of this editorial is to provide a brief but complete review of the diagnostic tools available for screening and follow up of CV involvement in systemic autoimmune diseases.

The heart in rheumatoid arthritis.

Morbidity and mortality rates are higher in rheumatoid arthritis (RA) patients than in the general population. Many studies have shown that coronary artery disease is one of the most common causes of death in RA and seems to occur at a younger age than in the general population. RA per se is as much a cardiovascular (CV) risk factor as diabetes, arterial hypertension and dyslipidemia etc., and so it is necessary to plan a follow-up using the same diagnostic and therapeutic approaches as those commonly used for primary and secondary prevention in non-RA patients at high CV risk. All of the cardiac structures can be affected during the course of RA (valves, the conduction system, the myocardium, endocardium and pericardium, and the coronary arteries), and cardiac complications include a variety of clinical manifestations. As these are all associated with an unfavourable prognosis, it is essential to detect subclinical cardiac involvement in still asymptomatic RA patients in order to assure adequate long-term treatment.

Usefulness of cardiovascular biomarkers and cardiac imaging in systemic rheumatic diseases.

Systemic rheumatic diseases (SRDs) are associated with accelerated atherosclerosis. It has recently been recognised that chronic inflammation is an important factor in the development of atherosclerotic plaque and endothelial dysfunction. The levels of biomarkers such as serum pentraxin 3 (PTX3), an innate immunity protein, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, are higher in SRD  patients with cardiovascular (CV) disease and are now recognized as new CV risk factors. Many diagnostic methods and imaging techniques detect subtle pre-clinical CV abnormalities in SRD patients, although their clinical significance has not yet been established in patients. Echocardiographic examinations based on the evaluation of coronary flow reserve (CFR), tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) seem to be the most suitable means of screening and diagnosis. Furthermore, plasma ADMA levels could be used as a simple means of screening SRD patients at higher CV risk who need more aggressive treatment aimed at slowing or reversing the progression of atherosclerosis.

The effect of pharmacological therapy on the cardiovascular system of patients with systemic rheumatic diseases.

The higher mortality rate among rheumatoid arthritis (RA) patients in comparison with the general population is largely attributable to cardiovascular (CV) disease, particularly coronary atherosclerosis, but also non-fatal myocardial infarction and heart failure. It may be due to RA-specific risk factors such as hyperhomocysteinemia, disease-related dyslipidemia or vascular inflammation, or morbidity related to high levels of cytokines such as tumour necrosis factor (TNF) and RA medications. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most important in rheumatology, but many are associated with CV disease. A number of randomised control trials have shown that, although exposure to low doses of corticosteroids for 1-3years does not significantly increase CV risk, longer exposure can increase CV events. The use of disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, increases homocysteinemia, reduces inflammation and improves lipid profiles, thus reducing the development of atherosclerosis and clinically overt CVD. Although contraindicated in RA patients with severe heart failure, biological agents such as anti-TNF agents delay and even reverse the progression of endothelial dysfunction and atherosclerosis. Tocilizumab leads to changes in lipid profiles without increasing adverse vascular events. The effects on the CV system depend on the drug itself, the dose and the period of exposure, and so CV risk should be evaluated before starting treatment with any drug.

Cardiac involvement in systemic rheumatic diseases: An update.

The high rates of cardiovascular (CV) mortality and morbidity observed in patients with systemic autoimmune diseases (SADs) cannot be fully explained by traditional atherosclerosis risk factors as standard therapy (i.e. corticosteroids and methotrexate), cytokines and disease activity may all contribute to accelerated atherosclerosis. There is considerable evidence showing that chronic inflammation and immune dysregulation play a pathogenetic role in the development of atherosclerosis in patients with SADs. Chronic inflammation, accelerated atherosclerosis and functional abnormalities of the endothelium suggest that subclinical CV involvement begins soon after the onset of the disease and progresses with disease duration. All cardiac structures may be affected during the course of SADs (valves, the conduction system, the myocardium, endocardium and pericardium, and coronary arteries), and the cardiac complications have a variety of clinical manifestations. As these are all associated with an unfavourable prognosis, it is essential to detect subclinical cardiac involvement in asymptomatic SAD patients, and begin adequate management and treatment early.

Subclinical impairment of coronary flow velocity reserve assessed by transthoracic echocardiography in young renal transplant recipients.

BACKGROUND: In renal transplant recipients (RTR) an increased risk to develop cardiovascular injury is present. Transthoracic Doppler echocardiographic assessment of coronary flow velocity reserve (CFVR), a sensitive and minimally invasive technique, was recently employed to detect both macrovascular and microvascular coronary artery disease (CAD) in different clinical settings. The prevalence of coronary involvement in young adult RTR is still unknown. The aim of the study was to investigate the presence of early cardiovascular damage in asymptomatic young adult RTR. METHODS: Transthoracic Doppler echocardiographic-derived CFVR and common carotid intima-media thickness (IMT) were assessed in 25 asymptomatic young adult RTR (mean age 25.7+/-7.0 years; range 17.3-43.9) without CAD and 25 healthy controls. RESULTS: CFVR was lower in young adult RTR compared to controls (2.8+/-0.6 vs. 3.5+/-0.8; P<0.001), meanwhile left ventricular wall motion and common carotid IMT were comparable in both groups. We found a negative correlation between CFVR and age (r=-0.50; P=0.018) and months on dialysis (r=-0.54; P<0.01). CONCLUSIONS: Young adult RTR showed a reduced CFVR reflecting an impaired coronary microcirculation, which is significantly related to the age and duration of dialysis; coronary microvascular damage is detectable in the absence of changes in common carotid IMT. Non-invasive evaluation of CFVR by transthoracic stress echocardiography could be a reliable method for identification of early coronary microvascular involvement in young adult RTR.

Cardiovascular involvement in systemic autoimmune diseases.

Autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS), systemic sclerosis and systemic vasculitis, affect a large number of people in whom one of the leading causes of morbidity and mortality is cardiovascular disease. Cardiovascular disease is associated with the development of accelerated atherosclerosis. It seems to occur at a younger age than in the general population, is often asymptomatic and, in addition to traditional risk factors, also involves specific risk factors as chronic inflammation, the duration and activity of the autoimmune disease, and immunosuppressive therapy. The early phases of cardiovascular involvement in patients with autoimmune diseases may be clinically silent, with only a microcirculation disorder present. There are various means of detecting morphological cardiac damage: coronary angiography remains the gold standard for diagnosing coronary stenosis, but new, non invasive and more reliable methods have been introduced into clinical practice in order to detect subclinical microcirculation abnormalities.